In archaea, the interaction of HerA helicase and NurA nuclease is required for 3' end resection during DNA double-stranded break repair, and its disruption results in unfaithful DNA repair. Interactions transpire by the four conserved domains, including the N-terminal HAS domain (HerA-ATP synthase), which serves as a binding site for the exonuclease NurA. As a HerA hexamer between its two subunits, the conserved C-terminal brace extension functions as an adjacent brace. DBD serves as a location for DNA binding, which causes the DNA strands to be propelled into the HerA pocket to begin unwinding. The putative pore entrance is made up of four helix coils, which provide a suitable charged surface for guiding DNA into the pore. The crystal structure of the complex HerA-NurA allows for the identification of key residues for protein-protein interaction. This allows us to predict that most archaeal HerA orthologs will be able to interact with one another. Archaeal HerA is a homo-hexameric assembly featuring a DNA-binding domain that is conserved. It also features distinctive ATP and NurA binding domains. Following the structure and sequence conservation criteria, we find one HerA ortholog in Pyrobaculum calidifontis and multiple HerA paralogs, but the role of none is established yet.Interestingly, orthologous HerA is part of an Mre11-Rad50 gene neighborhood while paralogous HerA is not, which could be misleading. As a result, it sought to describe the criteria that may be used as a possible fingerprint for identifying orthologous genes, as well as the cloning procedures and tactics that would aid in the confirmation of the HerA helicase in P. calidifontis. Their confirmation is based on PCR cloning and characterization following HerA construct creation.

The efficiency and performance of Proton Exchange Membrane Fuel Cells (PEMFCs) are primarily influenced by ORR electrocatalysts. In recent years, atomically dispersed met-al-nitrogen-carbon (M-N-C) catalysts have gained significant attention due to their high active center density, high atomic utilization, and high activity. These catalysts are now considered the preferred alternative to traditional noble metal electrocatalysts. The unique properties of M-N-C catalysts are anticipated to enhance the energy conversion efficiency and lower the manufac-turing cost of the entire system, thereby facilitating the commercialization and widespread ap-plication of fuel cell technology. This article initially delves into the origin of performance and degradation mechanisms of Fe-N-C catalysts from both experimental and theoretical perspectives. Building on this foundation, the focus shifts to strategies aimed at enhancing the activity and durability of atomically dispersed Fe-N-C catalysts. These strategies encompass the use of bi-metallic atoms, atomic clusters, heteroatoms (B, S, and P), and morphology regulation to optimize catalytic active sites. The article concludes by detailing the current challenges and future pro-spects of atomically dispersed Fe-N-C catalysts.

The utilization of titanium dioxide (TiO2) as a photocatalyst for the treatment of wastewater has attracted significant attention in the environmental field. Herein, we have prepared a NH2-MIL-125-derived TiO2@N-doped C Visible Light Catalyst through an in-situ calcination method. The nitrogen element in the organic connector is released through calcination, simul-taneously doping into the sample, thereby enhancing its spectral response to cover the visible region. The as-prepared TiO2@N-doped C catalyst exhibited preserved cage structure even after calcination, thereby alleviating the optical shielding effect and further augmenting its photo-catalytic performance by increasing the reaction sites between the catalyst and pollutants. The calcination time of the TiO2@N-doped C-450 °C catalyst was optimized to achieve a balance be-tween the TiO2 content and nitrogen doping level, ensuring efficient degradation rates for basic fuchsin (99.7%), Rhodamine B (89.9%), and tetracycline hydrochloride (93%) within 90 minutes.

We report on recent experimental results on β decay into self-conjugate (N=Z) nuclei with mass number 58≤A≤70. Super-allowed β decays from the Jπ=0+ ground state of a Z=N+2 parent nucleus are to the isobaric analogue state, through so-called Fermi transitions, and to Jπ=1+ states, by way of Gamow–Teller (GT) transitions. The operator of the latter decay is a generator of Wigner’s SU(4) algebra and as a consequence GT transitions obey selection rules associated with this symmetry. Since SU(4) is progressively broken with increasing A, mainly as a consequence of the spin–orbit interaction, this symmetry is not relevant for the nuclei considered here. We argue, however, that the pseudo-spin–orbit splitting can be small in nuclei with 58≤A≤70, in which case nuclear states exhibit an approximate pseudo-SU(4) symmetry. To test this conjecture, GT decay strength is calculated with use of a schematic Hamiltonian with pseudo-SU(4) symmetry. Some generic features of the GT β decay due to pseudo-SU(4) symmetry are pointed out. The experimentally observed GT strength indicates a restoration of pseudo-SU(4) symmetry for A=70.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

Japanese pepper (sansho, Zanthoxylum piperitum) contains several types of sanshools belonging to N-alkylamides. Because of long-chain unsaturated fatty acids present in their structure, sanshools are prone to oxidative deterioration, which poses problems in processing. Here, we evaluated the effects of antioxidants from the genus Zanthoxylum in preventing sanshool degradation using accelerated tests. An ethanolic extract of segment membranes of the sansho fruit pericarp was incubated at 70 °C for 7 days with different antioxidants to determine the residual amount of hydroxy-α-sanshool (HαS) in the extract. α-Tocopherol (α-Toc) showed excellent HαS-stabilizing activity at low concentrations. Among phenolic acids, we noted that the HαS-stabilizing activity increased with the number of hydroxy groups per molecule. For example, gallic acid and its derivatives exhibited excellent sanshool-stabilizing activity. Quercetin was found to be a superior HαS stabilizer compared with hesperetin and naringenin. However, the effective concentration was much higher for phenolic compounds than for α-Toc. These substances are believed to play a role in preventing the decomposition of sanshools in the pericarp of sansho. These sanshool stabilizers should be useful in the development of new beverages, foods, cosmetics, and pharmaceuticals that take advantage of the taste and flavor of sansho.

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, yet there is still much to be learnt on how NAGK is regulated in vivo. The use of unicellular green Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provided primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

N-acetyl-L-cysteine (NAC), a sulfhydryl-containing compound, is mainly used as a mucolytic and as an antidote for acetaminophen overdose. Flow injection and sequential injection systems were designed and optimized with the aim of providing precise, accurate and reliable flow methods for NAC determination in pharmaceuticals with very low sample and reagent consumption. Proposed methods are based on a redox reaction wherein NAC reduces a complex of Cu(II) and bathocuproine disulfonate (BCS) to orange [Cu(BCS)2]3– complex, which absorption was measured at λmax = 483 nm. The optimized FIA and SIA configuration yielded a linear calibration curve with correlation coefficients (R2 = 0.9999 and R2 = 0.9996) in the concentration range of 3.0 × 10–7 – 3.0 × 10–5 mol L–1 and analytical frequency of 120 h–1 for the FIA method and 4.0 × 10–7 – 4.0 × 10–5 mol L–1, at sampling rate 60 h–1 for the SIA method. The proposed flow methods were successfully applied for the determination of NAC in pharmaceutical products, as the results showed good agreement with the standard method prescribed by Pharmacopoeia. Recoveries were in the range from 98.4% to 101.9% for the FIA method and from 97.2% to 101.8% for the SIA method.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

The C/N ratio is an extremely important parameter in the composting process, which is directly responsible for the growth of microorganisms. A low C/N ratio contributes to higher emissions of greenhouse gases and odorous substances, such as ammonia (NH3), which is formed by nitrogen mineralization. Due to the highly toxic effects of ammonia, it is a particularly unwanted by-product that can disrupt the composting process because it poisons microorganisms and cause environmental issues. The activity of anammox bacteria, so far analyzed only in wastewater treatment processes, is a particularly efficient method of nitrogen removal, having an advantage over the conventional methods used previously. Our study proofs the presence of anammox bacteria during composting, what gives an opportunity to improve the process and reduce its impact on atmospheric pollution. Despite the aerobic nature of this process, the composted mass of waste presents conditions conducive to the development of these ammonia oxidizing bacteria, as well as other strains of microorganisms cooperating with them. This makes it possible to compost at a low C/N ratio; in addition, there is no need for additional energy supply through aeration, as the processes carried out by anammox bacteria do not require oxygen.

Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1-4, Mnt and Mga) each of which heterodimerizes with Max and largely oppose Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted sets of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members with particular emphasis on the roles played by Max, Mlx and Mxd proteins in suppressing normal and neoplastic growth. These roles are complex due to the temporally- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.

Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation and several other crucial processes during hantavirus infection. In this study we have generated fluorescently tagged N protein constructs derived from Puumalavirus, the dominant hantavirus species in Central, Northern and Eastern Europe. We have comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn. We found a significant spatial correlation of N with vimentin, actin and P-bodies, but not with microtubules. N constructs also co-localized with Gn and Gc, albeit not as strong as the glycoproteins associated with each other. Moreover, we as-sessed oligomerization of N constructs, observing efficient and concentration-dependent multi-merization, with complexes comprising more than 10 individual proteins.

This paper provides a methodology for the production of synthetic images for training neural networks to recognise shapes and objects. There are many scenarios in which it is difficult, expensive and even dangerous to produce a set of images that is satisfactory for the training of a neural network. The development of 3D modelling software has nowadays reached such a level of realism and ease of use that it seemed natural to explore this innovative path and to give an answer regarding the reliability of this method that bases the training of the neural network on synthetic images. The results obtained in the two proposed use cases, that of the recognition of a pictorial style and that of the recognition of migrants at sea, leads us to support the validity of the approach, provided that the work is conducted in a very scrupulous and rigorous manner, exploiting the full potential of the modelling software. The code produced, which automatically generates the transformations necessary for the data augmentation of each image, and the generation of random environmental conditions in the case of Blender and Unity3D software, is available under the GPL licence on GitHub. The results obtained lead us to affirm that through the good practices presented in the article, we have defined a simple, reliable, economic and safe method to feed the training phase of a neural network dedicated to the recognition of objects and features, to be applied to various contexts.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

Vachellia nilotica (L.) Willd. Ex Del. is multipurpose leguminous tree which is common in grass-land and savanna ecosystems in southern and eastern Africa. These ecosystem soils are reported to be acidic and nutrient limited, specifically with regards to nitrogen (N) and phosphorus (P). The presence of this plant in these terrestrial ecosystems improves soil fertility benefiting the sur-rounding vegetation due to its ability fix atmospheric N. This study seeks to understand the mi-crobial symbiosis and physiological adaptations of V. nilotica in these acidic and nutrient defi-cient KZN soils. The soils used for this study were collected from the Ukulinga Grassland Nutri-ent Experiment located at the Ukulinga research farm of the University of KwaZulu-Natal, Pie-termaritzburg, South Africa. Due to long-term soil nutrient addition treatments, these soils of-fered a diverse nutrient variation for better understanding the effects of acidity and nutrient var-iation on microbial symbiosis, plant nutrition and biomass accumulation of V. nilotica. V. nilotica was able to maintain growth by relying on both atmospheric and soil derived N across all treat-ments decreasing carbon (C) growth costs. There was an increased reliance on atmospheric de-rived N of un-nodulated high N treated plants. The plants grown in high N+P soils were able to nodulate with various species from the Mesorhizobium genus which resulted in an increased bio-mass compared to other plants. The results of this study show that V. nilotica can alter N sources to reduce C growth costs. Also, free-living N2 fixing bacteria play an important role under P deficient conditions.

Although sources of seston are much more complicated in lakes compared to marines, the influences of different source on the spatiotemporal variations in seston stoichiometry are still underexplored, especially in large eutrophic floodplain lakes. Here, we investigated the seston stoichiometry across a typical large eutrophic floodplain lake (Lake Taihu) over one year. In addition, we used the n-alkanes proxies for source estimation which are more robust than other elemental indicators (e.g. C: N ratios). Throughout the study, the average value of C: N: P ratio of 143: 19: 1 across Lake Taihu was higher than the classical Redfield ratio, but closed to the synthesized data from other lakes. Generally, seston C: N ratios varied the least across all environments, but C: P and N: P ratios varied widely and shown a significant seasonal pattern with lower ratios of N: P and C: P during senescence seasons and higher ratios in the growing seasons. This seasonal change was mainly associated with the shift from terrestrial-derived seston to algal-derived seston as, the significant lower ratios of terrestrial-derived seston from surrounding agricultural watershed. Spatially, the mean ratios of each site were similar, except relative high values of C: P and N: P ratios in the algal dominated area. Statistically, the predictive power of environmental variables was strongly improved by adding n-alkanes proxies. However, apart from sources indicators, particulate phosphorus (PP) contents also partly explained the spatiotemporal variations in stoichiometric ratios. Nevertheless, the mechanisms behind the dynamics of PP could be totally different and source-specific. This study highlights the priority of using n-alkanes proxies as tools to identify the source of seston which is essential to interpret the spatiotemporal variations in seston stoichiometric ratios among eutrophic floodplain lakes.

Transition-metal-catalyzed amide bond formation from alcohols and amines is an atom-economic and eco-friendly route. Herein, we identified a highly active in situ N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic system for this amide synthesis. Various substrates, including sterically hindered ones, could be directly transformed into the corresponding amides with the catalyst loading as low as 0.25 mol%. In this system, we replaced the p-cymene ligand of the Ru source with a relatively labile cyclooctadiene (cod) ligand so as to more efficiently obtain the corresponding poly-carbene Ru species. Expectedly, the weaker cod ligand could be more easily substituted with multiple mono-NHC ligands. Further HR-MS analyses revealed that two tetra-carbene complexes were probably generated from the in situ catalytic system.

In the present study, the performance of a 70 L photobioreactor, operating outdoors, was investigated using a purple bacterial strain as Rhodopseudomonas sp. S16-VOGS3 for producing poly-3-hydroxybutyrate (PHB). The novel photobioreactor was equipped with 5L-shaped rows; the bottom of every row was placed in a stainless-steel tank containing water with controlled temperature. The photofermentation trials were carried out under fed-batch mode and under a semi-continuous regimen using lactic acid as carbon source. The effect of the irradiance and the C/N ratio on the PHB accumulation was investigated, in order to evaluate the optimal bacterial growth. The results showed the feasibility of the prototype photobioreactor for the production of PHB by Rhodopseudomonas sp. S16-VOGS3 under the natural light/dark cycle. During the fed-batch growth (144 h long), the cumulative PHB increased quickly reaching the maximum value of 377 mg/L and decreased to 255 mg/L during the semi-continuous regimen (336 h long).

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

The endo- and exo-N-heterocyclic carbene precursors based on camphor were prepared diastereoselectively in five synthetic steps starting from (1S)-(+)-ketopinic acid. The obtained N-heterocyclic carbene precursors were investigated in an asymmetric benzoin reaction. All new compounds were fully characterized and the absolute configurations were determined by X-ray diffraction and NOESY measurements.

A two-step, one-pot synthesis of 3-substituted 1H-dibenzo[e,g]indazoles in good to high yields via a LiOtBu-promoted intramolecular cyclization of 2’-alkynyl-biaryl-2-aldehyde N-tosylhydrazones, formed in situ by the reactions of 2’-alkynyl-biaryl-2-aldehydes with p-methylbenzenesulfonohydrazide was developed. Two kinds of hydrogen bonds forming in several products were observed in DMSO-d6 solution in 1H NMR spectroscopic data, which were assigned to the formation of solvated products and dimers of products, supported by the studies of density functional theory (DFT).

Weak contact metric structures on a smooth manifold, introduced by V. Rovenski and R. Wolak in 2022, have provided new insight into the theory of classical structures. In this paper, we define new structures of this kind (called weak nearly Sasakian and weak nearly cosymplectic and nearly K\"{a}hlerian structures) and study their geometry. We introduce weak nearly K\"{a}hlerian manifolds (generalizing nearly K\"{a}hlerian manifolds) and characterize weak nearly Sasakian and weak nearly cosymplectic hypersurfaces in such Riemannian manifolds.

Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, effects of different types of antioxidants on stability and bioactivities of curcumin were analyzed. High concentrations (>4mM) of the thiol antioxidants including N-acetylcysteine (NAC), glutathione (GSH) and β-mercaptoethanol accelerated decomposition of curcumin and other curcuminoids; Submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin regardless of their concentration. Cellular levels and bioactivities of curcumin including cytotoxicity and induction of heme oxygenase-1 were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with reduced thiol group could directly interact with α, β-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

Emerging pollutants as pharmaceuticals have been focusing international attention for few decades. Ciprofloxacin (CIP) is a common drug widely found in effluents from hospitals, industrial and different wastewater treatment plants, as well as rivers. In this work, the lab-scale 3D-BER system was established, and more than 90% of the antibiotic CIP removal from the Low C/N wastewater. Best results were obtained with current intensity, and different C/N ratio significantly improve the removal of CIP and nitrates, when the ideal conditions were; C/N = 1.5-3.5, pH =7.0-7.5, and I = 60 mA. The highest removal efficiency of CIP = 94.20 %, NO3--N= 95.53 % and total nitrogen (TN) = 84.27 %, respectively. In this novel system, the autotrophic-heterotrophic denitrifying bacteria played vital role for the removal of CIP and enhanced denitrification process. Thus, autotrophic denitrifying bacteria uses CO2 and H2 as carbon sources to reduce nitrates to N2. This system has the assortment and prosperous community revealed at the current intensity of 60 mA, and the analysis of bacterial community structure in effluent samples fluctuates under different condition of C/N ratios. According to the results of LC-MS/MS analysis, the intermediate products were proposed after efficient biodegradation of CIP. Microbial community on biodegrading was mostly found at phylum, and class level was dominantly responsible for the NO3--N and biodegradation of CIP. This work can provide some new insights towards the biodegradation of CIP and the efficient removal of nitrates from low C/N wastewater treatment by the novel 3D-BER system.

Causative agent of the viral pneumonia outbreak in the World identified as SARS-CoV2 leads to a severe respiratory illness like SARS and MERS. The pathogen spreading has turned into a pandemic dissemination and increased the mortality rate. Therefore, useful information is urgently necessary for effective control of the disease. Our study shows the existence of unvarying sequence with no mutation, including ORF1ab regions in 134 high-quality filtered genome sequences of SARS-CoV2 downloaded from the GISAID database. We have detected this sequence stability by using MAUVE analysis and pairwise alignment with Global Needleman Wunsch algorithm for each two different sequences, reciprocally. They also confirmed all these results were also with the Clustal W analysis. The first 6500 bp including ORF1ab region is an unvarying sequence. According to the highest TM-score of predicted protein structure analysis, the results showed it is very similar to spike protein of feline infectious peritonitis virus strain UU4 (PDB 6JX7) depending on amino acid sequences encoded by this unvarying region, and N-acetyl-D-glucosamine is the ligand of this protein. These results have confirmed that N-acetyl-D-glucosamine could play an important role in controlling of SARS-CoV-2. Also, our molecular docking analysis data supports a strong protein-ligand interaction of N-acetyl-D-glucosamine with spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS CoV-2. Therefore, binding of N-acetyl-D-glucosamine to these proteins could inhibit SARS CoV-2’s replication. In the present work, we have suggested providing a repurposing compound for further in vitro and in vivo studies and new insights for ongoing clinical treatments as a new strategy to control of SARS-CoV-2 infections.

The “NWCSAF High Resolution Winds (NWC/GEO-HRW)” software is developed by the EUMETSAT’s “Satellite Application Facility on support to Nowcasting and very short range forecasting (NWCSAF)”, inside its stand-alone software package for calculation of meteorological products with geostationary satellite data (NWC/GEO). The whole NWC/GEO software package can be obtained after registration at the NWCSAF Helpdesk, www.nwcsaf.org. It is easy to get, install and use. The code is easy to read and fully documented. And in the NWCSAF Helpdesk, users find support and help for its use. “NWCSAF High Resolution Winds” provides a detailed calculation of Atmospheric Motion Vectors (AMVs) and Trajectories, locally and in near real time, using as input NWP model data and geostationary satellite image data. The latest version of the software, v2018, is able to process MSG, Himawari-8/9, GOES-N and GOES-R satellite series images, so that AMVs and Trajectories can be calculated all throughout the planet Earth with the same algorithm and quality. In the “2014 and 2018 AMV Intercomparison Studies”, “NWCSAF High Resolution Winds” has shown to be one of the two best AMV algorithms for both MSG and Himawari-8/9 satellites. And the “Coordination Group for Meteorological Satellites (CGMS)” has recognized in its “2012 Meeting Report”: 1. “NWCSAF High Resolution Winds” fulfills the requirements to be a portable stand-alone AMV calculation software due to its easy installation and usability. 2. It has been successfully adapted by some CGMS members and serves as an important tool for development. It is modular, well documented, and well suited as stand-alone AMV software. 3. Although alternatives exist as portable stand-alone AMV calculation software, they are not as advanced in terms of documentation and do not have an existing Helpdesk. Considering this, a full description and validation of the “NWCSAF/High Resolution Winds” is shown here for the first time in a peer-reviewed paper. The procedure to obtain the software for operational meteorology and research is also explained.

Generating a range-wide population status of the diamondback terrapin (Malaclemys terrapin spp.) is challenging due to a combination of species ecology and behavior, and limitations associated with traditional sampling methods. Visual counting of emergent heads offers an efficient, non-invasive and promising method for generating abundance estimates of terrapin populations across broader spatial scales and can be used to explain spatial variation in population size. We conducted repeated visual head count surveys at 38 predetermined sites along the shoreline of Wellfleet Bay in Wellfleet, Massachusetts. We analyzed the count data using a hierarchical modeling framework designed specifically to analyze repeated count data: the so-called N-mixture model. This approach allows for simultaneous modeling of imperfect detection to generate estimates of true terrapin abundance. We found detection probability was lowest when skies were overcast and when wind speed was highest. Site specific abundance varied but we found that abundance estimates were, on average, higher in unexposed sites compared to exposed sites. We demonstrate the utility of pairing visual head counts and N-mixture models as an efficient method for estimating terrapin abundance and show how the approach can be used to identifying environmental factors that influence detectability and distribution.

Inspired by amazing result obtained by Semay [1], this study revisits generalised Kepler's third law of an n-body system from the perspective of dimension analysis. To be compatible with Semay's quantum n-body result, this letter reports a conjecture which had not be included in author's early publication [2] but formulated in the author's research memo. The new conjecture for quantum N-body system is proposed as follows: Tq|Eq|^3/2 = πG/√2[(Σ^N_i=1 Σ^N_j=i+1 m_im_j)³/(Σ^N_k=1 m_k)]^1/2. This formulae is, of course, consistent with the Kepler's third law of 2-body system, and exact same as Semay's quantum result for identical bodies.

The enhancement of health-beneficial omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart and kidney of prime lambs. Lambs grazing cocksfoot only had the highest 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100g and 55.2 mg/100 g, respectively). Supplementation of pellets with or without oil infusion to grazing lambs decreased the ALA and n-3 LC-PUFA contents and increased n-6/n-3 ratio in Longissimus dorsi muscle. The fatty acid content in internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA which may consequently enhance the omega-3 intake of Australian lamb consumers.

Introduction The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies, as well as to evaluate published data on the addition of some of HMOs to infant formula. Method PubMed was searched from inception to April 2018 Results The presence of HMOs is a dynamic process, determined by many factors such as duration of lactation, environmental and genetic factors. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. Only a few of the many HMOs can be made industrially, and are added to infant formula. They have been shown to be safe and well tolerated, including normal growth and a trend towards health benefit. Conclusions HMOs are one of the major differences between cow’s milk and human milk , and evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk.

