The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

The use of nitrogen (N) fertilizers can have detrimental effects on the environment due to nitrate leaching. This study aims to examine the impact of N fertilizer source and application timing on wheat yield and nitrate leaching in various soil textures. A randomized complete block design (RCBD) was employed to conduct the experiment. The treatments consisted of two N fertilizer sources: ammonium nitrate (AN) and urea (NN), applied at three different times throughout the year, with a control treatment. The three application timings were total application before sowing (T₁), total application in spring (T₂), and half the amount before sowing and the other half in spring (T₃). The experiment was conducted in three different soil textures (sandy loam, silty clay loam, and silty clay), with three replications over three growing seasons: 2018-19 (Y₁), 2019-20 (Y₂), and 2020-21 (Y₃). The results indicated significant effects of different soil textures on grain yield. Specifically, the silty clay loam soil differed significantly from the sandy loam and silty clay soils in terms of grain yield. The interaction effects between the N fertilizer source and application timing were also found to be significant for all soil textures (p<0.01). In sandy loam and silty clay soils, the grain yield increased when using the T₃ application timing compared to the silty clay loam soil. Notably, the silty clay loam soil with the T₂ application timing exhibited the highest grain yield, with a yield of 6863.6 kg ha^-1. Furthermore, the study revealed that N fertilizers and their application timing significantly influenced the protein content in the silty clay and sandy loam soils. The protein percentages were 10.76 and 10.93 for the silty clay and sandy loam soils, respectively, following the T₂ treatment. Additionally, ammonium nitrate (AN) demonstrated a noticeable effect on the percentage of grain protein compared to urea (NN). In conclusion, the application timing of N fertilizers had an impact on grain yield and protein content in different soil textures. Moreover, nitrate concentration increased throughout the experiment, with the highest soil nitrate concentration observed in both fertilizer treatments, particularly in the sandy loam soil.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone (HTL) and N-Hcy-protein (N-Hcy). However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of HTL, N-Hcy, and Hcy on the PHF8/H4K20me1/mTOR/autophagy pathway in human umbilical vein endothelial cells (HUVEC). We found that treatments with HTL, N-Hcy, or Hcy significantly reduced PHF8 protein and mRNA expression, increased H4K20me1, and upregulated mTOR signaling. Autophagy was also impaired (significantly downregulated BECN1, ATG5, ATG7, and LC3 protein and mRNA levels). We also found that these changes were mediated by PHF8-targeting microRNA (miR): miR-22-3p and miR-1229-3p. The effects of HTL, N-Hcy, or Hcy on the miR expression and on the PHF8/H4K20me1/mTOR/autophagy pathway were abrogated by treatments with an inhibitor of miR-22 or miR-1229. Taken together, these findings show that Hcy metabolites can upregulate miR-22-3p and miR-1229-3p expression, which then dysregulate the PHF8/H4K20me1/mTOR/autophagy pathway, important for vascular homeostasis.

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

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.

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.

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.

Let R be a commutative ring and m, n be positive integers. We define a proper submodule N of an R-module M to be (m,n)-closed if for r∈R and b∈M, r^{m}b∈N implies rⁿ∈(N:_{R}M) or b∈N. This class of submodules lies properly between the classes of prime and primary submodules. Many characterizations, properties and supporting examples concerning this class of submodules are provided. The notion of (m,n)-modules is introduced and characterized. Furhermore, the (m,n)-closed avoidance theorem is proved. Finally, the (m,n)-closed submodules in amalgamated modules are studied.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

Let R be a commutative ring with identity and m, n be positive integers. In this paper, we introduce the class of (m,n)-prime ideals which lies properly between the classes of prime and (m,n)-closed ideals. A proper ideal I of R is called (m,n)-prime if for a,b∈R, a^{m}b∈I implies either aⁿ∈I or b∈I. Several characterizations of this new class with many examples are given. Analougus to primary decomposition, we define the (m,n)-decomposition of ideals and show that every ideal in an n-Noetherian ring has an (m,n)-decomposition. Furthermore, the (m,n)-prime avoidance theorem is proved.

