A new tetracyclic morpholine-fused [5,1-c]-triazole, (4aS,5S,6aR,10aR,10bR)-5-methoxy-9,9-dimethyl-4a,5,6a,7,10a,10b-hexahydro-12H-[1,3]dioxino[4',5':5,6]pyrano[4,3-b][1,2,3]triazolo[1,5-d][1,4]oxazine, was synthesized via a five-step sequence starting from methyl α-D-glucopyranoside by using as a key step an intramolecular copper(I) cat-alyzed alkyne-azide cycloaddition (CuAAC). The synthesized compound was fully characterized by 1H and 13C NMR, FT-IR, and HRMS.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

New furan, thiophene and triazole oximes were synthesized through several-step reaction paths to investigate their potential for development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Acute OP poisoning is still a challenge in treating patients despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, are blocked by the OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to cholinergic crisis. Oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper we described the synthesis of 63 heterostilbene derivatives out of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents – sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in micromolar range, we identified several oximes as BChE or AChE selective inhibitors with a potential for drug development. Moreover, even oximes were poor reactivators of AChE, four heterocyclic derivatives reactivated the cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had comparable reactivation efficacy to the standard oxime HI-6. In silico analysis and molecular docking studies connected the kinetic data to the structural features of these oximes, and confirmed their productive interactions with the active site of the cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

This work aimed to synthesize new N-rich triazole compounds. In this article we describe the synthesis of three different 1,2,4-triazole-based systems starting from 1,3-diaminoguanidine hydrochloride monohydrate. The structure of the obtained crystals was established by single-crystal X-Ray diffraction. The high nitrogen content of the synthetized compounds makes them building blocks for the application in the High-Energy-Density material science.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research, to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in literature.

In this work SiC-Ti3AlC2 and TiC-Ti3AlC2 composites produced by additive manufacturing are investigated. The fused granules fabrication (FGF) method as one of the material extrusion additive manufacturing (MEAM) technology is used to obtain composite samples. Composites with different ratios between components and different powder:polymer ratios are investigated. The technological features of the additive formation of composites are investigated, as well as their structure and properties. The optimal sintering temperature to form the best mechanical properties for both composites is 1300 °C. The composites have a regulatable porosity. Ti3AlC2 content, sintering temperature, and polymer content in the feedstock are the main parameters that regulates the porosity of FGF samples.

This research investigates the application of Fused Filament Fabrication (FFF) in producing WC-10Co hardmetals, focusing binder formulations and understanding its influence on extrusion force and the influence of printing variables on green density of the samples. By examining the interplay between different binder compositions and backbone contents, the study aims to enhance the mechanical properties of the sintered parts while reducing defects inherent in the printing process. Evidence suggested that formulated feedstocks influenced the hardness of the sintered hardmetal, not due to microstructural changes but to macrostructural responses like macro defects introduced during printing, debinding and sintering of the samples. The results demonstrate the critical role of PP-MA content in improving part density and sintered hardness, suggesting the need for specific thermal debinding protocols tailored to each feedstock. The study provides insights into the formulation of feedstocks for hardmetal FFF, proposing a path toward refining manufacturing processes for better quality and performance of 3D printed hardmetal components.

A number of chemical modifications were carried out in order to synthesize new compounds based on the triterpenoid betulonic acid. Triazolation reactions were carried out for the synthesis of new 1,2,3-triazole derivatives based on betulonic acid. Chemical changes were made on the carbonyl group at the C-3 position of the initial molecule and on the carboxyl and hydroxyl groups at the C-28 position. Chromatographic methods were used to separate and purify the formed products. Spectroscopic (NMR-, mass-) methods were used to establish the structure of synthesized compounds. As a result of the chemical transformations carried out, a number of new derivatives of betulonic acid were obtained. All synthesized compounds were tested for antimicrobial and cytotoxic activity. As a result, compounds with pronounced antimicrobial activity were identified.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

The last series of Raven's standard progressive matrices (SPM-LS) test were studied with respect to its psychometric properties in a series of recent papers. In this paper, the SPM-LS dataset is analyzed with regularized latent class models (RLCM). For dichotomous item response data, an alternative estimation approach for RLCMs is proposed. For polytomous item responses, different alternatives for performing regularized latent class analysis are proposed. The usefulness of the proposed methods is demonstrated in a simulated data illustration and for the SPM-LS dataset. For the SPM-LS dataset, it turned out the regularized latent class model resulted in five partially ordered latent classes.

Current study aims to evaluate the possibilities to increase part strength by optimizing the FFF process parameters. Five different CAD models of parts with same coupling dimensions but different shape inherited from a recent study were converted into test samples with Ultimaker 2 3D printer. The main measure of success was the sample strength, defined as the load at which the first crack in the stressed area of the part appeared. Three different modifications to the FFF process with verified positive effect on interlayer bonding were applied. First modification included raising the extrusion temperature and disabling printed part cooling. Second modification consisted in reduction of the layer thickness. Third modification combined the effects of the first and the second ones. For four out of five shapes tested applied process modifications resulted in significant strengthening of the part. The shape that exhibited the best results was subject to further research by creating special printing mode. The mode included fine-tuning of three technological parameters on different stages of the part fabrication. As result it was possible to increase the part strength by 108% only by tuning printing parameters of the best shape designed with increasing its weight by 8%.

Current paper investigates the influence of hardware setup and parameters of a 3D printing process based on fused filament fabrication (FFF) technology on resulting sample strength. Three-point bending of samples printed with long side oriented along Z axis was used as a measure of the interlayer bonding strength. The same CAD model was converted into NC-programs through same slicing software to be run on four different desktop FFF 3D printers, out of filament of same brand and color. Within all the printers same ranges of layer thickness values from 0.1 to 0.3 mm and feed rates from 25 to 75 mm/s were planned to be varied. All the machines demonstrated statistically almost identical values of maximum flexural strength, however the different machines exhibited maximum sample strength with different combinations of varied parameters. Among all the hardware factors observed, the most important was proved to be extruder type, direct or Bowden. This feature fundamentally changes the nature of studied parameters influence onto the resulting strength of the FFF process. For the extruders of Bowden type the length of flexible guiding tube is of great importance.All the machines demonstrated statistically almost identical values of maximum flexural strength, however the different machines exhibited maximum sample strength with different combinations of varied parameters. Among all the hardware factors observed, the most important was proved to be extruder type, direct or Bowden. This feature fundamentally changes the nature of studied parameters influence onto the resulting strength of the FFF process. For the extruders of Bowden type the length of flexible guiding tube is of great importance.

