Search Results (27)

Background: PP-007 (SANGUINATE^®, PEGylated carboxyhemoglobin, bovine) is under development to treat conditions of ischemia/hypoxia. Hemorrhagic/hypovolemic shock (H/HVS) becomes a life-threatening comorbidity due in part to hypotension and hypoxia. Blood transfusions are indicated, but supply and compatibility issues may limit subject access or when blood is not an option due to religious restriction or concern for clinical complications. PP-007 is universally compatible with an effective hydrodynamic radius and colloidal osmotic pressure facilitating perfusion without promoting extravasation. Methods: A review of previous clinical trials was performed and revealed an Open-Label Phase 1 safety study of acute severe anemia (hemoglobin ≤ 5 g/dL) in adult (≥18 y) patients unable to receive red blood cell transfusion (NCT02754999). Primary outcomes included safety events with secondary efficacy measures of organ function and survival at 1, 14, and 28 days. Additionally, a retrospective review of published, peer-reviewed case reports was performed, evaluating the administration of Sanguinate for Expanded Access in those patient populations where blood was not an option over the past 12 years. Results: A total of 103 subjects were enrolled in the Phase I safety study with significant co-morbidities that most commonly included hypertension (n = 43), acute and chronic kidney disease (n = 38), diabetes mellitus (n = 29), gastrointestinal bleeds (n = 18), and sickle cell disease (n = 13). Enrollment characteristics included decreased hemoglobin and severe anemia (mean baseline hemoglobin of 4.2 g/dL). Treatments included an average of three infusions [range 1–17]. Secondary efficacy measures were mean Hb levels, respiratory support, and vasopressor requirements, all demonstrating clinically relevant improvements. Fourteen additional cases were identified in the literature. Though one patient died due to pre-treatment conditions, all patients but one were discharged home in stable condition. Conclusion: Collectively, these observations are encouraging and provide support for the continued evaluation of PP-007 in advanced clinical trials in severe anemia including H/HVS. The review of published case reports underscored the potential of Sanguinate to reduce early mortality. Adverse effects included transient hypertension, lethargy, dizziness, and troponin elevation. These findings highlight the need for continued research and funding of blood alternatives to improve outcomes when standard blood transfusions are unavailable or contraindicated. Full article

This study elucidated the mechanistic interplay between the extrusion parameters (temperature and screw speed), starch molecular architecture (chain-length distribution), and key physicochemical properties of wheat flour extrudates. Four wheat flours with varied amylose contents were extruded, where the average hydrodynamic radius ($\stackrel{\mathrm{-}}{R_h}$) was reduced by 75.5% in normal wheat (e.g., CM55), while waxy wheat (WW) exhibited higher $\stackrel{\mathrm{-}}{R_h}$. Crispness correlated negatively with long amylopectin branches (36 < X ≤ 100), with WW displaying superior crispness (12.22 N/mm). Short amylopectin chains (X 6–36) increased under thermomechanical stress, enhancing the expansion index (SEI), whereas long chains (X > 100) restricted expansion. Temperature may modulate color difference (ΔE) via Maillard reactions, while higher specific mechanical energy (SME) intensified browning. Higher temperatures (>170 °C), rather than SME, caused significant changes in the proportion of short branches and long branches, with SME exhibiting a negative correlation with $\stackrel{\mathrm{-}}{R_h}$, indicative of substantial molecular degradation. The starch chain-length distribution, rather than amylose content alone, dictates extrudate functionality. Full article

The present study reported, for the first time, the fabrication and characterization of electrospun nanofibers based on arabinoxylans (AXs) alone. The Fourier transform infrared spectrum of ferulated water-extractable AXs recovered from wheat endosperm confirmed the molecule identity. The carbon and oxygen signals in X-ray photoelectron spectrometry (XPS) were recorded for this molecule. The AXs had weight-average molar mass, intrinsic viscosity, radius of gyration, and hydrodynamic radius values of 769 kDa, 4.51 dL/g, 55 nm, and 31 nm, respectively. The calculated AX characteristic ratio and persistence length were 10.7 and 3.2 nm, respectively, while the Mark–Houwink–Sakurada α and K constants were 0.31 and 9.4, respectively. These macromolecular characteristics indicate a molecular random coil structure in the polysaccharide. Using aqueous acetic acid 50% (v/v) as a solvent favored the Taylor cone establishment and the fabrication of electrospun nanofibers. The morphology of nanofibers was revealed by scanning electron microscopy images. Atomic force microscopy analysis of AX nanofibers exposed the material deposition in layers; these nanofibers had an average diameter of 177 nm. These nanofibers could be used as advanced biomaterials for biomedical applications such as wound dressing. Full article