Along with the familiar Rossby–Haurwitz waves, two-dimensional flows on the surface of a rotating sphere in the regime of zonostrophic turbulence harbour another class of waves known as zonons. Zonons are wave packets produced by energetic large-scale Rossby–Haurwitz wave modes `enslaving’ other wave modes. They propagate westward with the phase speed of the enslaving modes. Zonons can be visualized as enslaving modes’ `ringing’ in the enslaved ones with the frequencies of the former, the property that renders zonons non-dispersive. Zonons reside in high-shear regions confined between the opposing zonal jets yet they are mainly attached to westward jets and sustained by the ensuing barotropic instability. They exchange energy with the mean flow while preserving their identity in a fully turbulent environment, a feature characteristic of solitary waves. The goal of this study is to deepen our understanding of zonons’ physics using direct numerical simulations, a weakly non-linear theory, and asymptotic analysis, and ascertain that zonons are indeed isomorphic to solitary waves in the Korteweg - de Vries framework. Having this isomorphism established, the analysis is extended to eddies detected in the atmospheres of Jupiter and Saturn based upon the observed mean zonal velocity profiles and earlier findings that circulations on both planets obey the regime of zonostrophic macroturbulence. Not only the analysis confirms that many eddies and eddy trains on both giant planets indeed possess properties of zonons, but the theory also correctly predicts latitudinal bands that confine zonal trajectories of the eddies.

Wobbling motion as an exotic collective mode in nuclei without axial symmetry, was intensively discussed during the last few years. The observation of the newly proposed transverse wobbling, first reported in $^{135}$Pr and soon after in nuclei from other mass regions, was considered as a significant discovery in low-spin nuclear structure. However, both the reported experimental results and the proposed theoretical models were lively questioned in a series of works devoted to the investigation of the low-spin wobbling mode in the same nucleus. The electromagnetic properties of the $\Delta I=1$ transitions connecting the one- to zero-phonon and the two- to one-phonon wobbling bands in $^{135}$Pr were recently remeasured, demonstrating their predominant $M1$ magnetic character which is in contradiction with the wobbling motion interpretation. These new experimental observables being well reproduced by both quasiparticle-plus-triaxial-rotor model and interacting boson-fermion model calculations, are against the previously proposed wobbling characteristics of the low-spin bands in $^{135}$Pr. On the other hand, we obtained conclusive experimental evidence for the theoretically suggested transverse wobbling bands at medium spin in $^{136}$Nd. The comparison of the experimental data with calculations utilizing the triaxial projected shell model and a new developed particle-rotor model with frozen orthogonal geometry of the active nucleons, supports the description in terms of transverse wobbling of medium-spin bands in triaxial even-even nuclei.

Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.

In this work, a novel heterojunction based on ZnSnO3/ZnO nanofibers was prepared using electrospinning method. The crystal, structural and surface compositional properties of sample based on ZnSnO3 and ZnSnO3/ZnO composite nanofibers were investigated by X-ray diffractometer (XRD), Scanning electron microscope (SEM), X-ray photoelectron spectrometer (XPS) and Brunauer-Emmett-Teller (BET). Compared to pure ZnSnO3 nanofibers, the ZnSnO3/ZnO heterostructure nanofibers display high sensitivity and selectivity response with fast response towards ethanol gas at low operational temperature. The sensitivity response of sensor based on ZnSnO3/ZnO composite nanofibers were 19.6 towards 50 ppm ethanol gas at 225°C, which was about 1.5 times superior than that of pure ZnSnO3 nanofibers, which can be owed mainly to the presence of oxygen vacancies and the synergistic effect between ZnSnO3 and ZnO.

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.

Dimethylformamide (DMF), a polar solvent, is commonly used for preparing graphene/epoxy nanocomposites. While commonly previous research has predominantly highlighted the improvement in physio-mechanical properties of these nanocomposites, the effect of DMF on processing and its direct influence on the final characteristics of MXene/epoxy nanocomposites have not been investigated.This unexplored link between DMF dosage, MXene concentrations, and the final composite properties presents an exciting direction for future research. In this study, a fixed dosage of DMF was used with varying MXene concentrations to fabricate the nanocomposites. To assess the reliability of DMF dosage on the characteristics of the fabricated nanocomposites, various evaluation techniques were employed, including dispersion evaluation, mechanical tests, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), electromagnetic interference (EMI) shielding, and surface roughness measurements. The research outcomes revealed that as MXene concentration increased, the characteristics of the MXene/epoxy nanocomposites, improved across the board, indicating their potential for use in energy storage applications.

