Dual-Functional Implant Based on Gellan-Xanthan Hydrogel with Diopside, BMP-2 and Lysostaphin for Bone Defect Repair and Control of Staphylococcal Infection.

A new dual-functional implant based on gellan-xanthan hydrogel with calcium-magnesium silicate ceramic diopside and recombinant lysostaphin and bone morphogenetic protein 2 (BMP-2)-ray is developed. In this composite, BMP-2 is immobilized on microparticles of diopside while lysostaphin is mixed directly into the hydrogel, providing sustained release of BMP-2 to allow gradual bone formation and rapid release of lysostaphin to eliminate infection immediately after implantation. Introduction of diopside of up to 3% (w/v) has a negligible effect on the mechanical properties of the hydrogel but provides a high sorption capacity for BMP-2. The hydrogels show good biocompatibility and antibacterial activity. Lysostaphin released from the implants over a 3 h period efficiently kills planktonic cells and completely destroys 24 h pre-formed biofilms of Staphylococcus aureus. Furthermore, in vivo experiments in a mouse model of critically-sized cranial defects infected with S. aureus show a complete lack of osteogenesis when implants contain only BMP-2, whereas, in the presence of lysostaphin, complete closure of the defect with newly formed mineralized bone tissue is observed. Thus, the new implantable gellan-xanthan hydrogel with diopside and recombinant lysostaphin and BMP-2 shows both osteogenic and antibacterial properties and represents a promising material for the treatment and/or prevention of osteomyelitis after bone trauma.

Monitoring of meat quality and change-point detection by a sensor array and profiling of bacterial communities.

BACKGROUND: Real-time monitoring of food consumer quality remains challenging due to diverse bio-chemical processes taking place in the food matrices, and hence it requires accurate analytical methods. Thresholds to determine spoiled food are often difficult to set. The existing analytical methods are too complicated for rapid in situ screening of foodstuff. RESULTS: We have studied the dynamics of meat spoilage by electronic nose (e-nose) for digitizing the smell associated with volatile spoilage markers of meat, comparing the results with changes in the microbiome composition of the spoiling meat samples. We apply the time series analysis to follow dynamic changes in the gas profile extracted from the e-nose responses and to identify the change-point window of the meat state. The obtained e-nose features correlate with changes in the microbiome composition such as increase in the proportion of Brochothrix and Pseudomonas spp. and disappearance of Mycoplasma spp., and with representative gas sensors towards hydrogen, ammonia, and alcohol vapors with R2 values of 0.98, 0.93, and 0.91, respectively. Integration of e-nose and computer vision into a single analytical panel improved the meat state identification accuracy up to 0.85, allowing for more reliable meat state assessment. SIGNIFICANCE: Accurate identification of the change-point in the meat state achieved by digitalizing volatile spoilage markers from the e-nose unit holds promises for application of smart miniaturized devices in food industry.

Sequential Modification of Pyrrole Ring with up to Three Different Nucleophiles.

An umpolung strategy was used for the preparation of highly functionalized 3-pyrrolin-2-ones. This approach involves dearomative double chlorination of 1H-pyrroles to form highly reactive dichloro-substituted 2H-pyrroles. The resulting intermediate reacts selectively with wet alcohols to form the corresponding alkoxy-substituted 3-pyrrolin-2-ones via double nucleophilic substitution in up to 99% yield. The subsequent reaction with different N-, O-, and S-nucleophiles opens access to highly functionalized pyrrolinones bearing additional functionality. The overall outcome of the reported sequence is step-by-step nucleophilic modification of pyrroles with three different nucleophiles. All steps were found to be highly efficient and 100% regioselective. This transformation proceeds under mild conditions and does not require any catalyst to give final products in very high yields. The obtained experimental results are in perfect agreement with the data obtained by theoretical investigation of these reactions.

Orientational and crystallographic relationships in thin films of yttrium orthoferrite on sapphire substrates.