This study investigated the influence of parameters such as pH condition, polyelectrolyte concentration, polymer ratio, and order of addition of the commercial polyelectrolytes chitosan and iota-carrageenan (ι-carrageenan) on the formation of polymeric nanoparticles in suspension (coacervates). A preliminary purification step of the polymers was essential for obtaining stable nanoparticles with small sizes as impurities, particularly metal ions that interfere with complexation, are removed by dialysis. Microparticles (13.5 μm in dry diameter) are obtained when aliquots of chitosan solution are poured into the ι-carrageenan solution. In general, an excess of chitosan results in the formation of agglomerated particles. The addition of an aliquot of ι-carrageenan solution (30 mL at 0.6 mg/mL and pH 4.0) to the chitosan solution (6.0 mL at 0.3 mg/mL and pH 4.0) leads to dispersed nanoparticles with a hydrodynamic radius of 278 ± 5 nm, a zeta potential of −31 ± 3 mV, and an average dry diameter of 45 ± 11 nm. The hydrodynamic radius increases as the pH rises. The partial deprotonation of ι-carrageenan chains enhances the interaction with water molecules, causing the particles to swell. These findings contribute to the fundamental understanding of polyelectrolyte complexation processes in aqueous suspension and provide insights for developing stable nanomaterials for potential practical applications. Full article

Hydraulic fracturing of deep, high-temperature reservoirs poses challenges due to elevated temperatures and high fracture pressures. Conventional polymer fracturing fluid (QCL) has high viscosity upon adding cross-linking agents and significantly increases wellbore friction. This paper examines a polymer fracturing fluid with pH response and low friction. Experimental results indicate that cross-linking occurs quickly in acid, while alkali can slow the cross-linking process and reduce friction. Sodium carbonate (Na₂CO₃) serves as an effective candidate. An optimized formulation consisting of “salt + pH + polymer + cross-linking agent” is proposed in two stages: low viscosity for fracture generation and high viscosity for sand transport. PH control enhances polymer hydration, increasing sand-carrying in the low-viscosity stage. Scanning electron microscopy (SEM) reveals that the fluid’s structure varies with pH, showing that alkali promotes a stable network structure. Infrared spectroscopy (IR) shows that higher pH increases negative charges of the polymer chains, which enhances their hydrodynamic radius, slightly raises viscosity, and enhances sand carrying. Field tests confirm the formulation’s effectiveness, leading to lower operating pressures, stable sand transport, and notable production, averaging 107.57 m³ of oil and 276 m³ of gas per day. Overall, this research provides low-friction solutions for the efficient development of deep reservoirs. Full article

Rare-earth-doped nanoscaled BaGdF₅ is known as an efficient contrasting agent for X-ray micro-CT and NMR as well as a promising candidate for X-ray photodynamic therapy, thereby opening an opportunity for theragnostic applications. Conventional synthesis of Ln-doped BaGdF₅ consider a long-lasting batch procedure, while a conjugation with photosensitizer usually implies a separate stage requiring active mixing. To the best of our knowledge, in this work, we for the first time obtain BaGdF₅:Tb³⁺ nanophosphors in a microfluidic route at temperatures as low as 100 °C while decreasing the time of thermal treatment down to 6 min. The proposed synthesis route allows for the obtaining of single-phase and monodisperse BaGd_1−xF5:Tb_x³⁺ nanoparticles with an averaged particle size of ca. 7–9 nm and hydrodynamic radius around 22 nm, as estimated from TEM and DLS, respectively. In addition, X-ray-excited optical luminescence has been recorded in situ for the series of nanophosphors synthesis with varied flow rates of Tb³⁺ and Gd³⁺ stock solutions, thereby anticipating a possible application of microfluidics for screening a wide range of possible co-dopants and reaction conditions and its effect on the optical properties of the synthesized materials. Moreover, we demonstrated that BaGd_1−xF₅:Tb_x³⁺@RoseBengal conjugates might be obtained in a single-stage route by implementing an additional mixer at the synthesis outcome, namely, by mixing the resulting reaction mixture containing nanoparticles with an equivalent flow of photosensitizer aqueous solution. In vitro cytotoxicity test declares moderate toxicity effect on different cell lines, while the results of flow cytometry indirectly confirm cellular uptake. Finally, we report long-term biodistribution monitoring of the synthesized nanocomposites assessed by X-ray micro-CT in the in vivo experiments on balb/c mice, which depicts an unusual character of agents’ accumulation. Full article