Herein, two title compounds, N-Benzoyl-N’-4-cyanophenyl thiourea (I) and N-(4-nitrobenzoyl)-N’-4-cyanophenyl thiourea (II) were synthesized in high yield, via aroyl isocyanate and 4-aminobenzonitrile. The structure of the prepared compounds was characterized by elementary analysis and FT-IR, ¹H, ¹³C NMR spectroscopic methods. Cyclic voltammetric (CV) experiments were performed with glassy carbon electrode. The reduction potential values of different functional group such as nitro, cyano in title compounds were investigated using CV curves.

An extensive thermodynamic study of N-methylformamide (CAS RN: 123-39-7) and N,N-dimethylformamide (CAS RN: 68-12-2), is presented in this work. The liquid heat capacities of N-methylformamide were measured by Tian–Calvet calorimetry in the temperature interval (250 – 300) K. The vapor pressures for N-methylformamide and N,N-dimethylformamide were measured using static method in the temperature range 238 K to 308 K. The ideal-gas thermo-dynamic properties were calculated using a combination of the density functional theory (DFT) and statistical thermodynamics. A consistent thermodynamic description was developed using the method of simultaneous correlation, where the experimental and selected titerature data for vapor pressures, vaporization enthalpies, and liquid phase heat capacities and calculated ide-al-gas heat capacities are treated together to ensure overall thermodynamic consistency of the results. Resulting vapor pressure equation is valid from the triple point to the normal boiling point temperature.

This paper presents a theory on graph topological structure and graph coloring, proving that for any N-order graph structure (with a topological structure similar to ), the maximum number of colors required for coloring is less than or equal to . The Four Color Theorem is just one special case of this theory, with the maximum structure size for a four-color graph being a 4-order structure graph, hence requiring only a maximum of 4 colors for coloring.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

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.

Therapeutic protein engineering has revolutionized medicine by enabling the development of highly specific and potent treatments for a wide range of diseases. This review examines recent advances in computational and experimental approaches for engineering improved protein therapeutics. Key areas of focus include antibody engineering, enzyme replacement therapies, and cytokine-based drugs. Computational methods like structure-based design, machine learning integration, and protein language models have dramatically enhanced our ability to predict protein properties and guide engineering efforts. Experimental techniques such as directed evolution and rational design approaches continue to evolve, with high-throughput methods accelerating the discovery process. Applications of these methods have led to breakthroughs in affinity maturation, bispecific antibodies, enzyme stability enhancement, and the development of conditionally active cytokines. Emerging approaches like intracellular protein delivery, stimulus-responsive proteins, and de novo designed therapeutic proteins offer exciting new possibilities. However, challenges remain in predicting in vivo behavior, scalable manufacturing, immunogenicity mitigation, and targeted delivery. Addressing these challenges will require continued integration of computational and experimental methods, as well as a deeper understanding of protein behavior in complex physiological environments. As the field advances, we can anticipate increasingly sophisticated and effective protein therapeutics for treating human diseases.

Oxidation of a mixture of nonlabelled (14N2H4) and 15N labeled (15N2H4) hydrazine in aqueous solutions produces 14N15N molecules, indicating the intermediate existence of N4H6 or N4H4 dimers with subsequent transfers of H atoms and splitting of lateral N-N bonds. To explain the key part of hydrazine oxidation reaction, the structures, thermodynamics, and electron characteristics of N4H4 molecules in aqueous solution are investigated at CCSD/cc-pVTZ level of theory. We have not found any spontaneous splitting of the bond between lateral nitrogen atoms in tetrazenes N4H4 during geometry optimization. The most probable N4H4 oxidation products are H2N-NH2 and N2, which are obtained by splitting the bond between central nitrogen atoms and so only 15N2 and 14N2 molecules are formed. Additionally, the formation of H3N-NH and N2 oxidation products is also preferred to structures without any N-N fissions. The formation of H2N=N and HN=NH reaction products is energetically less advantageous. Cyclo-N4H4 structures are stable, without any N-N fissions, but their very high Gibbs energies indicate their vanishing abundance in aqueous solution, so their involvement in hydrazine oxidation is highly improbable. Hydrazine oxidation to 14N15N molecules cannot be explained by tetrazene N4H4 intermediates.

