A novel source of biologically active compounds - The leaves of Serbian herbaceous peonies.

In order to gain further insight into how various extraction techniques (maceration, microwave-, and ultrasound-assisted extractions) affect the chemical profile and biological activities of leaf extracts from Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L., this research was performed. The targeted chemical characterization of the extracts was achieved using the Ultra-High-Performance-Liquid-Chromatography-Linear-Trap-Mass-Spectrometry OrbiTrap instrumental technique, while Fourier Transform Infrared Spectroscopy was conducted to investigate the structural properties of the examined leaf extracts. According to the results, the species P. officinalis, Bozurna locality as the origin of the plant material, and microwave-assisted extraction produced the maximum polyphenol yield, (491.9 ± 2.7 mg gallic acid equivalent (GAE)/mL). The ethanolic extracts exhibited moderate antioxidant activity as evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and phosphomolybdenum tests. With MIC values of 0.125 mg/mL, the leaf extracts produced by ultrasound-assisted extraction and maceration (Deliblato sands and Bogovo gumno) had the best antibacterial activity against Pseudomonas aeruginosa and Salmonella Typhimurium. Ultrasound-assisted extraction has proven to produce the most effective antimicrobial agents. Inhibitory potential towards glucosidase, amylase, cholinesterases, and tyrosinase was evaluated in enzyme inhibition assays and molecular docking simulations. Results show that leaves of P. tenuifolia L. obtained by ultrasound-assisted extraction had the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity. Namely, the complexity of the polyphenol structures, the extraction method, the used locality, and the different mechanisms of the reactions between bioactives from leaf extracts and other components (free radicals, microorganisms, and enzymes) are the main factors that influence the results of the antioxidant tests, as well as the antibacterial and enzyme-inhibitory activities of the extracts. Hydroxymethyl-phenyl pentosyl-hexoside and acetyl-hydroxyphenyl-hexoside were the first time identified in the leaf extract of the Paeonia species. Due to their proven biological activities and the confirmed existence of bioactive compounds, leaf extracts may find use in foodstuffs, functional foods, and pharmaceutical products.

Lignin based microspheres for effective dyes removal: Design, synthesis and adsorption mechanism supported with theoretical study.

Multifunctional lignin bio-based adsorbent, b-LMS, was obtained via inverse copolymerization in the suspension of acryloyl modified kraft lignin (KfL-AA) and bio-based trimethylolpropane triacrylate (bio-TMPTA). Morphological and structural characterization of KfL-AA and b-LMS was performed using BET, FTIR, Raman, NMR, TGA, SEM, and XPS techniques. The b-LMS microspheres with 253 ± 42 µm diameters, 69.4 m2 g-1 surface area, and 59% porosity efficiently adsorb Malachite Green (MG), Tartrazine (T), and Methyl Red (MR) dye. The influence of pH, pollutant concentration, temperature, and time on the removal efficiency was studied in a batch mode. Favorable and spontaneous processes with high adsorption capacities e.g. 116.8 mg g-1 for MG, 86.8 mg g-1 for T, and 68.6 mg g-1 for MR indicate the significant adsorptive potential of b-LMS. Results from diffusional and single mass transfer resistance studies indicate that pore diffusion is a rate-limiting step. Theoretical calculations confirmed a higher affinity of b-LMS to cationic dye MG compared with an anionic and neutral one, i.e. T and MR, respectively. The data fitting from a flow system, using semi-empirical equations and Pore Surface Diffusion Modelling (PSDM) provided breakthrough point determination. The results from the desorption and competitive adsorption study proved the exceptional performance of b-LMS. Moreover, sulfation of b-LMS, i.e.production of b-LMS-OSO3H, introduced high-affinity sulfate groups with respect to cationic dye and cations. Developed methodology implements the principle of sustainable development and offers concept whose results contribute to the minimization of environmental pollution.

Lignin Microspheres Modified with Magnetite Nanoparticles as a Selenate Highly Porous Adsorbent.