The paper formulates requirements for a polymer material for molding products from it by fused deposition modeling. A methodology for evaluating the suitability of a polymer or composite of thereof in 3D printing technology has been developed. A graphic representation of the developed methodology in the form of a temperature-shear rate logarithm diagram is proposed. Application of the proposed methodology makes it possible to simplify the development of new materials for 3D printing by fused deposition modeling both at the stage of selecting the components of the polymer composition and at the stage of its subsequent approbation.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Dibenzocycloctynes have emerged as a promising scaffold for bioorthogonal ligation. An important structural aspect that has not been addressed so far is connected with their chirality. Herein, we explore by theoretical and experimental methods this structural aspect that has been so far neglected. First, a computational analysis is conducted and results are used as a guideline for experimental investigation. Next, an array of different experiments (HPLC on chiral columns, chiroptical spectroscopy, X-ray diffraction) for structure elucidation are scrutinized in concert. Finally, this work demonstrates the chirality and the stereodynamic behavior of dibenzocycloctynes and of their triazole adducts with simple azides and uncover their conformational behavior.

Organic compounds that contain poly-triazole are very important intermediates in pharmaceutical and chemical industry. Click chemistry is one of essential reactions that can form C-N bond with high atom economy. The research progress in metals catalyzed Click chemistry of azides and alkynes from the perspective of reaction mechanism is categorized and summarized.

More than 90% of patients affected by mastocytosis are characterized by a somatic point mutation of c-KIT, which induces ligand-independent activation of the receptor and downstream signal triggering, ultimately leading to mast cell proliferation and survival. The most frequent mutation is c-KIT p.D816V, but other rarer mutations can also be found. These mutations often have a very low variant allele frequency (VAF), well below the sensitivity of common next-generation sequencing (NGS) methods used in routine diagnostic panels. Highly sensitive methods are developing for detecting mutations. This review summarizes the current indications on the recommended methods and on how to manage and interpret molecular data for the diagnosis and follow-up of patients with mastocytosis.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Piezoelectric c-axis oriented zinc oxide (ZnO) thin films, from 1.8 up to 6.6 µm thick, have been grown by radio frequency magnetron sputtering technique onto fused silica substrates. A delay line consisting in two interdigital transducers (IDTs) with wavelength λ = 80 µm was photolith-ographically implemented onto the surface of the ZnO layers. Due to the IDTs split finger con-figuration and metallization ratio (0.5), the propagation of both the fundamental, third and nineth harmonic Rayleigh waves is excited; also, three leaky surface acoustic waves (SAWs) were detected travelling at velocity close to that of the longitudinal bulk wave in SiO2. The acoustic waves propagation in ZnO/fused silica was simulated by using 2D finite-element method (FEM) tech-nique to identify the nature of the experimentally detected waves. It turned out that, in addition to the fundamental and harmonic Rayleigh waves, also high-frequency leaky surface waves are ex-cited by the harmonic wavelengths; such modes are identified as leaky-Sezawa (LS) waves under cut-off. The velocity of all the modes was found in good agreement with the theoretically calcu-lated values. The existence of a low-loss region for the Sezawa wave below the cut off was theo-retically predicted and experimentally assessed.

With the advancement of Additive Manufacturing and its applications in various industrial segments, it becomes increasingly important to investigate the processability parameters associated with nano-reinforcement. This study examines the influence of infill parameters, such as patterns (hexagonal, triangular and concentric), shape (solid and honeycomb) and concentrations by mass of Carbon Nanotubes (CNTs) at 1.0 wt% and 2.0 wt% on the mechanical compression properties of the 3D printed material. In this sense, nanocomposites based on Polylactic Acid (PLA) matrix nano-reinforced by CNTs were characterized using the Scanning Electron Microscopy -SEM, X-ray Diffraction, Raman Spectroscopy techniques and mechanical analysis. The mechanical properties of both the matrix and the nanocomposites were determined through mechanical compression tests, in accordance with [1]. SEM revealed compacted regions, voids, and detachment in the structures. XRD characterization indicated PLA predominantly amorphous nature, while CNTs exhibited characteristic diffractions of carbon nanotubes. Raman characterization showcased bands and characteristic vibrations of CNTs and PLA, nanocomposites' vibrational modes combine those of CNTs and PLA. Mechanical compression analysis indicates a direct influence of infill pattern, shape, and nano-reinforcement. The triangle pattern outperformed other patterns, exhibiting a 15.03% increase compared to concentric and 8.8% compared to hexagon infill. In nanocomposites, all showed higher compressive strength than the matrix. For PLA/1.0%CNTs, strength was 16.8%, and for PLA/2.0%CNTs, it reached 39.2%. In honeycomb shapes with infill variations, the triangular pattern excelled with a 0.97% increase over concentric and 6.12% over hexagon patterns. Honeycomb results indicate a 59.6% increase for (PLA/1.0%CNTs) and a 0.48% increase for (PLA/2.0%CNTs) compared to the matrix. This study highlights 3D printing parameters, emphasizing the effectiveness of the triangular pattern and the enhanced strength with the addition of CNTs, providing insights to enhance products manufactured through Additive Manufacturing.

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

Dual generalized commutative quaternions have broad application prospects in many fields. Additionally, the matrix equation AXB = C has important applications in mathematics and engineering, especially in control systems, economics, computer science, and other disciplines. However, research on the matrix equation AXB = C over the dual generalized commutative quaternions remains relatively insufficient. In this paper, we derive the necessary and sufficient conditions for the solvability of the dual generalized commutative quaternion matrix equation AXB = C. Furthermore, we provide the general solution expression for this matrix equation, when it is solvable. Finally, a numerical algorithm and an example are provided to confirm the reliability of the main conclusions.

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial in mitigating oxidative stress in a hostile environment. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella abortus. In this study, to determine whether the inhibition of catalase can inhibit the intracellular growth of Brucella (B.) abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Aside from that, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced B. abortus proliferation within the spleen and liver of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by lowered levels of TNF-α, IL-6, IL-10, and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lan-thanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculat-ed-experimental IR and Raman spectra. The best DFT method appears to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. Potential free radical scavenging activity of both, ligand and complex, was investigated in several radical-generating model systems. Potential mechanisms of antioxidant action (hydrogen atom transfer – HAT and single electron transfer - SET) were elucidated.