A mixture of nonlabeled (14N2H4) and 15N labeled hydrazine (15N2H4) in an aqueous solution is oxidized to 15N2, 14N2, and 14N15N molecules, indicating the intermediate existence of the 14NH2-14NH-15NH-15NH2 with subsequent hydrogen transfers and splitting of side N-N bonds. Structures, thermodynamics, and electron characteristics of various N4H6 molecules in aqueous solutions are investigated using theoretical treatment at the CCSD/cc-pVTZ level of theory to explain the crucial part of the hydrazine oxidation reaction. Most N4H6 structures in aqueous solutions are decomposed during geometry optimization. Splitting the bond between central nitrogen atoms is the most frequent, but the breakaway of the side nitrogen is energetically the most preferred. The N-N fissions are enabled by suitable hydrogen rearrangements. Gibbs free energy data indicate the dominant abundance of NH3... N2... NH3 species. The side N atoms have very high negative charges, which should support hydrogen transfers in aqueous solutions. The only stable cyclo-(NH)4…H2 structure has a too high Gibbs energy and breaks the H2 molecule. The remaining initial cyclic structures are split into hydrazine and HN≡NH or H2N≡N species, and their relative abundance in aqueous solutions is vanishing.

Balanced nitrogen (N) and phosphorus (P) rates coupling with rational fertilization methodology could promote crop N accumulation, N use efficiency and yield production, particularly in semi-arid and arid regions. To test these characteristics, a two-year (2018 and 2019) pot experiment was therefore performed by growing summer maize in a rain-proof glass greenhouse, under 9 combined N (112, 150 and 187 kg ha-1, urea) and P (45, 60, 75 kg ha-1, calcium superphosphate) rates and three contrasting fertilizer placements. The fertilizers were placed by broadcast on soil surface (Broadcast), side band on 4 cm strip soil surface within 7 cm from sowing line (Side band) and deep band on 4 cm strip below 7 cm soil depth within 7 cm from sowing line (Deep band). Results from three maize growth stages (eight-leaf, 45 days after sowing, DAS; tasseling, 60 DAS; and harvest, 115 DAS) showed that leaf, stem, root N accumulation and total soil N were significantly increased under Deep band than under both Side band and Broadcast at N150P60, N187P60, N150P75 and N187P75, but not at N112P45, N150P45, N187P45, N112P60 and N112P75. Significantly greater leaf, stem, and root N accumulations were also displayed at N150 and N187 than at N112 for the same P60 or P75 under Deep band at 60 DAS and 115 DAS, while were for leaf and stem N accumulations at P75 and P60 than at P45 for the same N150 under Deep band at 45 DAS, 60 DAS and 115 DAS. Significantly greater agronomy N use efficiency, partial factor productivity and N use efficiency exhibited under Deep band than under Side band and Broadcast at N150P75 and N187P75, but at N150P60 and N187P60 for NUE only. In addition, leaf, stem, seed, root N concentrations positively correlated with their own N accumulations or soil N concentration at tasseling and harvest stages. Our results demonstrate that a synchronized N150P60, N187P60, N150P75 or N187P75 fertilization rate with Deep band placement can improve soil N availability and root N uptake, and hereby greater aboveground N accumulation, N use efficiency and yield production of maize particularly practical for small-holder farmers globally.

Throughout this paper, we will establish a comprehensive theoretical foundation and rigorously develop the methodology to investigate the structure of quotient ring S/P under the influence of symmetric generalized n-derivations, where S represents an arbitrary ring, and P signifies a prime ideal of S satisfying certain algebraic identities acting on prime ideal P without relying on the assumption of primeness or semi-primeness of the ring.