Highly porous lignin-based microspheres, modified by magnetite nanoparticles, were used for the first time for the removal of selenate anions, Se(VI), from spiked and real water samples. The influence of experimental conditions: selenate concentration, adsorbent dosage and contact time on the adsorption capacity was investigated in a batch experimental mode. The FTIR, XRD, SEM techniques were used to analyze the structural and morphological properties of the native and exhausted adsorbent. The maximum adsorption capacity was found to be 69.9 mg/g for Se(VI) anions at pH 6.46 from the simulated water samples. The modified natural polymer was efficient in Se(VI) removal from the real (potable) water samples, originated from six cities in the Republic of Serbia, with an overage efficacy of 20%. The regeneration capacity of 61% in one cycle of desorption (0.5 M NaOH as desorption solution) of bio-based adsorbent was gained in this investigation. The examined material demonstrated a significant affinity for Se(VI) oxyanion, but a low potential for multi-cycle material application; consequently, the loaded sorbent could be proposed to be used as a Se fertilizer.

Hybrid material based on subgleba of mosaic puffball mushroom (Handkea utriformis) as an adsorbent for heavy metal removal from aqueous solutions.

The alkali treated subglebal tissue of the mosaic puffball (Handkea utriformis) (Sa) and Sa modified with hydroxyapatite (Sa-HAp), obtained by successive ionic layer adsorption and reaction (SILAR) method, were used for the removal of Pb2+, Cd2+ and Ni2+ from aqueous solution. The materials were characterized by FT-IR, Raman, SEM and EDS analysis and by determination of pHPZC. The adsorption performances of Sa and Sa-HAp were assessed in batch experiments at different pH, contact times, temperatures and mass of the adsorbent. Different models of adsorption isotherms were used, and the best fit was obtained with the Langmuir model. Maximum adsorption capacities of Sa towards Pb2+, Cd2+ and Ni2+ were 44.82, 15.54 and 17.21 mg g-1, while for Sa-HAp were 79.55, 52.59 and 45.01 mg g-1, respectively. Kinetic data were well fitted by a pseudo second-order model, while thermodynamic studies disclose spontaneous and endothermic adsorption process. The Sa-Hap was successfully regenerated with 1 M NaCl and after the fifth desorption cycle and 10 h achieved 82.9, 69.7 and 60.4 %, while for 0.5 M NaCl + 0.5 M NaOH and 1 h was 78.3, 64.1, 57.5 % of desorbed Pb2+, Cd2+ and Ni2+, respectively. The competitive study and results from a column system confirmed good applicability of Sa-HAp adsorbent.

Synthesis, characterization and SAR studies of bis(imino)pyridines as antioxidants, acetylcholinesterase inhibitors and antimicrobial agents.

In this study we synthesized a series of sixteen bis(imino)pyridines (BIPs) starting from 2,6-diaminopyridine and various aromatic aldehydes, and evaluated their antioxidant, antibacterial, antifungal and acetylcholinesterase (AChE) inhibitory activity. The chemical structures were elucidated by FTIR, elemental analysis, ESR and HRMS. 1H and 13C NMR spectra couldn't be acquired due to the formation of stable, carbon-centered radical cations in a solution, as confirmed by ESR spectroscopy and DFT calculations. The in vitro antioxidant potency was evaluated using four assays: free radical scavenging activity (DPPH and ABTS), reducing power and total antioxidant capacity assay. BIPs demonstrated excellent antioxidant properties, and two derivatives proved to be more potent than reference antioxidants (ascorbic acid and Trolox) in all assays. DFT calculations on ωB97XD/6-311++g(d,p) level of theory provided valuable insights into the radical scavenging mechanism of BIPs. For hydroxyl-substituted BIPs, hydrogen atom transfer (HAT) is a predominant mechanism, while the single electron transfer coupled with proton transfer (SET-PT) governs the antioxidant activity of other derivatives. Intramolecular hydrogen bonding (IHB) plays an important role in the mechanism of antioxidant activity as revealed by noncovalent interaction analysis and rotational barrier calculations. The spin density of radical cations is localized on carbon atoms of a pyridine ring, which corroborates with g-factors and multiplicity obtained from ESR analysis. The most potent BIP exhibited moderate inhibitory activity toward AChE (IC50 = 20 ± 4 µM), while molecular docking suggested binding at the peripheral anionic site of AChE with the MMFF94 binding enthalpy of -43.4 kcal/mol. Moderate in vitro antimicrobial activity of BIPs have been determined against several pathogenic bacterial strains: Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus and clinical isolate of methicillin resistant S. aureus (MRSA). The antifungal activity of BIPs toward Candida albicans was also confirmed. The similarity ensemble approach combined with molecular docking suggested leucyl aminopeptidase as the probable antimicrobial target for the three most potent BIP derivatives.