Wheat is one of the global strategic crops and ranks third in terms of cereals production. Wheat crop is exposed to many fungal infections during the cultivation stages, some of which have the ability to secrete numbers of toxic secondary metabolites that threaten the quality of grains, consumer health, producer economics and global trade exchange. Fifty-four random samples were collected from wheat which originated from different countries. The samples included 14 of soft wheat to study the extent of their contamination with Deoxynivalenol (DON) and T-2 toxin by auto-ELISA technology and r-biopharm Microtiter plate. All samples were contaminated with DON toxin except one sample, and the contamination average ranged between 40.7 and 1018.8 µg kg-1. The highest contamination rates were in Lithuanian and the lowest in Indian wheat. Meanwhile the highest average level of T-2 toxin contamination was in Lithuanian wheat grains with a rate of 377.4µg kg-1 and the lowest in Polish wheat with an average of 115.3µg kg-1. GC-MS/MS and multiple reaction monitoring mode (MRM), was used to detect 15 triazole derivatives in collected samples, which may be used to combat fungal diseases on wheat during the growing season. Only 9 derivatives were found; Simeconazole, Penconazole, Hexaconazole, Cyproconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole. These derivatives varied according to the origin of wheat samples as well as their its concentration whereas, another 6 derivatives were not detected in all samples. A direct inverse relationship was found between the DON concentration in the samples and the residues of Simeconazole, Penconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole and the T-2 toxin showed the same relationship except for Tebuconazole. The safe and rational use of some triazole derivatives may be a new approach and a promising strategy not only to reduce plant diseases and their problems, but also to get rid of some mycotoxins as contaminates.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

This study aims to evaluate the effectiveness of inactivating Salmonella enteritidis in fresh chicken breast by irradiation using a combination of short-wave UV (0, 3, 6, 9, 12 and 15 J / cm2) and a natural antimicrobial such as caffeine (0, 5, 10, 15 and 20 nM/g) as alternative proposals to conventional techniques to reduce pathogens in food. The temperatures used were from 2 to 22°C. The most suitable models were double Weibull in 60% of cases with an adjustment of R2 0.9903-0.9553 and Weibull + cola, in 46.67%, with an adjustment of R2 of 0.9998-0.9981. Noting that the most effective combination in the reduction of Salmonella was 12 J/cm2 of UV light and 15 nM/g of caffeine, with a reduction of 6 CFU/g and an inactivation rate of 0.72. The synergistic effect was observed by increasing caffeine and UV light. Furthermore, the physic-chemical characteristics of the food matrix were not affected by the combination of both technologies. Therefore, these results suggest that this combination can be used in the food industry to effectively inactivate Salmonella enteritidis, without deteriorating product quality.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Polyetheretherketone is a promising material for implants due to its good mechanical properties and excellent biocompatibility. Its accessibility to a wide range of applications is facilitated by the ability to process it with an easy-to-use manufacturing process such as Fused Filament Fabrication. The elimination of disadvantages associated with the manufacturing process, such as a poor surface quality, is a main challenge to deal with. As part of the mass finishing process, centrifugal disc finishing has demonstrated good results in surface optimization, making it a promising candidate for post-processing of additively manufactured parts. The objective of this study is to identify the key parameters of the centrifugal disc finishing process on the waviness of additively manufactured PEEK specimen, which has not been investigated yet. Waviness of the specimen was investigated by means of confocal laser scanning microscopy (CLSM), while weight loss was additionally tracked. Six parameters were investigated: type, amount and speed of media, use of compound, amount of water and time. Type of media, time and speed were found to significantly influence waviness reduction and weight loss. Surface electron microscopy images demonstrated the additional effects of deburring and corner rounding. Results on previous studies with specimens made of metal showed similar results. Further investigation is required to optimise waviness reduction and polish parts in a second post-processing step.

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

As part of valorisation of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a-v bearing 1,2,3-triazole moieties were designed and synthesized by treating a previously azide 4 prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues 18a-v were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes; and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained notably against L. monocytogenes. Compounds 18d, 18g and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. Molecular docking study was performed to explore the binding mode of the most active derivatives against the target protein from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor to the experimental data.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

There are few longitudinal studies on the association between dietary vitamin C and sleep disorders. The aim of this study was to investigate the association between dietary vitamin C intake and various types of sleep disorders, including sleep apnea and insomnia, as well as recommended dietary intakes. A total of 68,221 participants from the UK Biobank were enrolled in the study. Dietary vitamin C intake was calculated by a 24-hour dietary recall questionnaire. We used Cox regression model to assess the association between dietary vitamin C and sleep disorders and restricted cubic spline models to explore potential nonlinear relationships. Stratified analyses and sensitivity analyses were also performed to further test the results. The results showed that vitamin C intake at the Q4 level (132.88-191.51 mg/d) was significantly protective against sleep disorders with an HR (95% CI) of 0.78 (0.65-0.94), and against sleep apnea with an HR (95% CI) of 0.75 (0.62-0.92). The protective effect remained significant in stratified analyses of men and age ≤60 years, and the results were robust in sensitivity analyses. Adequate dietary vitamin C intake may have a protective effect in preventing sleep disorders.

This work investigates how the user-controlled parameters of the 3D printing process define temperature conditions on the boundary between layers of the part being fabricated and how these conditions influence the structure and strength of the part. The process studied is fused filament fabrication with a desktop 3D printer and the material utilized is PLA (polylactic acid). As a characteristic of the part strength the fracture load in the case of a three-point bend and calculated related stress were used. During the printing process parts were oriented with the long side along the Z axis, thus, in the bend tests, the maximum stress occurred orthogonally to the layers. During the fabrication process, temperature distribution on the sample surface was monitored with thermal imager. Sample mesostructure was analyzed using SEM. The influence of the extrusion temperature, the intensity of part cooling, the printing speed and the time between printing individual layers were considered. The influence of all the parameters can be expressed through two generalizing factors: the temperature of the previous layer and the flow efficiency, determining the ratio of the amount of extruded plastic to the calculated. A regression model was proposed that describes the effect of the two factors on the printed part strength. Along with interlayer bonding strength, these two factors determine the formation of the part mesostructure (the geometry of the boundaries between individual threads). It is shown that the optimization of the process parameters responsible for temperature conditions makes it possible to approximate the strength of the interlayer cohesion to the bulk material strength.