This paper presents a methodology to detect the erosion and progradation effects in the Atrato river delta, located in the Gulf of Urabá in Colombia using SAR (Synthetic Aperture Radar) data. Other authors have studied this area by using optical images, encountering difficulties given the persistent presence of clouds in this region. SAR imagery is rescaled, despeckled, composed, classified, registered and processed to obtain a heatmap that shows the overall changes during eight years (2016–2023) in one single image. Since this technology uses microwave active signals, the presence of clouds and other environmental phenomena was not a problem, and all the images from the selected dates could be processed and analyzed. Also, detection of the dynamic processes was obtained for every period considered in this study with respect to the previous one in time, calculating areas and detecting the regions subject to the erosion and progradation processes. The multitemporal analysis performed found that the newly created mouth is the most active area for these processes, coinciding with other studies. A comparison of these findings with the Oceanic Niño Index (ONI) showed a relative delayed coupling to the erosion process and a coupling of progradation with dry and wet seasons.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

Let  β= (((24!)!)!)!, and let {${\mathcal P}_{n^2+1}$} denote the set of all primes of the form {$n^2+1$}. Let ${\mathcal M}$ denote the set of all positive multiples of elements of the set {${\mathcal P}_{n^2+1} \cap (\beta,\infty)$}. The set {${\mathcal X}=\{0,\ldots,\beta\} \cup {\mathcal M}$} satisfies the following conditions: (1) ${\rm card}({\mathcal X})$ is greater than a huge positive integer and it is conjectured that ${\mathcal X}$ is infinite, (2)} we do not know any algorithm deciding the finiteness of ${\mathcal X}$, (3)~a~known and short algorithm for every {$n \in N$} decides whether or not {$n \in {\mathcal X}$}, (4) a known and short algorithm returns an integer~$n$ such that ${\mathcal X}$ is infinite if and only if ${\mathcal X}$ contains an element greater than $n$. The following problem is open: {\em simply define a set {${\mathcal X} \subseteq N$} such that ${\mathcal X}$ satisfies conditions (1)-(4), and \underline{we do not know any representation of~~${\mathcal X}$~~as a finite union of sets whose definitions are simpler than} \underline{the definition of ${\mathcal X}$}} {\tt (5)}. Let {$f(1)=2$}, {$f(2)=4$}, and let {$f(n+1)=f(n)!$} for every integer {$n \geqslant 2$}. For a positive integer $n$, let {$\Psi_n$} denote the following statement: {\em if a system of equations ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: i,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers \mbox{$x_1,\ldots,x_n$}, then each such solution \mbox{$(x_1,\ldots,x_n)$} satisfies {$x_1,\ldots,x_n \leqslant f(n)$}.} We prove that for every statement $\Psi_n$ the bound {$f(n)$} cannot be decreased. The author's guess is that the statements {$\Psi_1,\ldots,\Psi_9$} are true. We prove that the statement $\Psi_9$ implies that the set ${\mathcal X}$ of all {non-negative} integers $k$ whose number of digits belongs to {${\mathcal P}_{n^2+1}$} satisfies conditions {\tt (1)-(5)}.

This study evaluates the viability of n-octanol as an alternative fuel in a direct-injection diesel engine, aiming to enhance sustainability and efficiency. Experiments employed varying blends of n-octanol (10%, 30%, and 50% by volume) with pure diesel, analyzing impacts on engine performance and emissions. The methodology involved testing each blend in a single-cylinder engine, measuring engine performance parameters such as brake torque and brake power under full load conditions across an engine speed range from 1400 to 2500 rpm. Comparative assessments of performance and emission characteristics at a constant engine speed of 1700 rpm were also conducted with varying loads. Results indicated that while n-octanol blends consistently improved brake thermal efficiency, they also increased brake specific fuel consumption due to the lower energy content of n-octanol. Consequently, while all n-octanol blends reduced nitrogen oxides (NOx) emissions compared to pure diesel, they also significantly decreased carbon monoxide, hydrocarbons, and smoke opacity, presenting a comprehensive reduction in harmful emissions. However, the benefits came with nuanced trade-offs: notably, higher concentrations of n-octanol (especially the 50% blend) led to a relative increase in NOx emissions as the octanol ratio increased. The study concludes that n-octanol significantly improves engine efficiency and reduces diesel dependence, but optimizing the blend ratio is crucial to balance performance improvements with comprehensive emission reductions.

Data on Stark broadening parameters, spectral line widths and shifts, for 15 multiplets of N VI, which spectral lines are broadened by collisions with electrons, protons, alpha particles (He III) and B III, B IV, B V and B VI ions, are presented. They have been calculated, using the semiclassical perturbation theory, for temperatures from 50,000 K to 2,000,000 K, and perturber densities from 1016 cm−3 up to 1024 cm−3. These data are particularly of interest for the analysis and modelling of atmospheres of hot and dense stars, as e.g. white dwarfs, and for investigation of their spectra, but also for analyis ad modelling of laser driven plasma in proton-boron fusion research.

The draconian regulation required by the inherent instability of cognitive phenomena -- gene expression, immune function, cancer suppression, wound healing, animal consciousness, machine intelligence, network stabilization, institutional cognition, and their many and varied composites -- can be viewed through the lens of the asymptotic limit theorems of both information and control theories. Here, we explore the dynamics and sometimes highly punctuated failures of the regulation of cognition under increasing `noise'. The approach parallels, and indeed generalizes, the Data Rate Theorem of control theory, extending the theorem's requirement of a minimum channel capacity necessary for stabilization of an inherently unstable system. Various models are explored across different basic underlying probability distributions characteristic of the system under study, and across different hierarchical scales, finding the addition of adaptive -- learned -- regulation greatly extends the reach of innate -- e.g., AI-driven or otherwise pre-programmed -- regulation. This work points toward the construction of new statistical tools for the analysis of observational and empirical data across a wide spectrum of inherent pathologies and adversarial challenges afflicting a wide variety of cognitive processes.

The forest regeneration phase in Sweden commonly involves mechanical soil preparation followed by planting of Scots pine or Norway spruce seedlings. The prepared soil offers planting positions with different properties, including decreased damage by pine weevil (Hylobius abietis L.). Nitrogen fertilization can be applied at the time of planting to aid establishment of the seedlings. In this study we compared the effect of organic nitrogen-fertilization for different planting positions, and seedling sizes on early survival and growth of Scots pine and Norway spruce seedlings. The main planting positions were capped mound, hinge, and mineral soil. Seedlings planted close to organic material were categorized as “low quality positions”, since proximity to organic material increase pine weevil attraction. Higher mortality rates related to pine weevil damage were recorded for seedlings planted in the low-quality positions, regardless of seedling size or N-fertilization. Pine weevil attack rates increased with increasing seedling size. Growth was in general lowest in mineral soil positions. The effect of organic N-fertilization on growth was positive for spruce regardless of planting positions and seedling size, while depending on planting position and seedling size for pine, indicating that effects of organic N-fertilization depend on seedling species, -size and planting position.

Support effect is an important issue in heterogeneous catalysis while the explicit role of a catalytic support is often unclear for catalytic reactions. A systematic density functional theory computational study is reported in this paper to elucidate the effect of a model boron nitride (BN) support on the first N-H bond activation step of NH3 on Run (n =1, 2, 3) metal clusters. Geometry optimizations and energy calculations were carried out using density functional theory (DFT) calculation for intermediates and transition state from the starting materials undergoing the N-H activation process. The primary findings are summarized as follows. The involvement of the model BN support does not significantly alter the equilibrium structure of intermediates and transition state in the most favorable pathway (MFP). Moreover, the involvement of BN support decreases the free energy of activation, ΔG≠, thus improving the reaction rate constant. This improvement is more obvious at high temperatures like 673 K than low temperatures like 298 K. The BN support effect leading to the ΔG≠ decrease is most significant for the single Ru atom case among all three cases studied. Finally, the involvement of model BN may change the spin transition behavior of the reaction system during the N-H bond activation process. All these findings provide a deeper insight into the support effect on the N-H bond activation of NH3 for supported Ru catalyst in particular and for supported transition metal catalysts in general.

High-performance properties of interpenetration polymer network (IPN) hydrogels, based on physically crosslinked chitosan (CS) and chemically crosslinked poly(N-isopropylacrylamide) (PNiPAM), have been successfully developed. The IPN of CS/PNiPAM is proposed to overcome the limited mechanical properties of the single CS network. In this study, the viscoelastic behaviors of prepared materials in both solution and gel states have been extensively examined, considering the UV exposure time and crosslinker concentration as key factors. The effect of these factors on gel formation, hydrogel structures, thermal stabilities of networks, and HeLa cell adhesion were studied sequentially. The sol-gel transition was effectively demonstrated through the scaling law, which agrees well with Winter and Chambon's theory. By subjecting the CS hydrogel to the process operation in an ethanol solution, its properties can be significantly enhanced with increased crosslinker concentration, including the shear modulus, crosslinking degree, gel strength, and thermal stability in its swollen state. The IPN samples exhibit a smooth and dense surface with irregular pores, allowing for much water absorption. The HeLa cells were adhered to and killed using the CS surface cationic derivative, then released through hydrolysis by utilizing the hydrophilic/hydrophobic switchable property or thermo-reversible gelation of the PNiPAM network. The results demonstrated that IPN is a highly attractive candidate for anti-fouling materials.