Linear IgA dermatosis of the childhood-Report of an amoxicillin-induced case.

Linear IgA dermatosis (LAD) is a rare autoimmune disorder in children. A 9-year-old boy was presented with blisters on the intact skin (face, body, arms, hands, soles, perigenital and perianal area) after amoxicillin treatment. Systemic corticosteroids and dapsone treatment for 6 weeks was successful. Clinical and immunofluorescence examinations are most important for differentiation of LAD and other drug-induced bullous dermatoses. They enable an early introduction of proper therapy.

Efficient multistep arsenate removal onto magnetite modified fly ash.

The modification of the fly ash (FA) by magnetite (M) was performed to obtain FAM adsorbent with improved adsorption efficiency for arsenate removal from water. The novel low cost adsorbents are characterized by liquid nitrogen porosimetry (BET), scanning electron microscopy (SEM), X-ray diffraction (XRD), Mössbauer spectroscopy (MB) and Fourier transform infrared (FTIR) spectroscopy. The optimal conditions and key factors influencing the adsorbent synthesis are assessed using the response surface method (RSM). The adsorption experiment was carried out in a batch system by varying the contact time, temperature, pH, and mass of the adsorbent. The adsorption capacity of the FAM adsorbent for As(V), calculated by Langmuir model, was 19.14 mg g-1. The thermodynamic parameters showed spontaneity of adsorption with low endothermic character. The kinetic data followed the pseudo-second-order kinetic model (PSO), and Weber-Morris model indicated intra-particle diffusion as rate limiting step. Alternative to low desorption capability of the FAM was found by five consecutive adsorption/magnetite precipitation processes which gave exhausted layered adsorbent with 65.78 mg g-1 capacity. This research also has shed light on the mechanism of As(V)-ion adsorption, presenting a promising solution for the valorization of a widely abundant industrial waste.

Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis.

Pathological fibrosis is driven by a feedback loop in which the fibrotic extracellular matrix is both a cause and consequence of fibroblast activation. However, the molecular mechanisms underlying this process remain poorly understood. Here we identify yes-associated protein (YAP) (homolog of drosophila Yki) and transcriptional coactivator with PDZ-binding motif (TAZ) (also known as Wwtr1), transcriptional effectors of the Hippo pathway, as key matrix stiffness-regulated coordinators of fibroblast activation and matrix synthesis. YAP and TAZ are prominently expressed in fibrotic but not healthy lung tissue, with particularly pronounced nuclear expression of TAZ in spindle-shaped fibroblastic cells. In culture, both YAP and TAZ accumulate in the nuclei of fibroblasts grown on pathologically stiff matrices but not physiologically compliant matrices. Knockdown of YAP and TAZ together in vitro attenuates key fibroblast functions, including matrix synthesis, contraction, and proliferation, and does so exclusively on pathologically stiff matrices. Profibrotic effects of YAP and TAZ operate, in part, through their transcriptional target plasminogen activator inhibitor-1, which is regulated by matrix stiffness independent of transforming growth factor-ß signaling. Immortalized fibroblasts conditionally expressing active YAP or TAZ mutant proteins overcome soft matrix limitations on growth and promote fibrosis when adoptively transferred to the murine lung, demonstrating the ability of fibroblast YAP/TAZ activation to drive a profibrotic response in vivo. Together, these results identify YAP and TAZ as mechanoactivated coordinators of the matrix-driven feedback loop that amplifies and sustains fibrosis.

Matrix stiffness reverses the effect of actomyosin tension on cell proliferation.

The stiffness of the extracellular matrix exerts powerful effects on cell proliferation and differentiation, but the mechanisms transducing matrix stiffness into cellular fate decisions remain poorly understood. Two widely reported responses to matrix stiffening are increases in actomyosin contractility and cell proliferation. To delineate their relationship, we modulated cytoskeletal tension in cells grown across a physiological range of matrix stiffnesses. On both synthetic and naturally derived soft matrices, and across a panel of cell types, we observed a striking reversal of the effect of inhibiting actomyosin contractility, switching from the attenuation of proliferation on rigid substrates to the robust promotion of proliferation on soft matrices. Inhibiting contractility on soft matrices decoupled proliferation from cytoskeletal tension and focal adhesion organization, but not from cell spread area. Our results demonstrate that matrix stiffness and actomyosin contractility converge on cell spreading in an unexpected fashion to control a key aspect of cell fate.