The seasonal and vertical spatial variation characteristics of total N, NH4+—N and NO3-—N in the soil in Picea mongolica forest at different stand ages were studied. The results showed that: (1) NH4+ —N in the soil in Picea mongolica forest was positively correlated with sample date, soil NO3-—N and forest age (P <0.05), and negatively correlated with soil depth (P < 0.01). NO3-—N in the soil in Picea mongolica forest was negatively correlated with sample date and forest age (P < 0.05), and significantly negatively correlated with soil depth (P < 0.01); (2) the content of NH4+—N is greater than that of NO3-—N in each soil layer of Picea mongolica forest at three forest ages. The correlation analysis showed which had an impact on the content of NH4+—N and NO3-—N in the soil in Picea mongolica forest. The content was lower in February and November, and higher in May and August；(3) The contents of total N, NH4+—N and NO3-—N in the soil of Picea mongolica forest in the three forest ages increased with the depth of soil layer (0-50cm), and showed an overall downward trend. The contents of NH4+—N in the soil layer of young forest (0-10cm, 10-20cm and 20-30cm, 30-40cm and 40-50cm) were significantly different (P＜0.05), and the contents of NO3-—N were also significantly different (P＜0.05), while their contents of middle-aged forest and near mature forest increased with the depth of soil layer, There was no significant difference in the content of NH4+—N; (4) The content of NH4+—N in the soil in Picea mongolica forest generally showed the following change trend near mature forest > middle-aged forest > young forest. The change trend of soil NO3-—N content is consistent with that of the content of NH4+—N in the soil in Picea mongolica forest.

This article aims to present the outcomes of a study focused on collaboratively developing an Innovation Management Model (IMG) tailored for Colombia's leather agro-industrial chain. The study integrates stakeholder participation, prioritization of variables, literature review, and model validation, emphasizing sustainability considerations throughout the process. Methodologically, it involved a literature review using Scopus, focusing on innovation management models, open innovation, and sustainability, particularly within the leather sector. The search identified 43 documents in Scopus, of which 15 were directly relevant; this analysis was complemented by 18 articles from Google Scholar. Three surveys were conducted to prioritize variables, utilizing Lik-ert-scale questions to assess relevance and congruence. Conceptual innovation models were validated graphically. Initial variables were identified, with 53 selected for the entry stage, 36 for the transformation stage, and 31 for the exit stage. These variables were classified for each stage, resulting in three innovation management models for validation. Key findings included 26 critical variables covering aspects such as agricultural and technological innovation in platforms and projects, capacity development, R&D activities, supply chain dynamics, innovation management processes, knowledge and technology integration, business model adaptation for sustainable development, and environmental impact assessment. The prioritized innovation model is in-tended to assist stakeholders in the leather sector's innovation system by promoting open inno-vation strategies, sustainable and regenerative innovation generation, and enhancing strategic and technological capacities. The prioritized innovation model aims to assist stakeholders in the leather sector's innovation system by promoting open innovation strategies, sustainable and re-generative innovation generation, and enhancing strategic and technological capacities.

Reducing fertilizer-N rate, applying nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. However, how these practices affect crop N uptake by regulating the fertilizer-N fate during the growing season is not well understood. We conducted a field 15N tracer study to explore the effectiveness of reduced N application, NI, and straw incorporation on fertilizer-N fates for maize cultivation in Northeast China. The following six treatments were used: 1) no N fertilization (control); 2) 200 kg urea-N ha−1 (100%N); 3) 200 kg urea-N ha−1 and 2400 kg dry-straw ha−1 (100%N+S); 4) 160 kg urea-N ha−1 (80%N, i.e., 20% reduction of N fertilization); 5) 160 kg urea-N ha−1 and nitrification inhibitor (Nitrapyrin) (80%N+NI); 6) 160 kg urea-N ha−1, nitrification inhibitor and 2400 kg dry-straw ha−1 (80%N+NI+S). Our results showed that the five N fertilization treatments yielded 16%–25% more grain and 39%–60% more crop N uptake than the control receiving no N fertilizer, but the differences among the five treatments were not statistically significant. In contrast to plant growth, changes in fertilizer-N fates in soil and plant pools were more pronounced. Compared with the 100%N treatment, 20% fertilizer-N reduction (80%N) decreased 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (N use efficiency, NUE15N, 60% vs. 50%) (P &lt; 0.05). Nitrapyrin co-application (80%N+NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly (P &lt; 0.05). Straw incorporation (100%N+S) decreased fertilizer-N retention compared with NI co-application because it promoted NUE15N significantly (P &lt; 0.05). The combined application of NI and straw (80%N+NI+S) was more conducive to fertilizer-N retention in soil. Our findings demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Besides, recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines. S100P was shown to be the S100 protein most actively involved in interactions with some of four-helical cytokines. To assess selectivity of S100P protein binding to four-helical cytokines, we have probed interaction of Ca2+-bound recombinant human S100P with a panel of 32 four-helical human cytokines covering all structural families of this fold, using surface plasmon resonance spectroscopy. 22 cytokines from all families of four-helical cytokines are S100P binders with the equilibrium dissociation constants, Kd, ranging from 1 nM to 3 µM (below the Kd value for the S100P complex with the V domain of its conventional receptor, receptor for advanced glycation end products, RAGE). Molecular docking and mutagenesis studies revealed the presence in the S100P molecule of a cytokine-binding site, which overlaps with the RAGE-binding site. Since S100 binding to four-helical cytokines inhibits their signaling in some cases, the revealed ability of S100P protein to interact with ca 71% of the four-helical cytokines indicates that S100P may serve as a poorly selective inhibitor of their action.