This article introduces ten similarity measures that utilize cosine and cotangent functions to compare (m,n)-rung orthopair fuzzy sets, this a super class of q-rung orthopair fuzzy sets. Further, we applied our established weighted similarity measures to medical diagnosis, pattern recognition,and building material problems and also presented the comparison between established measures with the existing cosine and cotangent measures of q-rung orthopair, pythagorean and intuitionistic fuzzy sets. Lastly, we considered a numerical example that demonstrates the effective and scientific application of these similarity measures in plant leaf disease classification. Furthermore, we present graphical interpretations to demonstrate the effectiveness of our established measures.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

This research is focused on two key areas. The first is mapping the 2022 flood in the Red River of the North near Grafton, North Dakota, US, and the second is evaluating the scour potential of the Grafton Bridge. Local scour of bridge piers can cause hydraulic structures such as bridge piers and abutments to fail during floods, making it a crucial area of investigation. To collect bathymetry and discharge data during low and high flow conditions, including a flood event with a 16.5-year return period in 2022, an Autonomous Surface Vehicle (ASV) incorporated with LiDAR DEM (Digital Elevation Model) data obtained from the US Geological Survey (USGS) National Map was used. Flood mapping and evaluation of local scour around the bridge pier were conducted using the HEC-RAS 6.0.0 software, which utilizes the Colorado State University method as a default equation. This research demonstrates the potential of ASVs in collecting critical data and LiDAR DEM data is an efficient method for flood mapping and determining scour potential, as it integrates bathymetry, flow velocity, and flood prediction.

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects. An additional experiment was carried out in eight male C57BL/6J mice fed a Western-type diet for twelve weeks. The strategy for glycemic control in the T2D patients significantly improved the HbA1c concentrations without producing changes in the estimated glomerular filtration rate. However, the plasma TMAO and γBB concentrations were significantly increased following the glycemic control in T2D patients. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in mice. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. The contribution of antidiabetic drugs to gut microbiota composition could explain TMAO elevations in treated T2D subjects.

Despite the rising interest in smart city initiatives worldwide, governmental theories along with the managerial perspectives of city planning are a great lack in the literature. It is definitely understandable that the adoption of configurational pathways towards the ‘smart’ ‘governance’ models is required as key factor and smartness’ facilitator in modern cities. In this manuscript, we display an exhaustive analysis on the importance of the n-Helix models along with a benchmarking critical approach through selected European case-studies. The study, through the literature review, revealed the lack of exhaustive analyses for the methodological investigation, identification and adoption of the most appropriate governance model and collaborative approaches per project and collaborative approaches and create modular frameworks to address efficiently the continuous urban challenges, such as the rapid urbanization or the climate change.

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites (e.g., exosites, ectosites) through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches such as proteomics and N-terminomics to identify new MMP substrates and achieve a better understanding of the roles of these proteases in diseases.

This study numerically analyzed the effect of composition and temperature and oxygen concentration changes on the selfignition characteristics of n-heptane/methane blended fuels in order to cope with development of alternative fuels and international environmental regulations. CHEMKIN-PRO is used as the analysis program and the LLNL model is used as the reaction model. The numerical results revealed that on autoignition and ignition delay time were sensitive to changes in fuel composition and oxygen concentration. As the methane ratio increases, OH radicals causing ignition are delayed in generation and the concentration is lowered, thus longer the ignition timing. The oxygen concentration in the mixed fuels are changed to simulate the exhaust gas recirculation and a numerical analysis in then performed. As the oxygen concentration decreases, the ignition delay time longer because the nitrogen gas acts as a thermal load in the combustion chamber.

In plant cells the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment. However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage. Given the high sequence similarity between the PSIs domains, we sought to depict the differences in terms of post-translational modifications. In fact, one feature that draws our attention is that one is N-glycosylated and the other one is not. Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole. This is also true when the PSI domain is analyzed in the context of the full-length cardosin. Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.

N-acyl hydrazone (NAH) has been remarked as a promising scaffold in drug design, given its versatility, ease of synthesis, and appealing biological activities (i.e., antimicrobial, antitumoral, analgesic, and anti-inflammatory properties). In the global context of increasing resistance of pathogenic bacteria to antibiotics, NAHs represent potential solutions for developing improved treatment alternatives. Thus, this study presents 6 new derivatives of (EZ)-N'-benzylidene-(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanohydrazide that were obtained through a microwave-assisted synthesis method. In more detail, we have joined two pharmacophore fragments in a single molecule, represented by an NSAID-type carprofen structure and a hydrazone-type structure, obtaining a new series of NSAID-N-acyl hydrazone derivatives that were further characterized spectrally using FT-IR, NMR, and HRMS investigations. Moreover, the compounds have been evaluated for their tuberculostatic activity, testing their effects on four M. tuberculosis strains (two of them susceptible to rifampicin (RIF) and isoniazid (INH), one susceptible to RIF and resistant to INH and one resistant to both RIF and INH). The results of our research highlight the potential of the prepared compounds in fighting against antibiotic-resistant M. tuberculosis strains.

The effect of neutron irradiation of Si-Ge/Si film structures obtained by gas-phase epitaxy on the processes of charge carrier generation and the magnitude of the dark short-circuit current and open-circuit voltage caused by it is studied, it is shown that their magnitude practically does not change with time. The results obtained indicate that all types of structural defects, both associated with dopant impurities and radiation exposure, contribute to the generation of charge carriers in heated silicon structures with the participation of deep energy levels, which indicates the applicability of neutron processing of silicon materials to create thermal energy converters, operating at high temperatures.

The rationalization and modeling of an electric discharge in a fluid require the knowledge of electron swarm parameters. In this work, transport coefficients of alcohols, including methanol, ethanol, propanol, and butanol are reported. The electron energy distribution function, mean energy, reduced mobility, and diffusion coefficient, are calculated using the two-term expansion of the electron Boltzmann equation in the frame of BOLSIG+ and the Monte Carlo collision code METHES. For such, experimental and theoretical values of the electron-alcohol collision cross-section, covering a range of electron impact energy from 1 eV to 1000 eV, are employed. A temperature of 300K, reduced fields E/N between $1-10^4$ Td (1Td = $10^{-21}~\rm Vm^2$), and Plasma density of $10^{19}~\rm m^{-3}$ were used in simulations. The calculated coefficients are compared with data available from previous studies.

Duchenne muscular dystrophy (DMD), the severest form of muscular dystrophy, is characterized by progressive muscle weakness with fatal outcome most often before the fourth decade of life. Despite recent addition of molecular treatments, DMD remains a disease without a cure, and the need persists for the development of supportive therapies aimed to help improve patients’ quality of life. This review focusses on the therapeutical potential of amino acid and derivative supplements, summarizing results obtained in preclinical studies in the murine disease model. Several promising compounds have come forward, with L-arginine, N-acetylcysteine and taurine featuring among the most intensively investigated. Beneficial effects include improved muscle function and reduced muscle fiber necrosis and reduced inflammatory and oxidative damage to muscle tissues, however mild side effects have also surfaced. In order to identify amino acid formulae that are safe and of true benefit to DMD patients, more explorative, placebo-controlled and long-term clinical trials need to be conducted, documenting therapeutic outcomes.

This paper proposes an AI-based approach to overcome the limitations of the SHM system in measuring global stress with limited sensors. Feature elements are selected based on correlation analysis among finite elements and used as stress-measured points. An ANN is used to establish the solution relationship between the feature and correlation elements. The proposed method is applied to the connector structure of an offshore platform, and an optimal ANN is established to optimize accuracy by considering factors like the number of sensors, neural network framework, and convergence criteria. The accuracy of the ANN is verified through a real-scale model test, demonstrating 93.6% accuracy. This technology represents a significant advancement, enhancing the practicality of the structural health monitoring (SHM) system from “point monitoring" to “field monitoring".

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

Plazomicin is a recently U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2′-N-acetyltransferase type Ia [AAC(2′)-Ia], which reduces the antibiotic’s potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit acetylation of numerous aminoglycosides catalyzed by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib]. In particular, Ag1+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6′)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2′)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2′)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

The Betz limit sets a theoretical upper limit for the power production by turbines expressed as a maximum power coefficient of 16/27. Betz’s theory is accurate and it is based on the calculation of kinetic energy.