Unsaturated polyester resin based composites: A case study of lignin valorisation.

Materials from green resources boast a low carbon footprint, forming the foundation of the circular economy approach in materials science. Thus, in this study, waste poly(ethylene terephthalate) (PET) was subjected to depolymerization using propylene glycol (PG), and subsequent polycondensation with bio-based maleic anhydride (MA) produced unsaturated polyester resin (b-UPR). Bio-derived acryloyl-modified Kraft lignin (KfL-A) served as a vinyl reactive filler in the b-UPR matrix to create b-UPR/KfL-A composites. The structural characterization of KfL-A and b-UPR involved the use of FTIR and NMR techniques. The mechanical properties of the newly fabricated composites were assessed through tensile strength, Vickers microhardness, and dynamic mechanical tests. The addition of KfL-A to the rigid b-UPR matrix enhanced material flexibility, resulting in less stiff and hard materials while preserving composite toughness. For instance, incorporating 10 wt% of KfL-A in b-UPR led to a 17% reduction in hardness, a 48% decrease in tensile strength, and a 20% reduction in toughness. Positive environmental impact was achieved by incorporation of 64 wt% of renewable and recycled raw material. Analogously prepared b-UPR/KfL composites showed structural inhomogeneity and somewhat better mechanical properties. Transmission (TEM) and scanning (SEM) electron microscopies revealed a suitable relationship between mechanical and structural properties of composites in relation to the extent of KfL-A addition. The UL94V flammability rating confirmed that flame resistance increased proportionally with the KfL-A addition. Once deposited in a landfill, these composites are expected to disintegrate more easily than PET, causing less harm to the environment and contributing to sustainability in the plastics cycle.

Vaccinium myrtillus L. Leaf Waste as a Source of Biologically Potent Compounds: Optimization of Polyphenol Extractions, Chemical Profile, and Biological Properties of the Extracts.

The aims of the present research include (1) optimization of extraction from Vaccinium myrtillus leaf waste via investigation of plant material:medium ratio, extraction medium, and extraction period, employing extractions at room and high temperatures, or using ultrasound and microwaves (M, HAE, UAE, and MAE, respectively), (2) physicochemical characterization, and (3) investigation of extract biological potential. The statistical analysis revealed that optimal levels of parameters for the greatest polyphenolic yield were a proportion of 1:30 g/mL, ethyl alcohol 50% (v/v) during 2 min of microwave irradiation. By LC-MS analysis, 29 phenolic components were detected; HAE showed the highest richness of almost all determined polyphenols, while chlorogenic acid and quercetin 3-O-glucuronide were dominant. All extracts showed a high inhibition of Staphylococcus aureus growth. The effect of different parameters on extracts' antioxidant capacity depended on the used tests. The extracts also showed a stimulative influence on keratinocyte viability and anti-inflammatory activity (proven in cell-based ELISA and erythrocyte stabilization assays). The extraction procedure significantly affected the extraction yield (MAE ≥ maceration ≥ UAE ≥ HAE), whereas conductivity, density, surface tension, and viscosity varied in a narrow range. The presented research provides evidence on the optimal extraction conditions and technique, chemical composition, and antioxidant, antimicrobial, anti-inflammatory, and keratinocyte viability properties of bilberry extracts for potential applications in pharmacy and cosmetics.

Phytochemical Analysis, Biological Activities, and Molecular Docking Studies of Root Extracts from Paeonia Species in Serbia.

Without being aware of their chemical composition, many cultures have used herbaceous peony roots for medicinal purposes. Modern phytopreparations intended for use in human therapy require specific knowledge about the chemistry of peony roots and their biological activities. In this study, ethanol-water extracts were prepared by maceration and microwave- and ultrasound-assisted extractions (MAE and UAE, respectively) in order to obtain bioactive molecules from the roots of Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L. wild growing in Serbia. Chemical characterization; polyphenol and flavonoid content; antioxidant, multianti-enzymatic, and antibacterial activities of extracts; and in vitro gastrointestinal digestion (GID) of hot water extracts were performed. The strongest anti-cholinesterase activity was observed in PT extracts. The highest anti-ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical potential was observed in PP extracts, whereas against DPPH (2,2-diphenyl-1-picrylhydrazyl radicals), the best results were achieved with PO extracts. Regarding antibacterial activity, extracts were strongly potent against Bacillus cereus. A molecular docking simulation was conducted to gather insights into the binding affinity and interactions of polyphenols and other Paeonia-specific molecules in the active sites of tested enzymes. In vitro GID of Paeonia teas showed a different recovery and behavior of the individual bioactives, with an increased recovery of methyl gallate and digallate and a decreased recovery of paeoniflorin and its derivatives. PT (Gulenovci) and PP (Pirot) extracts obtained by UAE and M were more efficient in the majority of the bioactivity assays. This study represents an initial step toward the possible application of Paeonia root extracts in pharmacy, medicine, and food technologies.

