A series of novel substituted isoxazolidine derivatives was synthesized through 1,3-dipolar cycloaddition reactions of α-aryl-N-methyl nitrones with various ethylene moieties, resulting in the formation of isoxazolidine derivatives. The structures of the synthesized compounds were characterized using spectroscopic methods. The [3+2] cycloaddition (32CA) reactions of α-aryl-N-methyl nitrones with diverse ethylene substituents were computed employing Density Functional Theory (DFT) at the B3LYP/6–31G(d) level, upgrading bond parameters. An investigation of the electron localization function (ELF) unveiled the zwitterionic nature of α-aryl-N-methyl nitrones, devoid of pseudoradical or carbenoid centers. Utilization of CDFT indices enabled the prediction of global electronic flux from the strongly nucleophilic α-aryl-N-methyl nitrones to the varied electrophilic ethylene functionalities. Molecular docking and molecular dynamics simulations were conducted on the isoxazolidine derivatives against the EGFR receptor (PDB: 4ZAU). In silico assessment of the synthesized isoxazolidines involved molecular docking, wherein the compound with the highest docking score was subjected to molecular dynamics simulations. Compound 11a, out of the thirty isoxazolidine derivatives, displayed the most substantial binding energy, yielding a g score of -6.57 kcal/mol. These observations highlighted the functional role of amide NH2 and NO2 in the binding process with the target protein, influencing its activity. Furthermore, prediction of ADME drug-likeness properties was performed to identify a suitable candidate.

Abstract: Beetroot (Beta vulgaris L) has been known for being a rich source of phytochemicals, minerals and vitamins. This study presents a model system for how the combination of extrac-tion/chromatography/mass spectrometry and NMR offers an efficient way to profile metabolites in the extracts of a natural product, beetroot . Such combination may lead to the identification of more nutritional or medicinal compounds in natural products, and it is essential for our ongoing investigation to study the selective adsorption/desorption of these metabolites on nanoparticles. The aqueous and organic extracts underwent analyses using UV-vis spectroscopy; GC-MS; LC-MS; 1H, 13C, TOCSY, HSQC, and selective TOCSY NMR experiments. Polar Extract: The two forms of betalain pigment were identified by UV-vis and LC MS. Fourteen amino acids, sucrose, and other compounds among which is riboflavin, were identified by LC-MS. 2D TOCSY showed the spin coupling correlations corresponding to some of these compounds. The HSQC spectrum showed 1H/13C spin correlation in sucrose confirming the high abundance of sucrose in beetroot. Organic Extract: GC-MS data enabled the identification of several compounds including six fatty acid methyl esters (FAME) with higher than, on average, 90% similarity score. Selective TOCSY NMR data showed the spin coupling pattern corresponding to oleic, linoleic, and linolenic fatty acids. 31P NMR spectra indicate that phospholipids exist in both the organic and aqueous phases. Keywords: Beetroot (Beta vulgaris L); Total Correlation Spectroscopy (TOCSY); Gas Chromatog-raphy-Mass Spectrometry (GC-MS); selective TOCSY, Homonuclear single quantum correlation (HSQC); fatty acid methyl esters (FAME).

Today, enhancing food preservation and safety in the spirit of the bioeconomy suggests the use of biodegradable polymers such as poly-L-lactic acid (PLA) in food packaging and the replacement of chemical additives with natural antioxidant/antibacterial agents such as essential oils and their derivatives. Herein a novel carvacrol (CV) @ natural zeolite (NZ) nanohybrid was developed by employing a new vacuum adsorption desorption method which results in the adsorption of a high CV amount on NZ equal to 61.7 %wt. This CV@NZ nanohybrid was successfully dispersed in a PLA/triethyl citrate (TEC) matrix via a melt-extrusion process to obtain PLA/TEC/xCV@NZ nanocomposite films with 5, 10 and 15 CV@NZ %wt. content. PLA/TEC/xNZ films were also de-veloped for comparison. The overall study resulted in a biodegradable active film with the fol-lowing properties: 10%wt. CV@NZ content (PLA/TEC/10CV@NZ), self-healable properties, 22% higher tensile strength and 40% higher elongation at break, 45% higher water barrier and 40% higher oxygen barrier than pure PLA/TEC matrix. This film also provides high CV release content, high CV control release rate as well as significant antioxidant activity and antibacterial activity against the food pathogens Staphylococcus aureus and Salmonella enterica spp. enterica serovar Typhimurium. This film not only succeeds in extending the shelf-life of fresh pork minced, as shown by total variable count measurements in four days, but also prevents lipid oxidation of fresh minced pork and maintains the minced meat in higher nutritional conditions, as revealed by the heme iron content determination, and in a much better and acceptable sensory condition than the commercial packaging paper.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