An algorithm is proposed for determining the orientational relationships and crystal unit-cell parameters of thin films using a laboratory X-ray diffractometer and stereographic projections. It is illustrated by the treatment of experimental data obtained for yttrium orthoferrite YFeO3 films on single crystalline sapphire (Al2O3) substrates for film thicknesses in the range from 100 to 7000 Å. Precise determination of unit-cell constants and angles is possible by combining the results of X-ray measurements made in the in-plane and out-of-plane geometries. The unit-cell unit parameters and orientation relationships for thin films were determined. For the studied films, typical errors in determining unit-cell parameters and angles are better than 0.17 Šand 0.17°, respectively.

The diamond-silicon carbide composite Skeleton® as a promising material for substrates of intense X-ray beam optics.

The paper considers the possibility of using the diamond-silicon carbide composite Skeleton® with a technological coating of polycrystalline silicon as a substrate for X-ray mirrors used with powerful synchrotron radiation sources (third+ and fourth generation). Samples were studied after polishing to provide the following surface parameters: root-mean-square flatness ≃ 50 nm, micro-roughness on the frame 2 µm × 2 µm σ ≃ 0.15 nm. The heat capacity, thermal conductivity and coefficient of linear thermal expansion were investigated. For comparison, a monocrystalline silicon sample was studied under the same conditions using the same methods. The value of the coefficient of linear thermal expansion turned out to be higher than that of monocrystalline silicon and amounted to 4.3 × 10-6 K-1, and the values of thermal conductivity (5.0 W cm-1 K-1) and heat capacity (1.2 J K-1 g-1) also exceeded the values for Si. Thermally induced deformations of both Skeleton® and monocrystalline silicon samples under irradiation with a CO2 laser beam have also been experimentally studied. Taking into account the obtained thermophysical constants, the calculation of thermally induced deformation under irradiation with hard (20 keV) X-rays showed almost three times less deformation of the Skeleton® sample than of the monocrystalline silicon sample.

Pinning Forces on the Omniphobic Dry, Liquid-Infused, and Liquid-Attached Surfaces.

Omniphobic coatings effectively repelling water, oils, and other liquids are of great interest and have a broad number of applications including self-cleaning, anti-icing surfaces, biofouling protection, selective filtration, etc. To create such coatings, one should minimize the pinning force that resists droplet motion and causes contact angle hysteresis. The minimization of the free surface energy by means of the chemical modification of the solid surface is not enough to obtain a nonsticky slippery omniphobic surface. One should minimize the contact between the solid and the droplet. Besides coating the surface with flat polymer films, among the major approaches to create omniphobic coatings, one can reveal "lotus effect" textured coatings, slippery liquid-infused porous surfaces (SLIPS), and slippery omniphobic covalently attached liquid (SOCAL) coatings. It is possible to turn one surface type into other by texturizing, impregnating with liquids, or grafting flexible liquid-like polymer chains. There are a number of models describing the pinning force on surfaces, but the transitions between states with different wetting regimes remain poorly understood. At the same time, such studies can significantly broaden existing ideas about the physics of wetting, help to design coatings, and also contribute to the development of generalized models of the pinning force. Here we review the existing pinning force (contact angle hysteresis) models on various omniphobic substrates. Also, we discuss the current studies of the pinning force in the transitions between different wetting regimes.

Fluorescence lifetime multiplexing with fluorogen activating protein FAST variants.

In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Complete photonic bandgap in a low-index two-dimensional quasicrystalline structure.