The bioactivities of collagen-hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen-hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics were evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceuticals data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameters were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen-hydrolysates or sulfated glucosamines. Collagen-hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen-fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen-hydrolysates, sulfated glycans (i.e. sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Different contact materials along with optimization of the deposition techniques expand the possibilities to obtain high performance room temperature CdTe-based X/γ-ray detectors. The heterostructures with ohmic (MoOx) and Schottky (MoOx, TiOx, TiN, and In) contacts, created by DC reactive magnetron sputtering and vacuum thermal evaporation, as well as In/CdTe/Au diodes with a p-n junction, formed by laser-induced doping, were developed and investigated. Depending on the pre-treatment of the surface of semi-insulating p-CdTe crystals, deposition of a MoOx film formed an ohmic or Schottky contact. Based on the calculations and IV characteristics of the fabricated Mo-MoOx/р-CdTe/MoOx-Mo, In/CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo Schottky-diode detectors, the current transport processes were described in the models of the carrier generation-recombination within the space-charge region (SCR) at low bias voltages, and space-charge limited current at higher voltages, respectively. The energies of generation–recombination centers, density of trapping centers, and carrier lifetimes were determined. A sharp increase in the reverse current in the Mo-MoOx/р-CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo heterostructures at high bias was discussed in frames of the Poole–Frenkel emission model. Nanosecond laser irradiation of the In electrode, pre-deposited on the p-CdTe crystals, resulted in an increase in the voltage range, corresponding to the carrier generation-recombination in the SCR, in the IV characteristics of the In/CdTe/Au diodes. Such In/CdTe/Au p-n junction diodes demonstrated high energy resolutions (7%@59.5 keV, 4%@122 keV, and 1.6%@662 keV).

The use of swine manure as a source of plant nutrients is one alternative to synthetic fertilizers. However, conventional manure application with >90% water and a low C:N ratio results in soil C loss to the atmosphere. Our hypothesis was to use biochar as a manure nutrient stabilizer that would slowly release nutrients to plants upon biochar-swine manure mixture application to soil. The objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and plant-available macro and micronutrients in greenhouse-cultivated corn (Zea mays L.) and soybean (Glycine max (L.) Merr.). Neutral pH red oak (RO), highly alkaline autothermal corn stover (HAP), and mild acidic Fe-treated autothermal corn stover (HAPE) biomass were pyrolyzed to prepare biochars. Each biochar was surface-applied to swine manure at a 1:4 (biochar wt/manure wt) ratio to generate mixtures of manure and respective biochars (MRO, MHAP, and MHAPE). Conventional manure (M) control and manure-biochar mixtures were then applied to the soil at a recommended rate. Corn and soybean were grown under these controls and treatments (S, M, MRO, MHAP, and MHAPE) to evaluate the manure-biochar impact on soil quality, plant biomass yield, and nutrient uptake. Soil OM significantly (<0.05) increased in all manure-biochar treatments; however, no change in soil pH or N was observed under any treatment. No difference in soil ammonium between treatments was identified. There was a significant decrease in soil M3-P and soil NO₃^- for all manure-biochar treatments compared to the conventional M. However, the plant biomass nutrient concentrations were not significantly different from control manure. Moreover, an increasing trend of N and decreasing trend of P in the plant under all biochar-manure treatments than the controls were noted. This observation suggests that the presence of biochar is capable of influencing the soil N and P in such a way as not to lose those nutrients at the early growth stages of the plant. In general, no statistical difference in corn or soybean biomass yield and plant nutrient uptake for N, P, and K was observed. Interestingly, manure-biochar application to soil significantly diluted the M3-extractable soil Cu and Zn concentrations. The results attribute that manure-biochar has the potential to be a better soil amendment than conventional manure application to the soil.

Plants are affected by soil environments to the same extent they affect soil functioning through interactions between environmental and genetic factors. Here, five plant species (broad bean, pea, cabbage, fennel, and olive) grown under controlled pot conditions were tested for their ability to differently stimulate the degradation of standard litter. Litter, soil C and N contents and soil microbial abundance were measured. The architecture and morphological traits of roots systems were also evaluated by using specific open-source software (SmartRoot). Soil chemical and microbiological characteristics were significantly influenced by the plant species. Variations in soil C/N dynamics were correlated with the diversity of root traits among species. Early-stage decomposition of the standard litter changed on the basis of the plant species. The results indicated that key soil processes are governed by interactions between plant roots, soil C and N, and the microbial metabolism that stimulate decomposition reactions. This, in turn, can have marked effects on soil chemical and microbiological fertility, both fundamental for sustaining crops, and can promote the development of new approaches for optimizing soil C and N cycling, managing nutrient transport, and sustaining and improving net primary production.

Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed recombinant SARS-CoV-2 Spike protein secreted from BTI-Tn-5B1-4 cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired MS/MS spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of Spike proteins according to Cryo-EM and homolog-modeled structures, and available antibodies that bind to SARS-CoV-1. The results showed that all 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose type of N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the Spike receptor binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV-1, and 985 to 1034 of SARS-CoV-2 Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.

A platinum (II) complex stabilized by a pyridine and a N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the NHC Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase AFM microscopy. The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behaviour was quantified from the different experiments due to contour length variations. At 24h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.

The aim of the study was to determine the possibility of suppression of the prostaglandin synthesis by new derivatives of N-phenylanthranilic acids; they inhibit the activity of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme using the method of a flexible molecular docking. For the docking studies the crystallographic structural models with high resolution from Protein Data Bank were used: mPGES-1 in the complex with glutathione (pdb code 4AL0). A flexible molecular docking was carried out using the Molecular Operating Environment (MOE) software package. According to the results of the docking studies four scoring functions were calculated (Affinity dG Scoring, Alpha HB Scoring, London dG Scoring, GBVI/WSA dG Scoring). The values of the scoring functions calculated indicate the thermodynamic probability and energy favorability of forming complexes between molecules of the substances under research and the specified receptor, in which arrangement of ligands in the active site of the receptor and residues of amino acids of side chains are of similar geometry and types of binding of the known inhibitors of mPGES-1 determined on the basis of the crystallographic studies.

In this paper we introduce the hypo-q-norms on a Cartesian product of algebras of bounded linear operators on Hilbert spaces. A representation of these norms in terms of inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar reverses of Cauchy-Buniakowski-Schwarz inequality are also given. Several bounds for the norms δ_p, ϑ_p and the real norms η_r,p and θ_r,p are provided as well.

In this study we introduce the new classes $\mathcal{M}_{\alpha}(\sin)$ and $\mathcal{M}_{\alpha}(\cos)$ of $\alpha$-convex functions associated with sine and cosine functions. Also, we obtain the initial coefficient bounds for the first five coefficients of the functions that belong to these classes. Further, we determine the upper bound of Zalcman functional for the class $\mathcal{M}_{\alpha}(\cos)$ for the case $n=3$, showing that the Zalcman conjecture holds for this value. Moreover, the problem of the Fekete-Szeg\H{o} functional estimate for these classes is studied.

A hydrophilic silica-based stationary phase with surface bound N-acetylglucosamine (GlcNAc-silica) was prepared in house and characterized physically via Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) and chromatographically over a wide range of mobile phase compositions. While both FTIR and TGA confirmed the attachment of the GlcNAc ligands to the silica surface, the chromatographic evaluation of the GlcNAc-silica with polar and slightly polar standard solutes (e.g., sugars, nucleic acid fragments, phenolic and benzoic acid derivatives) yielded the typical hydrophilic interaction liquid chromatography (HILIC) behaviors in the sense that retention increased with increased solute’s polarity and the organic content (i.e., acetonitrile) of the hydro-organic mobile phase (i.e., ACN-rich mobile phase). Sugars derivatized with 1-naphthylamine (1-NA) and 2-aminoanthrcene (2-AA) such as xylose, glucose and short chains maltooligosaccharides constituted the most polar species for HILIC retention evaluation, and in addition the maltooligosaccharides offered a polar homologous series for gauging the hydrophilicity of the GlcNAc-silica in analogy with alkylbenzene homologous series and other nonpolar homologous for evaluating the hydrophobicity of non-polar stationary phases. On the other hand, the benzoic acid and phenolic acid derivatives were the probe solutes for evaluating the HILIC retention dependence of ionizable solutes on the pH of the mobile phase. Similarly, the nucleobase and nucleoside weak basic solutes as well as some typical cyclic nucleotide acidic solutes allowed the examination of the dependence of solute retention on the pH of the mobile as well as the polarity of the species.