Matrices of physiologic stiffness potently inactivate idiopathic pulmonary fibrosis fibroblasts.

Fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) have been shown to differ from normal lung fibroblasts in functional behaviors that contribute to the pathogenesis of IPF, including the expression of contractile proteins and proliferation, but how such behaviors vary in matrices with stiffness matched to normal and fibrotic lung tissue remains unknown. Here, we tested whether pathologic changes in matrix stiffness control IPF and normal lung tissue-derived fibroblast functions, and compared the relative efficacy of mechanical cues to an antifibrotic lipid mediator, prostaglandin E(2) (PGE(2)). Fibroblasts were grown on collagen I-coated glass or hydrogel substrates of discrete stiffnesses, spanning the range of normal and fibrotic lung tissue. Traction microscopy was used to quantify contractile function. The CyQuant Cell Proliferation Assay (Invitrogen, Carlsbad, CA) was used to assess changes in cell number, and PGE(2) concentrations were measured by ELISA. We confirmed differences in proliferation and PGE(2) synthesis between IPF and normal tissue-derived fibroblasts on rigid substrates. However, IPF fibroblasts remained highly responsive to changes in matrix stiffness, and both proliferative and contractile differences between IPF and normal fibroblasts were ablated on physiologically soft matrices. We also confirmed the relative resistance of IPF fibroblasts to PGE(2), while demonstrating that decreases in matrix stiffness and the inhibition of Rho kinase both potently attenuate contractile function in IPF-derived fibroblasts. We conclude that pathologic changes in the mechanical environment control important IPF fibroblast functions. Understanding how mechanical cues control fibroblast function may offer new opportunities for targeting these cells, even when they are resistant to antifibrotic pharmacological agents or biological mediators.

Biomimetics Design of Tooth Root Zone at Cylindrical Gears Profile.

During the last few decades, the requirements for modern machine elements in terms of size reduction, increasing the energy efficiency, and a higher load capacity of standard and non-standard gears have been very prevalent issues. Within these demands, the main goals are the optimization of the gears' tooth profiles, as well as the investigation of new tooth profile designs. The presented design idea is based on the optimal solutions inspired by nature. Special attention is paid to the new design of the tooth root zones of spur gears in order to decrease the stress concentration values and increase the tooth root fatigue resistance. The finite element method is used for stress and strain state calculations, and the particular gear pair is modeled and optimized for these purposes. For tooth root strength analysis, the estimations are based on the theory of critical distances and the stress gradients obtained through finite element analysis. The obtained stress gradients have shown important improvements in the stress distribution in the transition zone optimized by biomimetics. An analysis of the material variation influence is also performed. Based on the investigations of a particular gear pair, a significant stress reduction of about 7% for steel gears and about 10.3% for cast iron gears is obtained for tooth roots optimized by bio-inspired design.

Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα.

Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery.

From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities.

In the study, the optimization of the extraction from Aloe vera leaf waste was performed via varying solid-to-solvent ratio, solvent type, extraction time, and technique (maceration, heat-, ultrasound-, and microwave-assisted extractions-HAE, UAE, and MAE, respectively). The optimal extraction conditions for achieving the highest polyphenol content are a 1:30 ratio, 70% ethanol, and 30 min of HAE. Total flavonoid and protein contents were significantly higher in the extract from MAE, while total condensed tannin content was the highest in HAE. LC-MS analysis quantified 13 anthraquinone and chromone compounds. The variations in the FT-IR spectra of the extracts obtained by different extraction procedures are minor. The influence of extraction conditions on the antioxidant ability of the extracts depended on applied antioxidant assays. The extracts possessed medium inhibition properties against Staphylococcus aureus and weak inhibitory activity against Enterococcus feacalis. The extracts had stimulative effect on HaCaT cell viability. Regarding the extraction yield, there was a significant difference between the used extraction techniques (MAE > HAE > maceration and UAE). The presented study is an initial step in the production of polyphenol-rich extracts from A. vera leaf waste aimed to be used for the potential preparation of pharmaceutical and cosmetic formulations for the skin.