Poly(hydroxyalkanoates) (PHAs) are currently considered competent candidates to replace traditional plastics in several market sectors. However, commercial PHA grades exhibit unsatisfactory smell that can negatively affect the quality of the final product. The cause of this typical rancid odour is attributed to oxidized cell membrane glycolipids, coming from Gram negative production strains, which remain frequently attached to PHAs granules after extraction. The aim of this research is the development of customised PHA nano-biocomposites for industrial applications containing organo-modified nanoclays with high adsorption properties able to capture volatile compounds responsible of the displeasing fragrance in PHAs. To this end, a methodology for the detection and identification of the key volatiles released due to oxidative degradation of PHAs has been established using a headspace solid-phase microextraction technique. We report the development of nine nano-biocomposite materials based on three types of commercial PHA matrices loaded with three species of nanoclays which represent a different polar behaviour. It has been demonstrated that although the reached outcome effect depends on the volatile nature, natural sepiolite (T2) might result in the most versatile candidate for all PHA matrices selected.

The aim of the work is to study the effect of the 3D printing process on the microstructural and hydrophilic properties of polylactic acid (PLA) samples with various model printing patterns obtained from the black Filament PLA by sequentially applying polymer layers using the FDM (Fused Deposition Modeling) method. X-ray phase analysis revealed partial crystallization of PLA polymer chains in printed samples, which occurs under thermal and mechanical action on the original amorphous PLA filament during 3D printing to varying degrees, depending on the geometry of the pattern and the morphology of its surface. At the same time, IR spectroscopy data indicate the preservation of all intrastructural chemical bonds of polylactide. Measured at the original installation, the values of the wetting edge angles on the surface of the printed samples are in the range φ = 50-60°, which is significantly less than the right angle. This indicates the hydrophilic properties of all samples’ surface. At the same time, the influence of different geometries of model drawings in printed samples was found not only on the morphology of the samples’ surface according to SEM data, but also on its wettability.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

In mammals, Tripartite motif-containing (TRIM) proteins modulate the immune response by coordinating pro-inflammatory related processes such as antiviral restriction, cellular autophagy and inflammasome activation. In fish, TRIM proteins have been reported mainly in cyprinids (e.g., carp, zebrafish) and salmonids (rainbow trout). However, their molecular mechanisms and functions are still being described these animals. Our study focused on characterizing novel TRIM proteins involved in the innate immune response of gill cells from rainbow trout stimulated with LPS or poly(I:C). Also, a fish trial was performed to detect TRIM proteins of rainbow trout after a challenge with Flavobacterium psychrophilum, a salmonid bacterial pathogen. At in vitro level, the results showed that, among several TRIM proteins, OmTRIM25 triggered an LPS-induced expression of pro-inflammatory cytokines (TNF-α2 and IL-1β), suggesting a potential local modulatory function. Moreover, in the fish trial, while OmTRIM25 and finTRIM2 were up-regulated in the gills two days post infection (dpi), IL-1β and TNF-α2 reached their peaks of expression at four- and six-dpi. Finally, after delving into the function of OmTRIM25 by RNA interference (RNAi) gene-silencing, we propose that TRIM proteins such as OmTRIM25 are needed to induce the pro-inflammatory response in the gills of rainbow trout, which confirms their immunomodulatory function.

Many stable water dispersions of various chemical compositions containing bioactive chemical compounds: copper silicate, titanium dioxide and zinc oxide (and other auxiliary substances) were developed and fabricated - they were used for preparation of thin hybrid coatings having very good antimicrobial properties against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and yeast fungus (Candida albicans). Polyester (PES) nonwovens were modified by dip-coating, and PES and cotton fabrics - by dip-coating and coating methods.