The current paper is studying the influence of geometrical parameters of the FDM (FFF) 3D printing process on printed part strength for open source desktop 3D printers and the most popular material used for that purpose, i.e. PLA (polylactic acid). The study was conducted using a set of different nozzles (0.4, 0.6 and 0.8 mm) and a range of layer heights from the minimum to maximum physical limits of the machine. To assess print strength, a novel assessment method is proposed. A tubular sample is loaded in the weakest direction (across layers) in a three-point bending fixture. To explain the results obtained, a mesostructure evaluation through SEM scans of the samples were used. A significant influence of geometric process parameters was detected on sample mesostructure and, consequently, on sample strength.

Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, which contributes significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.

The existences of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both of the total interaction energies of S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in the complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes.

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and the safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked both by cytotoxicity assays and flow cytometry.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

The endocannabinoid system (ECS) is a complex neuromodulatory network in the human body that have enormous impact in developing the central nervous system, as well as modulates various physiological processes. The ECS is made up of anandamide, 2-arachidonoylglycerol (2-AG), which are responsible for the synthesis and degradation of endocannabinoids, and enzymes such as FAAH and MAGL ensures the precise control over endocannabinoid levels. The ECS relies on CB1 receptors found in the central nervous system (CNS), and CB2 receptors found in the peripheral nervous system and immune cells. Dysregulation of the ECS has been associated with several health conditions, prompting investigations into its association with phytocannabinoids to harness their therapeutic potential. The ECS is intricately linked with the nervous system, and it is known to modulate neuronal activities in the CNS, influencing pain and mood modulation. The ECS is also associated with neuropathies-peripheral nerve damage leading to symptoms such as weakness, numbness and pain as evidenced in diabetic neuropathy, Guillain-Barré Syndrome, carpal tunnel syndrome, peripheral neuropathy, and postherpetic neuralgia. The focus of this review is on the interplay between 2-arachidonoylglycerol and anandamide amidohydrolase in neuropathy, elucidating their roles in pain regulation, inflammation, and specific neuropathies. The knowledge generated is expected to have broad implications, providing comprehensive insights into neuropathic conditions and how to improve on them. Ultimately, this understanding may lead to more effective treatments and improved quality of life for individuals affected by these conditions.

This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries have been tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance have been determined. Results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with previous studies results, to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Novel 1,2,3-triazole compounds 3–4 were synthesised via the regioselective addition and cyclization reaction of 1,1-enediamines (EDAMs) 1 with p-methylbenzenesulfonyl azide (TsN₃) 2 in 1,4-dioxane at refluxing for 5 hours. As a result, 1,2,3-triazoles 3–4 can be easily and efficiently obtained via catalyst-free click chemistry. The reactions have some advantages such as metal-free catalyst, excellent yield, inexpensive raw materials, and convenient final treatment.

The Great Reset has been presented by the World Economic Forum (WEF) in response to the COVID-19 pandemic in 2022 as a model through which a “stakeholder economy” would achieve “resilient, equitable and sustainable” economic, social and environmental goals. A more equitable distribution of resources, better working conditions, and ecological transitions are included in a social, economic and environmental reform agenda. This article raises the question of whether the Great Reset project should be interpreted as a “realistic utopia” and what is its reform potential. In an attempt to answer the question of whether the Great Reset as a realist utopia is consistent with the current state of science and philosophy, the article re-examines the idea of utopia in the light of recent philosophical and scientific approaches, such as critical realism in philosophy, so-cial systems theory in sociology and complexity theory in science. A comparative conceptual analysis is carried out and discussed introducing the idea of a realist utopia in Rawls' theory of justice as fairness. In the final discussion, some doubts are raised about the logical coherence, rigor of scientific theorizing, policy prescriptions, and predictive potential of the Great Reset emerging paradigm. It is concluded that utopian projects of radical reform can become realistic when they offer explanations of the deep structural changes that underlie social and economic evolution, drawing from these explanations the policy implications and prescription that can support struc-tural changes, rather than from assumed long-term effects of exogenous shocks or “black swan” events such as the COVID-19 pandemic.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Fused silica glass is a material with outstanding mechanical, thermal and optical properties. Being a brittle material, it is challenging to shape. In the last decade, the manufacturing of monolithic flexible mechanisms in fused silica has evolved with the femtosecond laser-assisted etching process. However, instrumenting those structures is demanding. To address this obstacle, this article proposes to inscribe a Bragg Grating sensor inside a flexure and interface it with an optical fibre to record the strain using a spectrum analyzer. The strain sensitivity of this Bragg Grating sensor is characterized at 1.2 pm/μϵ (1 μϵ = 1 microstrain). Among other applications, deformation sensing can be used to record a force. Its use as a micro-force sensor is estimated. The sensor resolution is limited by our recording equipment to 30 μN over a measurement range above 10 mN. This technology can offer opportunities for surgery applications or others where precision and stability in harsh environments are required.

Oxygen based heterocyclic moieties hold an ample range of therapeutic activities. Heterocyclic molecules are nominated as vital components of an extensive array of structural motifs with both biological and pharmaceutical significance. The oxygen-based scaffolds act as anticancer candidates and are also present in numerous phytomolecules viz; irinotecan, camptothecin, topotecan, taxol, taxotere, podophylotoxin, etoposide, daunorubicin and teniposide. The architectural design of numerous structural motifs for amelioration of cancer has become progressively amplified in recent past years. Until now presently there is no strategic treatment which is so capable that can cure cancer from its roots. Henceforth, it is very indispensible to design novel anticancer structural motifs with least side effects. The oxygen containing heterocyclic scaffolds includes flavonoids, pyrans, xanthones and coumarins are of utmost importance in medical chemistry for the mitigation of cancer. This assemblage offers several recent developments as anticancer oxygen containing heterocyclic molecules all-round the globe and attracted the structural motifs of auspicious molecules, along with their mechanistic insights, IC50 values, structure–activity relationships, and molecular docking studies. The encouraging properties discovered by these oxygen-based scaffolds unconditionally engaging them at frontline in invention of potential drug candidates. Consequently, these probably will be of amazing attention to scientists working on the design and synthesis of antitumor candidates.