A bandgap in the continuum spectrum of photons in addition to its basic physical significance has strong potential for applications. Analogous to semiconductor crystals for electrons, periodic dielectric structures named photonic crystals were proposed to control photon flux propagation. In our search for low refractive index (RI) structures with a photonic bandgap, initial research efforts were focused on photonic crystal design, while aperiodic structures allow lower values of refractive index contrast to sustain a photonic bandgap. Here, we report on a two-dimensional quasicrystalline structure designed as a set of one-dimensional lattices merged into a single binary structure made of two materials with refractive index contrast 2|n1 - n2|/(n1 + n2) = 0.16 and even less in theory. We confirmed the theoretical prediction of bandgap exciting by measuring the radiation suppression of a dipole source placed in the center of the quasicrystalline structure. The full-wave numerical simulations and the experimental study appear to be in good agreement with the theoretical model.

Advanced applications of Nanodiscs-based platforms for antibodies discovery.

Due to their fundamental biological importance, membrane proteins (MPs) are attractive targets for drug discovery, with cell surface receptors, transporters, ion channels, and membrane-bound enzymes being of particular interest. However, due to numerous challenges, these proteins present underutilized opportunities for discovering biotherapeutics. Antibodies hold the promise of exquisite specificity and adaptability, making them the ideal candidates for targeting complex membrane proteins. They can target specific conformations of a particular membrane protein and can be engineered into various formats. Generating specific and effective antibodies targeting these proteins is no easy task due to several factors. The antigen's design, antibody-generation strategies, lead optimization technologies, and antibody modalities can be modified to tackle these challenges. The rational employment of cutting-edge lipid nanoparticle systems for retrieving the membrane antigen has been successfully implemented to simplify the mechanism-based therapeutic antibody discovery approach. Despite the highlighted MP production challenges, this review unequivocally underscores the advantages of targeting complex membrane proteins with antibodies and designing membrane protein antigens. Selected examples of lipid nanoparticle success have been illustrated, emphasizing the potential of therapeutic antibody discovery in this regard. With further research and development, we can overcome these challenges and unlock the full potential of therapeutic antibodies directed to target complex MPs.

Optimal Dynamic Regimes for CO Oxidation Discovered by Reinforcement Learning.

Metal nanoparticles are widely used as heterogeneous catalysts to activate adsorbed molecules and reduce the energy barrier of the reaction. Reaction product yield depends on the interplay between elementary processes: adsorption, activation, desorption, and reaction. These processes, in turn, depend on the inlet gas composition, temperature, and pressure. At a steady state, the active surface sites may be inaccessible due to adsorbed reagents. Periodic regime may thus improve the yield, but the appropriate period and waveform are not known in advance. Dynamic control should account for surface and atmospheric modifications and adjust reaction parameters according to the current state of the system and its history. In this work, we applied a reinforcement learning algorithm to control CO oxidation on a palladium catalyst. The policy gradient algorithm was trained in the theoretical environment, parametrized from experimental data. The algorithm learned to maximize the CO2 formation rate based on CO and O2 partial pressures for several successive time steps. Within a unified approach, we found optimal stationary, periodic, and nonperiodic regimes for different problem formulations and gained insight into why the dynamic regime can be preferential. In general, this work contributes to the task of popularizing the reinforcement learning approach in the field of catalytic science.

Crystal structure and Hirshfeld surface analysis of 1-[6-bromo-2-(4-fluoro-phen-yl)-1,2,3,4-tetra-hydroquinolin-4-yl]pyrrolidin-2-one.

In the title compound, C19H18BrFN2O, the pyrrolidine ring adopts an envelope conformation. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O, C-H⋯O, C-H⋯F and C-H⋯Br hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions connect mol-ecules into ribbons along the b-axis direction, consolidating the mol-ecular packing. The inter-molecular inter-actions in the crystal structure were qu-anti-fied and analysed using Hirshfeld surface analysis.

Synthesis of Technetium Carboxylates: Wheel-Like Octanuclear Clusters (Tc8(µ-O)8(RCOO)16, Where R = CF3, C6H5)─Potential Nanobuilding Units for Tc-MOFs.