Synthesis, Characterization and Application of Biobased Unsaturated Polyester Resin Reinforced with Unmodified/Modified Biosilica Nanoparticles.

This paper presents sustainable technology for environmentally friendly composite production. Biobased unsaturated polyester resin (b-UPR), synthesized from waste polyethylene terephthalate (PET) glycosylate and renewable origin maleic anhydride (MAnh) and propylene glycol (PG), was reinforced with unmodified and vinyl-modified biosilica nanoparticles obtained from rice husk. The structural and morphological properties of the obtained particles, b-UPR, as well as composites, were characterized by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The study of the influence of biosilica modification on the mechanical properties of composites was supported by hardness modeling. Improvement of the tensile strength of the b-UPR-based composite at 2.5 wt.% addition of biosilica modified with vinyl silane, named "b-UPR/SiO2-V" composite, has been achieved with 88% increase. The thermal aging process applied to the b-UPR/SiO2-V composite, which simulates use over the product's lifetime, leads to the deterioration of composites that were used as fillers in commercial unsaturated polyester resin (c-UPR). The grinded artificially aged b-UPR composites were used as filler in c-UPR for the production of a table top layer with outstanding mechanical properties, i.e., impact resistance and microhardness, as well as fire resistance rated in the V-0 category according to the UL-94 test. Developing sustainable composites that are chemically synthesized from renewable sources is important from the aspect of preserving the environment and existing resources as well as the extending their life cycle.

Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-ß responsiveness.

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-ß1 (TGF-ß1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-ß1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-ß1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation.

Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings.

In this work, nanocomposite fibres and microfibres based on alginate and poly(vinyl alcohol) (PVA) with silver nanoparticles (AgNPs) were produced and characterized for potential application as antibacterial wound dressings. PVA/Ag/Na-alginate colloid solution was used for the preparation of the fibres by a simple extrusion technique followed by freezing-thawing cycles. UV-Visible spectroscopy confirmed successful preservation of AgNPs in fibres while Fourier transform infrared spectroscopy has shown a balanced combined effect on the Ca-alginate spatial arrangement with the addition of both AgNPs and PVA. The presence of PVA in fibres induced an increase in the swelling degree as compared with that of Ag/Ca-alginate fibres (approx. 28 versus approx. 14). Still, the initially produced PVA/Ca-alginate fibres were mechanically weaker than Ca-alginate fibres, but after drying and rehydration exhibited better mechanical properties. Also, the obtained fibres released AgNPs and/or silver ions at the concentration of approximately 2.6 µg cm-3 leading to bacteriostatic effects against Staphylococcus aureus and Escherichia coli. These results are relevant for practical utilization of the fibres, which could be stored and applied in the dry form with preserved mechanical stability, sorption capacity and antibacterial activity.

Determination of Mechanical Properties of Epoxy Composite Materials Reinforced with Silicate Nanofillers Using Digital Image Correlation (DIC).

In this study, silicate nanofillers; dicalcium silicate, magnesium silicate, tricalcium silicate, and wollastonite; were synthesized using four different methods and incorporated into the epoxy resin to improve its mechanical properties. Characterization of the newly synthesized nanofillers was performed using Fourier-transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The purpose of this study was to analyze newly developed composite materials reinforced with silicate nanoparticles utilizing tensile testing and a full-field non-contact 3D Digital Image Correlation (DIC) method. Analysis of deformation and displacement fields gives precise material behavior during testing. Testing results allowed a more reliable assessment of the structural integrity of epoxy composite materials reinforced using different silicate nanofillers. It was concluded that the addition of 3% of dicalcium silicate, magnesium silicate, tricalcium silicate, and wollastonite lead to the increasement of tensile strength up to 31.5%, 29.0%, 27.5%, and 23.5% in comparison with neat epoxy, respectively. In order to offer more trustworthy information about the viscoelastic behavior of neat epoxy and composites, a dynamic mechanical analysis (DMA) was also performed and rheological measurements of uncured epoxy matrix and epoxy suspensions were obtained.