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19, that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical and laboratory characteristics between children diagnosed with MIS-C who were admitted to the PICU or did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Patient’s demographic, clinical and laboratory data, were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR:12.89, 95%CI: 1.35-123.41, p-value=0.03) and cardiological involvement (OR:34.55, 95%CI: 2.2-541.91, p-value=0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 hours from admission, D-dimer levels higher than 4μg/mL and decreased Left Ventricular Ejection Fraction were associated with an increased risk of PICU admission (OR:7.95, 95%CI:1.48-42.78, p-value=0.02 and OR=1.28, 95%CI:1.07-1.53, p-value=0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value=0.005) and were hospitalized for more days, than children in the pediatric wards (median length of stay (IQR): 20 (15,28) days vs. 8.5 (6, 14) days, p-value&lt;0.001). Conclusions: In the present study, cardiovascular, hepatic involvement and increased D-dimer levels in children with MIS-C were associated with admission to the PICU.

We hereby describe an efficient method for the preparation of a series of new 1-substituted 1,2,3-triazole-based acetaminophen derivatives through a clean, good-yielding, simple, and expeditious procedure based on the O-propargylation reaction of the acetaminophen (APAP) obtained from expired commercial tablets and the CuBr(PPh3)3-catalyzed Huisgen reaction be-tween O-propargylated APAP and diverse organoazides prepared from commercially available anilines as available starting reagents. An interesting nitric oxide-releasing 1,2,3-triazole hybrid of APAP was also obtained easily using the developed method. The structures of the designed hybrid compounds, which are expected to be pharmacologically active, were fully characterized by FT-IR, 1H- and 13C-NMR and are reported for the first time. According to the in-silico studies performed in this work and literature analysis, these hybrids are interesting models in search of new pharmacological nontoxic agents endowed with anti-inflammatory and anticancer properties.

This research investigates the microstructure and mechanical behaviour of a polylactic acid (PLA)-iron (PLI) composite designed to enable magnetic actuation. Tensile specimens of PLI are produced through Fused Filament Fabrication, incorporating diverse printing angles ranging from 0° to 90°, thereby facilitating the creation of a variety of layups. The microstructure of these 3D-printed composites is analysed using X-ray micro-tomography. Furthermore, the tensile mechanical properties of all composites are evaluated, and the findings are deliberated in relation to the conditions of the printing angle. Additionally, the fractography of broken specimens is examined using Scanning Electron Microscopy. The findings indicate that the printing angle plays a significant role in influencing the tensile properties of the 3D-printed PLI composites, particularly in adjusting mechanical anisotropy. Moreover, an optimal layup of 45°/45° is attained, resulting in an enhanced ranking of the tensile performance. These findings related to 3D-printed PLI composites present a cost-efficient option for manufacturing bio-sourced light-adaptive composites through 3D printing, enabling the generation of intricate magnetic actuation performance.

The possibility of using additive manufacturing (AM) in the medicine area has created a new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU), which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

Different polyurethanes (PUs) were synthesized with polycarbonate polyols of molecular weights 500, 1000 and 2000 Da. Their self-healing abilities at 20 °C were tested and their structural, thermal, and mechanical properties were analyzed. The PUs made with polycarbonates of molecular weights 500 (YC500) and 1000 Da (YC1000) exhibited self-healing at 20 °C and the self-healing time of YC1000 was the shortest. The high mobility of the short polymeric chains, the absence of crystallinity and the low degree of micro-phase separation favored self-healing at 20 °C in YC500. However, the presence of tack and the existence of allophanate species and urethane-carbonate and urea-carbonate hydrogen bonds disfavored self-healing. Consequently, the self-healing time at 20 °C of YC500 was longer than expected. On the other hand, YC1000 exhibited an “equilibrium” between the urethane-carbonate and urea-carbonate hydrogen bonds and carbonate-carbonate interactions among the soft segments, so a particular structural order was produced which was associated to its fastest self-healing at 20 °C. The PU made with the polycarbonate of molecular weight 2000 Da did not exhibit self-healing at 20 °C because its significant micro-phase separation and the presence of semi-crystalline soft domains.

Stage IV grade C localized periodontitis (pre-puberal localized aggressive periodontitis/LPP), an extremely rare form of periodontal disease, occurs in otherwise healthy individuals (no signs of dental plaque/calculus) due a hyper-aggressive auto-immune response to high periodontopathic bacteria levels. Methods: A 4-year-old Caucasian girl with unusual high mobility of temporary lower left canine and localized gingival inflammation was misrecognized by multiple clinicians (initially diagnosed with hypophosphatasia, genetic and metabolic disorders, all turning negative), over a period of 4-6 month, despite initial radiographs showing clear pathognomonic signs. LPP diagnostic was made by the last clinician, but by now the tooth was lost. Similar inflammation signs appeared around the lower temporary right canine. X-ray examination showed similar bone and periodontal loss as previously seen, while periodontopathic bacteria tested highly positive. The patient received both mechanical cleaning and ten days systemic antibiotic treatment (Augmentin and Metronidazole). Results: Two months after, inflammation signs disappeared, with periodontal regeneration radiologically present, and only small periodontopathic bacteria precursors concentrations. Conclusions: Despite initial periodontal loss, an adequate treatment can keep under control an LPP disease. Moreover, bone and periodontal regeneration appears if periodontopathic bacteria scores are kept lower, showing the importance of fast adequate diagnostic and treatment.

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

Solar pasteurization, as a means of treating milk in remote rural areas without electrical power, is based on using solar energy to thermally inactivate pathogenic microorganisms at temperatures below the boiling point to maintain or improve milk quality. A solar milk pasteurizer of flat‐plate water‐heating glass acting as the solar collector, connected to a stainless-steel cylindrical milk vat, was constructed and evaluated in Navrongo, in the tropical savanna zone of Ghana, West Africa. The novel approach taken in this project is to integrate the solar collection and heat exchanger into a single unit using materials and fabrication techniques readily available in the developing world. The vat comprises a 1.5 mm thick stainless steel cylindrical tank, a 2.2 cm wide hot water jacket, and an outer layer of 5.0 mm thick aluminium foil insulation. Hot water produced by the collector was used for pasteurizing milk. The optimum quantity of milk that this device could pasteurize under the study conditions was 8 L. The device could pasteurize raw milk to a maximum temperature of 74 °C at 14:00 h GMT. The ambient temperature during the pasteurization ranged from 30 °C to 43 °C. The microbial analysis before and after the pasteurization was done, and the result shows that the total bacteria count before pasteurization was 6.6x10⁶ log CFU/mL per unit volume, and the total bacteria count after pasteurization was 1.0x10² log CFU/mL. By acceptable standards, the total bacteria count after pasteurization is within a safe range for consumption, and coliform counts were negative. The solar milk pasteurization system is cost-effective. Hence, it is appropriate for milk producers in arid pastoral areas without electricity to adopt the solar pasteurizer as an alternative to firewood as a fuel source for milk pasteurization. This approach can potentially create a cottage industry that may also play a crucial role as a water treatment technology that will improve the health of rural populations.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