Reflection on the training needed by Panamanian teachers has little research tradition, although recently, training programs have been developed for teachers to teach mathematics in accordance with current trends in the teaching of this subject. This article explains one of these postgraduate training programs. Specifically, the guidelines for its design and some results of its second implementation are discussed. Among the most important results for this article we have a) the creation of the platform as well as the set of assignments designed, which have been used for the training of subsequent promotions of teachers; b) It highlights the change in the criteria that guide the teacher's practice at the end of the program, in relation to the criteria used before the training, particularly emphasizing the relevance acquired by the emotional aspects and those related to interaction in this process.

Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts , but their overgrowth can lead to infection in the urogenital tract and at distal sites. Treatment of Ureaplasma spp. infections is difficult. The lack of a cell wall confers resistance to all β-lactam and glycopeptide antibiotics whereas the lack of de novo synthesis of folic acid makes them resistant to sulfonamides and diaminopyrimidines. Thus, there is a need to search for new drugs effective against these bacteria. In the presented studies, the effect of N,N-diethyldithiocarbamate (DDC) at a concentration of 2 µg/ml, 20 µg/ml and 200 µg/ml on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested. Our results indicated that all DDC concentrations used showed both bacteriostatic and bactericidal activity against both tested strains In brief, for the first time we showed the bacteriostatic and bactericidal activity of DDC against Ureplasma urealyticum and Ureaplasma parvum. Based on literature data, we conclude that this DDC activity is related to the inhibition of urease activity, which is an indispensable enzyme for these bacteria. Further research is needed and the results obtained in the present study should be verified in in vivo models of infection.

Substituted bis(iminophosphoranyl)methanes are CH acidic compounds that can form complexes with formally dianionic central carbon centres. The reaction of H₂C(Ph₂P=NDip)₂ (≡ H₂L), Dip = 2,6-diisopropylphenyl, with one equivalent of di-n-butylmagnesium afforded the methanide complex [HLMgnBu] 1. Treatment of complex 1 with phenylsilane in aromatic solvents at elevated temperatures afforded the methanediide complex [(LMg)₂] 2 presumably via the MgH intermediate [(HLMgH)_n] (n = 1 or 2). The reaction of 1 with LiAlH₄ in diethyl ether yielded the AlH complex [HLAlH₂] 3. Alternatively, this complex was also obtained from the reaction of H₂L with AlH₃∙NMe₃. The molecular structures of [HLMgnBu] 1, [(LMg)₂] 2, and [HLAlH₂] 3 are reported. Complex 3 shows no sign of H₂ elimination to a methanediide species at elevated temperatures in contrast to the facile elimination of the putative reaction intermediate [(HLMgH)_n] (n = 1 or 2) to form [(LMg)₂] 2. The chemical properties of complex 2 were investigated and this complex appears to be stable against coordination with strong donor molecules.

Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin – the lipid-rich, periodic structure that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes together via homophilic adhesion, forming a dense, macroscopic ultrastructure known as the intraperiod line. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs the formation of myelin. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when is P0 trafficked and modified to enable myelin compaction, and how disease mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.