Due to the low content, few studies are focused on the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (syn. Lamiophlomis rotata (Benth.) Kudô. This plant has been used to treat rheumatic arthritis and grasserie in China. However, such EOs may have important pharmacological activities such as anti-cancer. To identify the chemical markers (CM) in the EOs and evaluate their antioxidant activities (AAs), we firstly conduct a thoroughly investigation on their chemicals and AAs, to the best of our knowledge. Light yellow EOs with fresh and elegant smell are obtained by hydro-distillation with average yield 0.11% (volume mL/weight g). The crystals are separated from the EOs through cryoprecipitation, respectively. A total of 81 components are qualified and quantified in the EOs, crystals and EOs removed crystals, in which 44 ones are first reported. As for content, the main compounds are long-chain fatty acids (FAs) and their esters. The most abundant one n-hexadecanoic acid (palmitic acid, PA) accounting for 43.15-54.8%, 58.49-64.57% and 15.9-41.1%, in the EOs, crystals and EOs removed crystals, respectively. Seven compounds including PA, tetradecanoic acid, linoleic acid, oleic acid, methyl hexadecanoate, hexahydrofarnesyl acetone and phytol can be chosen a the CMs in these EOs. The AAs are evaluated through in vitro assays. PA presents pro-oxidant activities in a concentration dependence manner. Usually, the EOs removed crystals demonstrate stronger AAs, and the crystals demonstrate weaker AAs compared with that of the corresponding EOs, which is related to the different content of PA in these samples. This study can give some hints for the utilization of such EOs which are abundant in FAs such as PA.

Oestrogen receptor expression in breast cancer (BC) cells is a marker of high cellular differentiation and allows the identification of two BC groups (ER-positive and ER-negative) that, although not completely homogeneous, differ in biological characteristics, clinical behaviour and therapeutic options. The study, based on three publicly available EWAS datasets, focuses on the comparison between these two groups of breast cancer using an epimutation score. The score is calculated not only based on the presence of the epimutation but also on the deviation amplitude of the methylation outlier value. For each dataset, we performed a functional analysis based first on the functional gene region of each annotated gene (we aggregated the data per gene region TSS1500, TSS200, first-exon, body-gene identified by the information from the Illumina Data Sheet) and then we performed a pathway enrichment analysis through the REACTOME database based on the genes with the highest epimutation score. Thus, we blended our results and found common pathways for all three data sets. We found that a higher and significant epimutation score due to hypermethylation in ER-positive BC is present in the promoter region of the genes belonging to the SUMOylation pathway, the NOTCH pathway, the IFN-$\gamma$ signalling pathway and the deubiquitination protease pathway; while a higher and significant level of epimutation due to hypomethylation in ER-positive BC is present in the promoter region of the genes belonging to the ESR-mediated pathway. The presence of this state of promoter hypomethylation in the ESR-mediated signalling genes is consistent and coherent with an active signalling pathway mediated by oestrogen function in the group of ER-positive BC. SUMOylation and NOTCH pathways are associated with BC pathogenesis and have been found to play distinct roles in the two BC subgroups. We speculated that the altered methylation profile may play a role in regulating signalling pathways with specific functions in the two subgroups of ER-BC.

The circuitry of the summarized "floating" differential stages (FDS) based on complementary field-effect transistors with a control p-n junction (CJFET), intended for use in low-noise analog microcircuits, for example, operational amplifiers. The results of modeling the flow characteristics of one of the CJFET FDSs in the LTSpice XVII environment at low temperatures (down to -197 ⁰С) and exposure to a neutron flux in the range of 1e13 ÷ 1e15 n / cm² are presented.

The article presents the author's results of studying hidden rules of structural organizations of long DNA sequences in eukaryotic and prokaryotic genomes. The results concern some rules of percentages (or probabilities) of n-plets in genomes. To reveal such rules, the author considers genomic DNA nucleotide sequences as multilayers sequences of n-plets and studies the percentage contents of n-plets in different layers. Unexpected rules of invariance of total sums of percentages in certain tetra-groupings of n-plets in different layers of genomic DNA sequences are revealed. These discovered rules are candidates for the role of universal genomic rules. A tensor family of matrix representations of interrelated DNA-alphabets of 4 nucleotides, 16 doublets, 64 triplets, and 256 tetraplets is used in the study. This matrix approach allows revealing algebraic properties of the mentioned genetic rules of probabilities, which are useful for developing algebraic and quantum biology. Some analogies of the discovered genetic phenomena with phenomena of Gestalt psychology are noted and discussed. The author connects the received results about the genomic percentages rules with a supposition of P. Jordan, who is one of the creators of quantum mechanics and quantum biology, that life's missing laws are the rules of chance and probability of the quantum world. Additional attention is paid to the algebraic features of the system of structured DNA alphabets and their relationship with the methods of algebraic holography, known in the technique of processing discrete signals. The concept of algebraic-holographic genetics is being developed for the understanding of inherited holographic properties of organisms.

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K⁺ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K⁺ ions are at least 10,000 times more permeant than Na⁺ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na⁺ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

We introduce a new class of Vertex Operator Algebras Y+ and their duals, which generalize the standard W-algebras WN of type sl(N). These algebras can be defined in terms of junctions of boundary conditions and interfaces in the GL-twisted N = 4 Super Yang Mills gauge theory. The aim of these technical calculations is to find the relation of these ortho-symplectic Y-algebras to truncations of even W\infinity.

We prove general stability theorems for $n$-dimensional quartic-cubic-quadratic-additive type functional equations of the form \begin{eqnarray*} \sum_{i=1}^\ell c_i f \big( a_{i1}x_1 + a_{i2}x_2 + \cdots + a_{in}x_n \big) = 0 \end{eqnarray*} by applying the direct method. These stability theorems can save us much trouble of proving the stability of relevant solutions repeatedly appearing in the stability problems for various functional equations.

Arylamine N-acetyltransferases (NATs) are cytosolic enzymes, highly polymorphic, present in both eukaryotes and prokaryotes. These enzymes play an important role in the detoxification and activation of xenobiotics as well as in the synthesis of endogenous compounds. Specific NATs have been pointed out in the literature as possible therapeutic targets. In particular, the human NAT1, for the treatment of certain cancers, and the NAT from M. tuberculosis (TBNAT), for the treatment of tuberculosis. This paper describes an in silico approach to prospect and select potentially inhibitors of NAT1 and TBNAT from the Traditional Chinese Medicine (TCM) using free available tools. A library with ligands from TCM was previously screened in order to select only compounds with optimal pharmacological properties. The affinity of the selected ligands with respect to NAT enzymes was then evaluated by virtual screening (VS). Subsequently, the complexes with the best ligands were submitted to molecular dynamics (MD) simulations aiming to obtain better quality information on affinity and selectivity. The results for one specific ligand, ZINC14690579, indicated its potential for affinity and selectivity. ZINC14690579 structure may represent the discovery of a new scaffold for future development of NAT inhibitors.

As matrix representations of magic labelings of related hypergraphs, magic squares and their various variants have been applied to many domains. Among various subclasses, trimagic squares have been investigated for over a hundred years. The existence problem for trimagic squares with singly even orders and orders 16n has been solved completely. However, very little is known for the existence of trimagic squares with other even orders except for the only three examples and three families. We construct normal trimagic squares by using product constructions, row-square magic rectangles, and trimagic pairs of orthogonal diagonal Latin squares. We give a new product construction: For positive integers p, q, and r having the same parity other than 1, 2, 3, 6, if normal p × q and r × q row-square magic rectangles exist, then a normal trimagic square with order pqr exists. As its application, we construct normal trimagic squares of orders 8q^3 and 8pqr for all odd integers q not less than 7 and p,r ∈ {7, 11, 13, 17, 19, 23, 29, 31, 37}. Our construction can easily be extended to construct multimagic squares.