Lindane (a harmful contaminant) was produced in Sabiñánigo (Huesca, Spain) and deposited at the Sardas landfill. This site contains a large mass of pollutants, which have an extremely large contamination potential of the Ebre River. The site has undergone numerous human interventions that have modified the natural conditions. The site exhibits complex hydrogeological patterns and has been monitored systematically for a long period of time, and a large amount of geological, hydrological, and hydrogeological data are available. Here, a 2D finite element groundwater flow model along a vertical profile heading east–west along the thalweg of the former gully is presented. The main goal is modelling groundwater flow through the landfill, the Gállego River alluvial aquifer, and its interactions with the Sabiñánigo reservoir. The numerical model confirms the prevailing conceptual hydrogeological model of the site. The main results include: (1) Groundwater flows into the landfill mainly along perimeter ditches, which do not properly drain the surface and subsurface runoff (13.84 m³/d) and from the underlying marly rock (8.84 m³/d); (2) The total landfill leachate outflow towards the alluvial floodplain underneath the front slurry wall through a shallow marl layer is equal to 17 m³/d; (3) The oscillations of the Sabiñánigo reservoir water level produce a tidal effect that results in periodic changes of the hydraulic gradient between the alluvial gravels and the reservoir; (4) Groundwater flows generally from the alluvial aquifer towards the reservoir in an average E–W direction with an average Darcy velocity equal to 5 cm/d. The flow direction, however, changes to W–E when the reservoir level rises suddenly and; (5) The hydrodynamic parameters of the alluvial silts and reservoir silting sediments are crucial in determining the influence radius of the inversion of groundwater flow direction when the reservoir level rises suddenly. Model results enhance the confidence of the conceptual model, provide the basis for detailed specific models of the landfill and the alluvial aquifer, and highlight the importance of considering the tidal effect of the reservoir level oscillations. They also provide valuable information for managing the landfill and its impact on the surrounding groundwater system. Full article

Curved channels are one of the most fundamental units of natural or artificial channels, in which there are different kinds of obstacles; these include vegetation patches, bridge piles, electrical tower foundations, etc., which are all present over a channel bend, and can significantly alter the hydrodynamic characteristics of a channel when compared to a bare bed. In this study, laboratory experiments and numerical simulations were combined to investigate the effect of a circular cylinder on the flow characteristics of a 180-degree U-shaped curved channel. Experimental data, including on water depth and three-dimensional velocity, which was obtained by utilizing acoustic Doppler velocimetry (ADV), were used to calibrate and verify the simulation results of the Reynolds-Averaged Navier–Stokes (RANS) model in the FLOW-3D software. Numerical results show that a larger cylinder diameter leads to an overall greater depth-averaged velocity at the section, a greater shear stress acting on the banks on which the cylinder is placed, and a greater increase in the depth-averaged velocity along the concave bank compared to that along the convex bank. When the diameter of the cylinder placed at the 90° section increases, two weaker circulations with the same direction are found near the water surface; for the submerged one, the two weaker circulations appear at the further downstream section, unlike the emergent one. The degree of variation degree in the shear stress acting on the banks is larger than that of the flowrate. As the flowrate increases or the radius of curvature decreases, the secondary flow intensity correspondingly elevates. However, the curvature radius of the curved channel plays a more important role in the secondary flow intensity than the flowrate does. For both the emergent and submergent cylinders, the large cylinder produces a greater secondary flow strength, but the emergent one has a greater secondary flow strength than the submergent one. In summary, the present study provides valuable knowledge on the hydrodynamics of flow around emergent and submergent structures over a curved channel, which could improve the future design of these structures. Full article

This article presents the results of the synthesis of Se NPs stabilized by a quaternary ammonium compound—catamine AB. Se NPs were obtained by chemical reduction in an aqueous medium. In the first stage of this study, the method of synthesis of Se NPs was optimized by a multifactorial experiment. The radius of the obtained samples was studied by dynamic light scattering, and the electrokinetic potential was studied using acoustic and electroacoustic spectrometry. Subsequently, the samples were studied by transmission electron microscopy, and the analysis of the data showed that a bimodal distribution is observed in negatively charged particles, where one fraction is represented by spheres with a diameter of 45 nm, and the second by 1 to 10 nm. In turn, positive Se NPs have a diameter of about 70 nm. In the next stage, the influence of the active acidity of the medium on the stability of Se NPs was studied. An analysis of the obtained data showed that both sols of Se NPs exhibit aggregative stability in the pH range from 2 to 6, while an increase in pH to an alkaline medium is accompanied by a loss of particle stability. Next, we studied the effect of ionic strength on the aggregative stability of Se NPs sols. It was found that negatively charged ions have a significant effect on the particle size of the positive sol of Se NPs, while the particle size of the negative sol is affected by positively charged ions. Full article