In this paper, several two-dimensional clustering scenarios are given. In those scenarios, soft partitioning clustering algorithms (Fuzzy C-means (FCM) and Possibilistic c-means (PCM)) are applied. Afterward, VAT is used to investigate the clustering tendency visually, and then in order of checking cluster validation, three types of indices (e.g., PC, DI, and DBI) were used. After observing the clustering algorithms, it was evident that each of them has its limitations; however, PCM is more robust to noise than FCM as in case of FCM a noise point has to be considered as a member of any of the cluster.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Abstract: Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed.

In this paper, the fatigue response of Fused Filament Fabrication (FFF) Acrylonitrile butadiene styrene (ABS) parts is studied. Different building parameters (layer height, nozzle diameter, infill density, and printing speed) were chosen to study their influence on the lifespan of cylindrical specimens according to a design of experiments (DOE) using the Taguchi methodology. The same DOE was applied on two different specimen sets using two different infill patterns: rectilinear and honeycomb. The results show that infill density is the most important parameter for both studied patterns. The specimens manufactured with the honeycomb pattern show longer lifespans. The best parameter set associated to that infill was chosen for a second experimental phase, in which the specimens were tested under different maximum bending stresses to construct the Wöhler curve associated to this 3D printing configuration. The results of this study are useful to design and manufacture ABS end-use parts that are expected to work under oscillating periodic loads.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

The current work is dedicated to the search for new high-energy materials (HEMs) with improved characteristics which are gained through agglomeration with salts. The research was performed by Becke’s three-parameter hybrid functional approach with non-local correlation provided by Lee, Yang, and Parr and cc-pVTZ basis set. The geometry, total energy, and heat of formation of the most stable compounds forming due to 3-amino-5-[(2, 4, 6-trinitrophenyl) amino]-1H-1, 2, 4-triazole (APATO) within salts selected were obtained to foresee its influence on resistance to shock stimuli, detonation pressure, and velocity of the materials under study. Results obtained allow us to foresee that only agglomeration with precise salts could lead to significant improvement in the stability of the specific high-energy materials and the resistance to shock stimuli. We also show that the agglomeration leads to better energetic properties of the above compound, although the improvement could be insignificant in some cases.

This study presents the development of a diglycidyl monomer containing two imine groups that can act as dynamic and reversible bonds. During the curing of the monomer with two different amine hardeners, we confirmed the formation of new imine groups due to the transamination reaction, not reported before, between the imine groups of the diepoxy monomer with the amine groups of the hardener. The effect of this structural change is observed for the first time in the stress relaxation behavior, resulting in the overlapping of two different relaxation modes. The analytical modelling could extract two distinct characteristic relaxation times using a double-element Maxwell model. A second characterization of the stress relaxation process by frequency sweep experiments was performed to corroborate the results obtained, confirming speedy stress relaxation. Acid-catalyzed hydrolysis was performed on the studied materials, demonstrating the complete degradation of the network. We finally confirmed that the synthesized diepoxy compound is suitable for preparing carbon fiber-reinforced composite materials, demonstrating easy fiber impregnation, fast reshaping and especially a total degradation of the polymer matrix that allows the recovery of the carbon fibers in mild conditions. This epoxy-amine system is an excellent candidate for overcoming the traditional limits of thermosets in preparing fiber-reinforced composites.

Negative temperature coefficient (NTC) materials are usually based on ceramic semiconductors and electrons are involved in their transport mechanism. A new type of NTC material, adequate for alternating current (AC) applications, is represented by zeolites. Indeed, zeolites are single-charge carrier ionic conductors with a temperature-dependent electrical conductivity. In particular, electrical transport in zeolites is due to the monovalent charge-balancing cations, like K⁺, capable of hopping between negatively charged sites in the aluminosilicate framework. Owing to the highly non-linear electrical behavior of the traditional electronic NTC materials, the possibility to have alternative types of materials, showing linearity in the electrical behavior, is very desirable. Among different zeolites, the natural clinoptilolite has been selected for investigating the NTC behavior since it is characterized by high zeolite content, convenient Si/Al atomic ratio, good mechanical strength, due to its compact microstructure, and low toxicity. Clinoptilolite has shown a rapid and quite reversible impedance change under heating, characterized by a linear dependence on temperature. X-ray diffraction (XRD) has been used to identify the natural zeolite, to establish all types of crystalline phases present in the mineral, and to investigate the thermal stability of these phases up to 150°C. X-ray photoelectron spectroscopy (XPS) analysis has been used for the chemical characterization of the natural clinoptilolite sample, providing important information on the cationic content and framework composition. In addition, since electrical transport takes place in the zeolite free-volume, a Brunauer–Emmett–Teller (BET) analysis of the mineral has been also performed.

For the set of probability measures ${\sf I}(X)$, where $X$ is a compact Hausdorff space, we propose a new way to introduce the topology by using open subsets of the space $X$. Then, among other things, we give a new proof that for a compact Hausdorff space $X$ the space ${\sf I}(X)$ is also a compact Hausdorff space. For a Tychonoff space $X$, we consider the topological space ${\sf I_{\tau}}(X)$ of $\tau$-smooth idempotent probability measures on $X$,and show that the space ${\sf I_{\tau}}(X)$ is \v{C}ech-complete if and only if the given space $X$ is \v{C}ech-complete.