Systematic results of lattice dynamical calculation are reported for the novel (SiC)m/(GeC)n superlattices (SLs) by exploiting a modified-linear chain model (M-LCM) and a realistic rigid-ion- model (RIM). By employing the bond polarizability method in the framework of M-LCM, we have simulated Raman intensities for the graded (SiC)10-D/(Si0.5Ge0.5C)D/(GeC)10-D/(Si0.5Ge0.5C)D SLs by carefully integrating interfacial layer thickness D (≡ 0, 1, 2, 3 monolayers (MLs)). The variation of D has initiated considerable up (down) shifts of GeC-, (SiC)-like Raman peaks in the middle of the optical phonon frequency region. With D = 3 MLs, the maximum energy shift (by ~ 47 cm-1) of SiC-like modes has caused substantial changes in the Raman intensity profiles linked to the localization of atomic displacements at the interfacial transition regions. This effect can be considered as a vital tool for authenticating the interfacial structures in technologically important SLs. By using a RIM, we have reported SL phonon dispersions along the growth [001] as well as in the plane [100], [110] perpendicular to the growth. Our simulations of phonons in the acoustic mode region have not only confirmed the formation of minigaps at the zone center and zone edges but also provided evidence of anti-crossing and phonon confinement. Besides examining angular dependence of zone-center optical modes, we have also discussed phonon folding, confinement and anisotropic behavior in (SiC)m/(GeC)n SLs.

Plant N concentration (PNC) has been commonly used to guide farmers in assessing maize (Zea mays L.) N status and making in-season N fertilization decisions. However, PNC varies based on the development stage and therefore a relationship between biomass and N concentration is needed (i.e., critical N dilution curves; CNDC) to better understand when plants are N deficient. A few CNDC have been developed and used for plant N status diagnoses, but have not been tested in the US Midwest. The objective of this study was to evaluate under highly diverse soil and weather conditions in the US Midwest the performance of CNDCs developed in France and China for assessing maize N status. Maize N rate response trials were conducted across eight US Midwest states over three years. This analysis utilized plant and soil measurements at V9 and VT development stages and final grain yield. Results showed that the French CNDC (y=34.0x-0.37, where y is critical PNC, x is aboveground biomass) was better with a 91% N status classification accuracy compared to only 62% with the Chinese CNDC (y=36.5x-0.48). The N nutrition index (NNI), which is the quotient of the measured PNC and the calculated critical N concentration (Nc), based on the French CNDC was significantly related to soil nitrate-N content (R2=0.38-0.56). Relative grain yield on average reached a plateau at NNI values of 1.36 at V9 and 1.21 at VT, but for individual sites ranged from 0.80 to 1.41 at V9 and from 0.62 to 1.75 at VT. The NNI threshold values or ranges optimal for crop biomass production may not be optimal for grain yield production. It is concluded that the CNDC developed in France is suitable as a general diagnostic tool for assessing maize N status in US Midwest. However, the threshold values of NNI for diagnosing maize N status and guiding N applications vary significantly across the region, making it challenging for guiding specific on-farm N management. More studies are needed to determine how to effectively use CNDC to make in-season N recommendations in the US Midwest.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

Home-field advantage (HFA) encompasses all the processes leading to faster litter decomposition in the 'home' environment as compared to that of ‘away’ environments. To determine the occurrence of HFA in a forest and adjacent clear-cut, we set up a reciprocal litter decomposition experiment within the forest and clear-cut for two soil types (Cambisols and Gleysols) in temperate Germany. The forest was dominated by Norway spruce (Picea abies), whereas forest regeneration of European Beech (Fagus sylvatica) after clearcutting was encouraged. Our observation that Norway spruce decomposed faster than European beech in 70-yr-old spruce forest, was therefore most likely related to specialized litter-microbial interaction under existing spruce, and leading to a HFA. The ‘spruce’ microbial biome and soil conditions of original forest were then rapidly changed even after a short-term regeneration following clearcutting, resulting in faster beech decomposition also masking any HFA for spruce, particularly in moisture- and nutrient-deficient Cambisols. Divergence between forest and clear-cut in the Cambisol of their litter δ15N values beyond 9 months, implied litter N decomposition was only initially independent of soil and residual C status. We conclude that clearcutting modifies HFA and helps promote the establishment or regeneration of European beech in this and similar forest mountain upland areas.

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). This suggests that dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

We employ hierarchy of models (HoM) with 2, 3 and 4 parameters to reanalyze the nucleation kinetics in the electrodeposition as quantified by n(t) - “the number of nuclei vs. time” data obtained at different overvoltages from precise experiments on electrodeposition of Hg on two different types of Pt-cathodes by Ivan V. Markov and Evgenia Stoycheva [1]. The obtained two scales, nmax and , are used to rescale the original data mapping it on a master curve in coordinates . Our main result is obtained by studying further the dependence of these two scales on the overvoltage (analogue of supersaturation). Surprisingly, for one of the two cathode types - the “hemispherical single-crystal electrode” (as defined by the authors), there is discontinuity in the “ vs. overvoltage” dependence – an almost horizontal jump from 85 to 86 mV accompanied by a change in the slope of the dependence - it is ~ -1 and ~ -0.5 after. For the other cathode - “plane structureless platinum electrode”,  decreases smoothly. Combined, these two behaviors point at the so called “cusp catastrophe”. We compare our findings with published results on protein nucleation.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.

Organic light-emitting diodes (OLEDs) are energy-efficient; however, the coordinating ligand can affect their stability. Sky-blue phosphorescent Pt(II) complexes with a C^N chelate, fluorinated-dbi (dbi = [1-(2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenyl-1H-imidazole]), and acetylactonate (acac)(1)/picolinate (pic)(2) ancillary ligands were synthesized. The molecular structures were characterized using various spectroscopic methods. The Pt(II) coordination sphere in 2 exhibited a distorted square-planar geometry, with several intra- and inter-molecular interactions involving Cπ⋯H/Cπ⋯Cπ stacking. Complex 1 emitted bright sky-blue light (λmax = 485 nm) with a moderate photoluminescent quantum efficiency of 0.37 and short decay time (6.1 µs) compared to those of 2. Time-dependent density functional theory calculations suggested that the electronic transition of 1 arose from ligand(C^N)-centered π–π* transitions combined with metal-to-ligand charge transfer transitions (MLCT), whereas that of 2 arose from MLCT and ligand(C^N)-to-ligand(pic) charge transfer (LLCT), with minimal contribution from the C^N chelate to the lowest unoccupied molecular orbital. Multi-layered phosphorescent OLEDs using 1 as a dopant and a mixed host, 3,3-di(9H-carbazol-9-yl)-1,1-biphenyl:3-di(9H-carbazol-9-yl)-1,1-biphenyl (mCBP)/9-(3’-carbazol-9-yl-5-cyano-biphenyl-3-yl)-9H-carbazole-3-carbonitrile (CNmCBPCN) were successfully fabricated. At a 10% doping of 1, a current efficiency of 13.6 cd A−1 and external quantum efficiency of 8.4 % at 100 cd m−2 were achieved. These results show that the ancillary ligand in phosphorescent Pt(II) complexes must be considered.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

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.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

In addition to nucleic acids, various viral proteins are involved in the assembly of virion. If it is possible to create a biologically active agent that leads to the degradation of one of the key proteins for virus assembly and/or destroys the viral factory, then this agent will effectively cope with virus replication. One of these key proteins for the SARS-CoV-2 virus is the nucleocapsid protein (N-protein). As such a bioactive agent, we offer a modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic to the N-protein, contains an amino acid sequence for the attraction of the Keap1 E3 ubiquitin ligase. This should lead to the subsequent degradation of the N-protein. We have shown that functional properties of modules within the MNT permit its internalization into target cells, endosome escape into the cytosol, and binding to the N-protein. Using flow cytometry and Western blot, it was demonstrated that significant degradation of N-protein is observed when A549 and A431 cells transformed with N-protein are incubated with the developed MNTs. The proposed MNTs open up a new approach for the treatment of viral diseases.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine learning-based computational methods such as eSkip-Finder have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce computational burden and improve prediction performance by using feature selection within machine learning algorithms and ensemble learning techniques. We evaluated our approach using a dataset of experimentally validated exon skipping events, dividing it into training and testing sets. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a powerful tool for examining the function of genes and exons in basic research, as well as gene therapy. Computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping using machine learning. However, these methods can be computationally demanding and the prediction accuracy of the tool is not yet optimal. In this study, we propose an approach to reduce computational burden and improve prediction performance by utilizing feature selection within machine learning algorithms and employing ensemble learning techniques. The method was evaluated using a dataset of genes with experimentally validated exon skipping events. The dataset was divided into training and testing sets to assess the accuracy of the algorithm. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. These findings suggest that this approach has the potential to enhance the efficiency and accuracy of predicting ASO efficacy via exon skipping, facilitating the development of novel therapeutic strategies.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.