The aim of the study was to characterize raw aqueous extracts from Plantago ovata husk in terms of molecular chain mass, osmotic, hydrodynamic, and rheological properties. The raw extracts used in this study have not been yet investigated in the indicated research area. Determination of the molecular weight of the chains present in the extract was performed by gel permeation chromatography (GPC). Osmotic properties were characterized using membrane osmometry. Rheological properties were investigated via classical rotational rheology with normal force measurements, as well as less common but equally important measurements of extensional viscosity. Two types of chains with an average molecular mass of 200 and 1780 kDa were found. The values of the first virial coefficient (B₂) indicate the predominance of biopolymer-biopolymer interactions. The hydrodynamic radius established at 25 and 30 °C was 74 and 67 nm, respectively, and lower than at 40 °C (>600 nm). The first critical concentration was determined: $c^{*}=0.11 \mathrm{g}·{\mathrm{dL}}^{-1}$. The dominance of negative normal force values resulting from the formation of a pseudo-gel structure of the heteroxylates was demonstrated. Extensional viscosity measurement results revealed that the studied extracts cannot be treated as simple shear-thinning fluids, as indicated by shear flow, but should be considered as viscoelastic fluids. Full article

Renewable natural and synthetic basic substances can be used to produce biodegradable polymers. Several methods of the polymerization of terpene limonene have been evaluated. The polymerization methods evaluated are radical polymerization, cationic polymerization and thiol-ene polymerization. The free-radical polymerization of limonene with azobisisobutyronitrile (AIBN) as an initiator was carried out. The cationic polymerization of limonene was carried out using AlCl₃ as a catalyst. The copolymerization of limonene with mercaptoethanol, 2-mercaptoethyl ether without an initiator and with an AIBN initiator was studied and it was also shown that polymerization can proceed spontaneously. The resulting compounds were investigated by NMR and FTIR spectroscopy. The values of the molecular weight characteristics of the samples obtained are presented, such as: number-average molecular weight, hydrodynamic radius and characteristic viscosity, depending on the method of production. The coefficients α (molecular shape) in the Mark–Kuhn–Houwink equation are determined according to the established values of the characteristic viscosity. According to the values obtained, the AC molecules in solution have parameters α 0.14 to 0.26, which corresponds to a good solvent and the molecular shape-dense coil. Full article

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) perform diverse functions in cellular organization, transport and signaling. Unlike the well-defined structures of the classical natively folded proteins, IDPs and IDRs dynamically span large conformational and structural ensembles. This dynamic disorder impedes the study of the relationship between the amino acid sequences of the IDPs and their spatial structures and dynamics, with different experimental techniques often offering seemingly contradictory results. Although experimental and theoretical evidence indicates that some IDP properties can be understood based on their average biophysical properties and amino acid composition, other aspects of IDP function are dictated by the specifics of the amino acid sequence. We investigate the effects of several key variables on the dimensions and the dynamics of IDPs using coarse-grained polymer models. We focus on the sequence “patchiness” informed by the sequence and biophysical properties of different classes of IDPs—and in particular FG nucleoporins of the nuclear pore complex (NPC). We show that the sequence composition and patterning are well reflected in the global conformational variables such as the radius of gyration and hydrodynamic radius, while the end-to-end distance and dynamics are highly sequence-specific. We find that in good solvent conditions highly heterogeneous sequences of IDPs can be well mapped onto averaged minimal polymer models for the purpose of prediction of the IDPs dimensions and dynamic relaxation times. The coarse-grained simulations are in a good agreement with the results of atomistic MD. We discuss the implications of these results for the interpretation of the recent experimental measurements, and for the further applications of mesoscopic models of FG nucleoporins and IDPs more broadly. Full article

For the first time, double stimuli-responsive properties of poly(N-isopropylacrylamide) (PNIPA) and poly(1-vinylimidazole) (PVIM) block copolymers in aqueous solutions were studied. The synthesis of PNIPA₆₀-b-PVIM₉₀ and PNIPA₂₈-b-PVIM₆₂-b-PNIPA₂₉ was performed using reversible addition–fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by size exclusion chromatography and ¹H NMR spectroscopy. The conformational behavior of the polymers was studied using dynamic light scattering (DLS) and fluorescence spectroscopy (FS). It was found that PNIPA and block copolymers conformation and ability for self-assembly in aqueous medium below and above cloud point temperature depend on the locus of hydrophobic groups derived from the RAFT agent within the chain. Additionally, the length of PVIM block, its locus in the chain and charge perform an important role in the stabilization of macromolecular micelles and aggregates below and above cloud point temperature. At 25 °C the average hydrodynamic radius (R_h) of the block copolymer particles at pH 3 is lower than at pH 9 implying the self-assembling of macromolecules in the latter case. Cloud points of PNIPA₆₀-b-PVIM₉₀ are ~43 °C and ~37 °C at a pH of 3 and 9 and of PNIPA₂₈-b-PVIM₆₂-b-PNIPA₂₉ they are ~35 °C and 31 °C at a pH of 3 and 9. Around cloud point independently of pH, the R_h value for triblock copolymer rises sharply, achieves the maximum value, then falls and reaches the constant value, while for diblock copolymer, it steadily grows after reaching cloud point. The information about polarity of microenvironment around polymer obtained by FS accords with DLS data. Full article