Herein, we studied the behavior of TcO4- in trifluoroacetic anhydride (TFAA) under visible light irradiation in situ by UV-vis spectroscopy. One carboxylate of Tc(VII) C2F3O5Tc (1) and two wheel-like carboxylate clusters of Tc(IV) Tc8(µ-O)8(CF3COO)16 (2, 3) and Tc8(µ-O)8(C6H5COO)16 (4) were synthesized and analyzed using pXRD, TGA, UV-vis spectroscopy, and SCXRD techniques. According to SCXRD, it was found that Tc(IV) trifluoroacetate exists in two crystalline modifications. By UV-vis spectroscopy and DFT calculations, it was shown that the primary compound in the reaction system is trifluoroacetate Tc(VII). A technetium trifluoroacetate(VII) and Tc intermediates of unidentified nature both show photosensitivity. The influence of intermolecular noncovalent interactions on the volatility of trifluoroacetate and benzoate Tc(IV) is shown. The main regularities of chemical transformations of technetium in nonaqueous solutions of carboxylates have been revealed. The obtained data on the kinetics of the process suggest that technetium in trifluoroacetic anhydride can simultaneously exist in the form of Tc(VII), Tc(VI), Tc(V), and Tc(IV). Under laser ionization or prolonged heating, the formation of the Tc(II,III)-cluster is observed.

Continuous-flow separation and preconcentration of microplastics from natural waters using countercurrent chromatography.

Microplastics is known to be ubiquitous in aquatic environment. Quantification of microplastics in natural waters is an important problem of analytical chemistry, the solution of which is needed for the assessment of water quality and potential risks for water inhabitants and consumers. Separation methods play a key role in the correct quantification of microplastics in natural waters. In the present study the applicability of countercurrent chromatography to the continuous-flow separation and preconcentration of microplastics from water samples in rotating coiled column (RCC) using water-oil systems has been demonstrated for the first time. The effect of column rotation speed and mobile phase (water) flow rate on the retention of the stationary (oil) phase in RCC is studied. The retention parameters of 10 vegetable and 2 synthetic oils are determined. Castor, olive, rapeseed, soybean, linseed, sesame, and sunflower oils are found to be applicable to the separation of microplastics from water samples using RCC. Taking as example polyethylene microparticles of different size (40-63, 63-100, and 100-250 µm), the high recovery of microplastics (about 100 %) from aqueous phase into castor and rapeseed oils is shown. The method has been proven to be efficient for the separation of microplastics from simulated fresh and sea natural waters. It may be perspective not only for the quantification of microplastics in natural waters but as well as for the purification of wastewaters containing microplastics.

Regioselective Synthesis of Highly Functionalized 2H-Pyrroles via Dearomative Chlorination of 1H-Pyrroles.

An efficient protocol was developed for the synthesis of highly functionalized 2H-pyrroles. This synthetic approach involves the in situ generation of highly reactive 2,5-dichloro-substituted 2H-pyrroles through dearomative chlorination of the corresponding 1H-pyrroles. The resulting reaction mixture is then treated with various amines, leading to the formation of 2,5-diaminated 2H-pyrroles. Subsequent nucleophilic substitution of fluorine with different N-, O-, and S-nucleophiles allows us to introduce additional functionality into a 2H-pyrrole core. The overall outcome of this reaction sequence is the triple nucleophilic modification of pyrroles. All steps of the sequence were found to be highly efficient, regioselective in the preparation of desired di- and trisubstituted derivatives in up to 96% overall yield. In addition, the computational study of this reaction sequence was carried out using density functional theory (DFT). The results of calculations are in perfect agreement with experimental observations.

A predictive model of super response to cardiac resynchronization therapy in short-term period.

BACKGROUND: The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. METHODS: Patients with QRS ≥ 130 ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6 month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6 month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. RESULTS: Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). CONCLUSION: Our predictive model is able to distinguish patients with a super response to CRT.

Cyclocondensation of 2-(α-Diazoacyl)-2H-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-d]imidazoles.