This report describes the collection of a large dataset (6930 measurement) on dimensional error in the fused deposition modeling (FDM) additive manufacturing process for full-density parts. Three different print orientations were studied, as well as seven raster angles (0°, 15°, 30°, 45°, 60°, 75°, and 90°) for the rectilinear infill pattern. All measurements were replicated ten times on ten different samples to ensure a comprehensive dataset. Eleven polymer materials were considered: acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), high-temperature PLA, wood-composite PLA, carbon-fiber-composite PLA, copper-composite PLA, aluminum-composite PLA, high-impact polystyrene (HIPS), polyethylene terephthalate glycol-enhanced (PETG), polycarbonate, and synthetic polyamide (nylon). The samples were ASTM-standard impact testing samples, since this geometry allows the measurement of error on three different scales; the nominal dimensions were 3.25mm thick, 63.5mm long, and 12.7mm wide. This dataset is intended to give engineers and product designers a benchmark for judging the accuracy and repeatability of the FDM process for use in manufacturing of end-user products.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

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.

This paper investigates the influence of sample size and layer height on the elastic modulus of samples 3D printed by fused filament fabrication (FFF). Cubic samples of different sizes from either a stiff thermoplastic polymer (polycarbonate (PC)) or a soft polymer (thermoplastic polyurethane (TPU)) were printed at three different layer heights: 0.1 mm, 0.2 mm, and 0.4 mm. The samples were imaged using micro-computed tomography to visualize porosity and tested under compression. The results indicate that the elastic modulus of TPU varied with sample size, demonstrating size effects due to high porosity. In contrast, PC samples had a low void volume fraction and did not demonstrate statistically significant size effects on the elastic modulus. The variations in elastic modulus due to layer height were statistically significant for both materials. The highest elastic modulus was observed at 0.2 mm layer height for both materials across different sample sizes, which can be attributed to low void volume fractions. The study develops process-structure-property relations for PC and TPU samples manufactured by FFF. It provides new insights into the design guidelines for FFF based on the size effects. The results indicate that variations in mechanical properties due to size effects must be considered during the design stage for TPU to accurately predict the material’s behavior. Additionally, the locations of the printed parts that are subjected to higher loads should be printed closer to the heated print bed due to the lower void volume fraction observed in the section of the samples printed adjacent to the heated print bed.

Abstract: Polylactic acid (PLA) is brittle in nature with extensive deformation property. For improvement of the end-use quality, it is of significant importance to enhance the producibility of fused deposition modeling (FDM)-printed objects in PLA. The purpose of this investigation is to boost toughness and to reduce the production cost of the FDM-printed tensile test samples with the desired part thickness. To attain the research purpose number of experiments are designed and analyzed by the Response Surface Method (RSM). The statistical analysis is performed to deal with this concern considering layer thickness, infill percentage, and extruder temperature as controlled factors. The tensile test specimens are printed based on the designed experiments, and the tensile strength tests are conducted by SANTAM 150 universal testing machine based on ASTM D638. The honeycomb internal fill pattern is applied for the production of light-weight and high-strength specimens. The area under Force- Extension curve up to fracture is acquired as the toughness of the printed specimens. This study also developed a modeling process using ANN and ANN-GA techniques for developing an accurate estimation for toughness, part thickness, and production cost as dependant variables. Results were evaluated by correlation coefficient and RMSE values. According to the modeling results, ANN-GA as a hybrid ML technique could successfully improve the accuracy of modeling about 7.5, 11.5 and 4.5 % for toughness, part thickness, and production cost, respectively, in comparison with those for the single ANN method. In the other side, the optimization results confirm that the optimized specimen is cost-effective and able to comparatively undergo deformation, which develops the usability of printed PLA objects. The research is accomplished under the constraints of PLA compatibility with existing fused deposition modeling setup without changing the functional hardware/software of the machine. Although the mechanical properties and dimensional accuracy of PLA have already been studied, there is little literature on the toughness of the printed PLA with honeycomb internal fill pattern.

The parts obtained by FFF technology are anisotropic in any direction; while the whole part constitutes out of layers, each of the layers include one or more perimeters of shell and the infill with density from 0 to 100%. Mechanical performance of FFF parts depends on its shape, orientation, constitution and 3D printing parameters. A classification for shapes of parts obtained by FFF and stressed during its operation is provided. For the most questionable class (parts with interrupted shell critically stressed on interlayer boundaries) a representative sample and testing apparatus is developed. Different approaches to the sample shape modification were applied and tested. The part shape optimization resulted in increment of the force, required to fracture the part from 483 to 1096 N.

Additive manufacturing (AM) are used in several industries such as automotive, aerospace, and medical sciences. One of the most common devices used in additive manufacturing is fused deposition modeling (FDM) 3D printers. This fabrication method has different inputs that affect the quality of the parts. In this research, the bending fatigue properties of polylactic acid (PLA) biomaterial made with a 3D printer are investigated. To demonstrate the influence of printing parameters on fatigue lifetime, standard specimens with nozzle diameters of 0.2-0.6 mm, extruder temperature of 180-240°C, and print speed of 5-15 mm/s were printed. After performing fully-reversed bending fatigue tests, it was found that printed specimens at 180°C have the best fatigue lifetime in most cases. Accordingly, fatigue behavior improved by reducing the nozzle diameter. Printing at lower temperatures also improved fatigue lifetime. The printing speed affected the slope of the S-N diagram, known as the fatigue strength exponent.

The main purpose of this paper is to present a system to detect extrusion failures in Fused Deposition Modelling (FDM) 3D printers by sensing that the filament is moving forward properly. After several years using these kind of machines, authors detected that there is not any system to detect the main problem in FDM machines. Authors thought in different sensors and used the Weighted Objectives Method, one of the most common evaluation methods, for comparing design concepts based on an overall value per design concept. Taking into account the obtained scores of each specification, the best choice for this work is the optical encoder. Once the sensor is chosen, it is necessary to design de part where it will be installed without interfering with the normal function of the machine. To do it, photogrammetry scanning methodology was employed. The developed device perfectly detects the advance of the filament without affecting the normal operation of the machine. Also, it is achieved the primary objective of the system, avoiding loss of material, energy and mechanical wear, keeping the premise of making a low-cost product that does not significantly increase the cost of the machine. This development has made it possible to use the printer with remains coil filament, which were not spent because they were not sufficient to complete an impression and also printing models in two colours with only one extruder.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