A facile technique for the preparation of mixed polylactide micelles from amorphous poly-D,L-lactide-block-polyethyleneglycol and crystalline amino-terminated poly-L-lactide is described. In comparison to the classical routine solvent substitution method, the ultrasonication assisted formation of polymer micelles allows shortening of the preparation time from several days to 15–20 min. The structure and morphology of mixed micelles were analyzed with the assistance of electron microscopy, dynamic and static light scattering and differential scanning calorimetery. The resulting polymer micelles have a hydrodynamic radius of about 150 nm and a narrow size distribution. The average molecular weight of micelles was found to be 2.1 × 10⁷ and the aggregation number was calculated to be 6000. The obtained biocompatible particles were shown to possess low cytotoxicity, high colloid stability and high stability towards enzymatic hydrolysis. The possible application of mixed polylactide micelles as drug delivery vehicles was studied for the antitumor hydrophobic drug paclitaxel. The lethal concentration (LC50) of paclitaxel encapsulated in polylactide micelles was found to be 42 ± 4 µg/mL—a value equal to the LC50 of paclitaxel in the commercial drug Paclitaxel-Teva. Full article

A new series of tin(II) complexes (1, 2, 4, and 5) were successfully synthesized by employing hydroxy functionalized pyridine ligands, specifically 2-hydroxypyridine (hpH), 8-hydroxyquinoline (hqH), and 10-hydroxybenzo[h]quinoline (hbqH) as stabilizing ligands. Complexes [Sn(μ-κ²ON-OC₅H₄N)(N{SiMe₃}₂)]₂ (1) and [Sn₄(μ-κ²ON-OC₅H₄N)₆(κ¹O-OC₅H₄N)₂] (2) are the first structurally characterized examples of tin(II) oxypyridinato complexes exhibiting {Sn₂(OCN)₂} heterocyclic cores. As part of our study, ¹H DOSY NMR experiments were undertaken using an external calibration curve (ECC) approach, with temperature-independent normalized diffusion coefficients, to determine the nature of oligomerisation of 2 in solution. An experimentally determined diffusion coefficient (298 K) of 6.87 × 10⁻¹⁰ m² s⁻¹ corresponds to a hydrodynamic radius of Ca. 4.95 Å. This is consistent with the observation of an averaged hydrodynamic radii and equilibria between dimeric [Sn{hp}₂]₂ and tetrameric [Sn{hp}₂]₄ species at 298 K. Testing this hypothesis, ¹H DOSY NMR experiments were undertaken at regular intervals between 298 K–348 K and show a clear change in the calculated hydrodynamic radii form 4.95 Å (298 K) to 4.35 Å (348 K) consistent with a tetramer ⇄ dimer equilibria which lies towards the dimeric species at higher temperatures. Using these data, thermodynamic parameters for the equilibrium (ΔH° = 70.4 (±9.22) kJ mol⁻¹, ΔS° = 259 (±29.5) J K⁻¹ mol⁻¹ and ΔG°₂₉₈ = −6.97 (±12.7) kJ mol⁻¹) were calculated. In the course of our studies, the Sn(II) oxo cluster, [Sn₆(m³-O)₆(OR)₄:{Sn^(II)(OR)₂}₂] (3) (R = C₅H₄N) was serendipitously isolated, and its molecular structure was determined by single-crystal X-ray diffraction analysis. However, attempts to characterise the complex by multinuclear NMR spectroscopy were thwarted by solubility issues, and attempts to synthesise 3 on a larger scale were unsuccessful. In contrast to the oligomeric structures observed for 1 and 2, single-crystal X-ray diffraction studies unambiguously establish the monomeric 4-coordinate solid-state structures of [Sn(κ²ON-OC₉H₆N)₂)] (4) and [Sn(κ²ON-OC₁₃H₈N)₂)] (5). Full article