A diazo approach toward functionalized naphtho[1,2-d]imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2H-azirines giving 5-aryl-4-(α-diazoacyl)-1H-imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations. The reaction proceeds in an unusual manner by cleavage of the azirine C-C bond, allowing for the transfer of the aryl substituent from the arylamidine to the proper position of the key intermediate of naphtho[1,2-d]imidazole synthesis. Under thermolysis conditions, 5-aryl-4-(α-diazoacyl)-1H-imidazoles undergo Wolff rearrangement followed by the selective 6π-cyclization of transient ketene to form 3H-naphtho[1,2-d]imidazoles bearing various substituents in the positions 2,3,4,5,7,8,9. Additionally, variation of the substituents at position 5 of naphtho[1,2-d]imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3H-furo[3',2':3,4]naphtho[1,2-d]imidazole, was easily constructed from methyl 5-hydroxy-3H-naphtho[1,2-d]imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields.

Crystal structure and Hirshfeld surface analysis of (Z)-4-oxo-4-{phen-yl[(thio-phen-2-yl)meth-yl]amino}-but-2-enoic acid.

In the title compound, C15H13NO3S, the mol-ecular conformation is stable with the intra-molecular O-H⋯O hydrogen bond forming a S(7) ring motif. In the crystal, mol-ecules are connected by C-H⋯O hydrogen bonds, forming C(8) chains running along the a-axis direction. Cohesion of the packing is provided by weak van der Waals inter-actions between the chains. A Hirshfeld surface analysis was undertaken to investigate and qu-antify the inter-molecular inter-actions. The thio-phene ring is disordered in a 0.9466 (17):0.0534 (17) ratio over two positions rotated by 180°.

Non-Coagulant Spinning of High-Strength Fibers from Homopolymer Polyacrylonitrile Synthesized via Anionic Polymerisation.

The rheological properties, spinnability, and thermal-oxidative stabilization of high-molecular-weight linear polyacrylonitrile (PAN) homopolymers (molecular weights Mη = 90-500 kg/mol), synthesized via a novel metal-free anionic polymerization method, were investigated to reduce coagulant use, enable solvent recycling, and increase the carbon yield of the resulting carbon fibers. This approach enabled the application of the mechanotropic (non-coagulating) spinning method for homopolymer PAN solutions in a wide range of molecular weights and demonstrated the possibility of achieving a high degree of fiber orientation and reasonable mechanical properties. Rheological analysis revealed a significant increase in solution elasticity (G') with increasing molecular weight, facilitating the choice of optimal deformation rates for effective chain stretching prior to strain-induced phase separation during the eco-friendly spinning of concentrated solutions without using coagulation baths. The possibility of collecting ~80 wt% of the solvent at the first stage of spinning from the as-spun fibers was shown. Transparent, defect-free fibers with a tensile strength of up to 800 MPa and elongation at break of about 20% were spun. Thermal treatment up to 1500 °C yielded carbon fibers with a carbon residue of ~50 wt%, in contrast to ~35 wt% for industrial radically polymerized PAN carbonized under the same conditions.

Crystal structure and Hirshfeld surface analysis of (Z)-4-({[2-(benzo[b]thio-phen-3-yl)cyclo-pent-1-en-1-yl]meth-yl}(phen-yl)amino)-4-oxobut-2-enoic acid.

In the title compound, C24H21NO3S, the cyclopentene ring adopts an envelope conformation. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming ribbons along the a axis. Inter-molecular C-H⋯O hydrogen bonds connect these ribbons to each other, forming layers parallel to the (01) plane. The mol-ecular packing is strengthened by van der Waals inter-actions between the layers. The inter-molecular contacts were qu-anti-fied using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing the relative contributions of the contacts to the crystal packing to be H⋯H 46.0%, C⋯H/H⋯C 21.1%, O⋯H/H⋯O 20.6% and S⋯H/H⋯S 9.0%.