Suzuki cross-coupling reaction has developed one of the furthermost effectual approaches for the synthesis of biaryls or substituted aromatic moieties from aryl halides and arylboronic acids with a palladium-catalyst in the past two era’s. Herein, Pd-free layered double hydroxide containing nickel catalysts were prepared by co-precipitation method under ultrasonic irradiation and N2 atmosphere with different molar ratios of Ni: Mg: Al and coded as (1NiLDHs-Dr), (1.5NiLDHs-Dr) and (2NiLDHs-Dr). A series of reduced catalysts under 5%H2/N2 at different temperatures were coded as 1NiLDHs-R200, 1.5NiLDHs-R200 and 2NiLDHs-R200. As-synthesized 2NiLDHs-Dr was the superlative catalyst when coupling different aryl halides with different boronic acids derivatives. Deep investigation of all catalysts was done using different techniques such as inductively coupled plasma optical emission spectroscopy (ICP-OES), x-ray photoelectron spectroscopy (XPS), powder x-ray diffraction (XRD), thermogravimetric analyses (TGA), Fourier transfer infrared (FTIR), scanning electron microscope (SEM) connected with energy dispersive x-ray (EDX) and N2-physisorption at -196 ℃. The results attained verified that ɑ-Ni(OH)2 was fashioned for 2NiLDHs-Dr catalyst and the enclosure of nickel ions in the cationic sheet of layered structure were responsible for the fascinating catalytic efficacy rather than the basic nature of material. The Ni-containing LDHs catalysts encourage forthcoming studies in Pd-free catalyzed C-C coupling reactions.

Background: The predictive value of changes in C-reactive protein (CRP), procalcitonin and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. This study aims to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of patients admitted to the intensive care unit (ICU) with a diagnosis of pneumosepsis and pneumonia-related septic shock, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Methods: The study analyzed the demographic data, Charlson Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65 years), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores of 230 patients admitted to the ICU with a diagnosis of pneumosepsis and pneumonia-related septic shock between April 1, 2022, and December 31, 2023. The levels of CRP, procalcitonin, and leukocytes were also recorded and analyzed to assess their impact on 1-month and 3-month mortality outcomes. Results: According to multivariate logistic regression analysis, low BMI, male gender, high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p<0.05). An elevated SOFA score was associated with 1-month mortality, while advanced age was related to 3-month mortality (p<0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both 1-month and 3-month mortality cases (p<0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared to those who survived (p=0.004). Discussion: Although PCT, CRP, and leukocyte values measured at the time of admission were not significantly associated with 1-month mortality in patients with pneumosepsis or pneumonia-related septic shock, the persistent elevation and concurrent increase of these values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.

Planning and implementation of construction projects are difficult processes and are burdened with many risk elements. The budget spread over time, which is developed on the basis of the schedule, presents the expected distribution of costs throughout the duration of the works, which during the implementation of the project is subject to constant changes resulting from time, cost and organizational factors. Managing construction contracts requires managers to be able to analyze on an ongoing basis the variances of production costs - from the values calculated in the offer cost estimate and assumed in the Budgeted Cost of Work Scheduled. The article attempts to analyze the emerging time and cost variances using proprietary C-S and S-C monitoring, based on simple indicators of the EVM method. An example of construction of a multi-family housing development was used to study the variances of planned and incurred costs.

Visible-light photocatalysis, particularly in its application to organic synthesis, has experienced a big renaissance in the past decade. The rational design of new photocatalysts with designed and improved photocatalytic properties, that at the same time circumvents the necessity of using scarce and toxic transition metals, will predictably play a key role in photocatalysis in the next few years. Although free-base porphyrins were identified some years ago as a promising, easily accessible and easily tunable class of organic photoredox catalysts, a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We have prepared a set of known functionalized derivatives of meso-tetraphenyl porphyrin containing different substituents either in one of the meso-positions or at a beta-pyrrole carbon and we have determined their ground- and (singlet) excited-state redox potentials. This survey has led us to conclude that the introduction of a carbonyl group at the beta-pyrrolic position strongly increases the facility of the monoelectronic reduction of the porphyrin both in the ground state and in the singlet excited state. We have also prepared a second set of four previously unknown benzoyl derivatives of meso-tetraphenylporphyrin, and we have confirmed the validity of our conclusions.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Nonparametric assessments of police technical and scale efficiency is challenging because of the stochastic nature of criminal behavior and because of the subjective dependence on multiple decision criteria, which can lead to a more or less efficiency prospect depending on the regulation, necessity, or organizational objective. There is a trade-off between efficiency and effectiveness in many police performance assessments, i.e., efficient departments (producing more clear-ups with a given resource) are crime-specialized or cannot reproduce those good results effectively on more severe or complex occurrences. This study proposes a combined methodology for carrying out efficiency and effectiveness analysis of Police departments. A conditional non-parametric approach, which allows to include crime as an external factor in the analysis, is combined with a non-compensatory ranking based on the PROMETHEE II methodology for the approach illustrated on the multidimensional efficiency and effectiveness comparison of 145 Pernambuco (Brazil)'s police departments. The application results offer compelling perspectives for public administrations concerning the strategic prioritization of units for rewards or interventions.

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4 butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. The PU made with polycarbonate diol polyol (YCD) was the only showing intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis and dynamic mechanical thermal analysis was carried out. It was concluded that the self-healing at 20 °C of YCD was due to non-covalent dynamic exchange interactions among the carbonate groups of the soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to explore the mechanisms behind the vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactivated protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have broad potential for clinical utility, including disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications. In this study, to identify potential modulators of AQPs, we screened 32 natural products by measuring the water and glycerol permeability of mouse erythrocyte membranes using a stopped-flow light scattering method. None of the tested natural compounds substantially affected osmotic water permeability. However, several compounds considerably affected glycerol permeability. Stichoposide C increased the glycerol permeability of mouse erythrocyte membranes, whereas rhizochalin decreased it at nanomolar concentrations. Immunohistochemistry revealed that AQP7 was the main aquaglyceroporin in mouse erythrocyte membranes. We further verified the effects of stichoposide C and rhizochalin on aquaglyceroporins using human AQP3 expressing keratinocyte cells. Stichoposide C, but not stichoposide D, increased AQP3-mediated transepithelial glycerol transport, whereas the peracetyl aglycon of rhizochalin was the most potent inhibitor of glycerol transport among the tested rhizochalin derivatives. Collectively, stichoposide C and the peracetyl aglycon of rhizochalin might function as modulators of AQP3 and AQP7, and suggest the possibility of these natural products as potential drug candidates for aquaglyceroporin modulators

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.