Transition between the unfolded and native states of the ordered globular proteins is accompanied by accumulation of several intermediates, such as pre-molten globule, wet molten globule, and dry molten globule. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under the conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth from a particular context. The feature of mathematics from the article title is not quite new. Church's thesis, which is known from the beginning of computability theory, is based on the observation that the currently known computable functions are recursive, where the notion of a computable function is informal. It proves that the predicate of the current mathematical knowledge slightly increases the intuitive mathematics. For a set X⊆N whose infiniteness is false or unproven, we define which elements of X are classified as known. No known set X⊆N satisfies Conditions (1)-(4) and is widely known in number theory or naturally defined, where this term has only informal meaning. (1) A known algorithm with no input returns an integer n satisfying card(X)<ω ⇒ X⊆(-∞,n]. (2) A known algorithm for every k∈N decides whether or not k∈X. (3) No known algorithm with no input returns the logical value of the statement card(X)=ω. (4) There are many elements of X and it is conjectured, though so far unproven, that X is infinite. (5) X is naturally defined. The infiniteness of X is false or unproven. X has the simplest definition among known sets Y⊆N with the same set of known elements. We prove that the set X={n∈N: the interval [-1,n] contains more than 29.5+(11!/(3n+1))∙sin(n) primes of the form k!+1} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. 501893∈X. Condition (1) holds with n=501893. card(X∩[0,501893])=159827. X∩[501894,∞)={n∈N: the interval [-1,n] contains at least 30 primes of the form k!+1}. If we add to X some set W satisfying 14≤card(W)≤23, then the following statements hold: X does not satisfy Condition (1), 159827+14≤card(X), the above lower bound is currently the best known, card(X)<ω ⇒ card(X)≤159827+23, the above upper bound is currently the best known, X satisfies Conditions (2)-(5) except the requirement that X is naturally defined. Analogical statements hold, if we add to X the set ⋃_{x∈N, x divides 99!} {k∈N: k-501894 is the x-th element of P(n^2+1)}, where P(n^2+1) denote the set of primes of the form n^2+1. For a non-negative integer n, let θ(n) denote the largest integer divisor of 10^{10^{10}} smaller than n. Let κ:N→N be defined by setting κ(n) to be the exponent of 2 in the prime factorization of n+1. The set X={n∈N: (θ(n)+κ(n))^2+1 is prime} satisfies Conditions (1)-(5) except the requirement that X is naturally defined. Condition (1) holds with n=0^{10^{10}}. We present a table that shows satisfiable conjunctions of the form #(Condition1)∧ (Condition 2)∧#(Condition 3)∧(Condition 4)∧#(Condition 5), where # denotes the negation ¬ or the absence of any symbol. No set X⊆N will satisfy Conditions (1)-(4) forever, if for every algorithm with no input, at some future day, a computer will be able to execute this algorithm in 1 second or less. The physical limits of computation disprove this assumption.

Deep ultraviolet (DUV) light emitting diode (LED) at emission wavelength of 254 nm is inevitable to replace the conventional toxic mercury UV Lamp as demanded by Minamata Convention of 2020. Both the conventional DUV LEDs (C-LED) and tunnel junction (TJ)-based UVC LEDs are suffering from high operating voltages, low hole injection efficiency and efficiency droops. Therefore, p-AlGaN and n-AlGaN layers-based TJ is one of the most promising parts of optical devices and has been widely utilized as carrier tunneling in DUV LEDs to mitigate both the contact resistance for Ohmic contact and low hole injection efficicny at 254 nm emission. Here an approach is presented to electrically manipulate the quantum tunneling probability by exploiting the transported carriers at the interface of n-AlGaN/p-AlGaN TJ with moderate Si and Mg-doping levels and optimized thickness. As a result, the Augur recomination rate was sucesfully suppressed and quite high radiative recombination rates were achived in the 254nm TJ-based DUV LEDs, which is attributed the improved holes injection toward the MQWs when compared to C-LED. The internal-quantum efficiency (IQE) of approximately ~ 88% in the TJ-based LED with zero efficiency droop is achived, which is 1.3 times greater than the IQE of approximately ~ 66% in the C-LED with efficiency droop of 53%. Based on our known knowledge, this is the highest reported IQE (88%) at emission wavelength of 254 nm in the AlGaN TJ-based LED with efficiency droop of 0%. It was found that the light output powers (LOP) of TJ-LED increases linearly under the varying current density, whereas in the case of C-LED the LOP changes nonlinearly under varying current density. This is attributed to the lower Augure recombination rate in the MQWs of TJ-based DUV LED. The operating voltages were remarkable reduced from 20 V to 5.4 V under 200 mA operation, which is attributed to the thickness and doping optimization in TJ and better selection of realively lower Al-content in the contact-layer. The demonstrated TJ-based DUV LEDs opens the door to epitaxial growth of high-performance UV emitters in MOCVD and MBE for a plethora of biomedical applications.

The results show that seven types of N-nitrosamines: N-nitrosodiethylamine (NDEA), N-Nitrosopiperidine (NPIP), N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDphA) were reduced after heat treatment of pork steaks marinated with L. plantarum MI-LP1, S. carnosus LM-SC1, S. vitulinus LM-SV1. Selected LAB suppressed the formation of putrescine and spermine, lowered acid and peroxide values, which were significantly lower than in the control samples, then P≤0.05 in all cases. The nitrites and nitrates amounts were significantly decreased in pork steaks samples marinated with L. plantarum MI-LP1 and S. carnosus MI-SV1 strains. These results presented that selected lactic acid bacteria could be used for marinating pork steaks to improve quality characteristics and reduce N-nitrosamine formation during grilling.

A highly-integrated experimental system for plasma decomposition of fuels was built. Experiments were conducted and confirmed that macromolecular chain hydrocarbons were cracked by large-gap dielectric barrier discharge under the excitation of a microsecond-pulse power supply. Alkanes and olefins with a C atom number smaller than 10 as well as hydrogen were found in the cracked products of n-decane (n-C10H22). The combination of preheating and plasma decomposition had strong selectivity for olefins. Under strong discharge conditions, micromolecular olefins were found in the products. Moreover, there was a general tendency that micromolecular olefins gradually accounted for higher percentage of products at higher temperature and discharge frequency.

The present paper contains data on the density (ρ), sound velocity (u), specific heat capacity (c_p ) of the mixture of N,N-dimethylformamide + 1-butanol (DMF + BuOH) determined in the entire concentration range of solution and in the temperature range: (293.15–318.15) K. The analysis of thermodynamic functions such as isobaric molar expansion, isentropic and isothermal molar compression, isobaric and isochoric molar heat capacity, as well as their excess functions (〖 E〗_(p,m)^E,〖 K〗_(S,m)^E,〖 K〗_(T,m)^E,〖 C〗_"p,m" ^E,〖 C〗_"V,m" ^E) and also V_m^E was undertaken. The analysis of changes in the physicochemical quantities was based on consideration of the system in an aspect of intermolecular interactions with resulting changes in the mixture structure. The results available in the literature are confusing during the analysis and became the reason for our decision to thoroughly examine the system. What is more, for a system whose components are widely used, there is no information in the literature regarding the heat capacity of the tested mixture, which was also achieved and presented in this publication. The conclusions drawn from so many data allow us to approximate and understand the changes that occur in the structure of the system due to repeatability and consistency of the obtained results

Optimizing the nitrogen (N) timings and rate can improve nutrient uptake, and nutrient-efficiencies, especially of N in wheat under the changing climate scenario. Climatic stress in the form of high temperature and drought resulted in the decreased crop physiology and, ultimately, grain yield. Taking the example of rainfed wheat, we quantified the impact of N application rates as full and split-dose at three variable sites of rainfed Pothwar, Pakistan by conducting field experiments for two years (2013-14 and 201-15). Treatments include, T1 = Control (No fertilizer applied), full dose of N applied at the time of crop sowing, i.e. T2 = 50 kg N ha^-1, T3 = 100 kg N ha^-1 and T4 = 150 kg N ha^-1 and split application of N at different timings during different stages of the crop called as split application of N, i.e. T5: Application of 50 kg N ha^-1 (15 kg N ha^-1 (Sowing) : 20 kg N ha^-1 (Tillering) :15 kg N ha^-1 (Anthesis), T6: Application of 100 kg N ha^-1 (30 kg N ha^-1 (Sowing): 40 kg N ha^-1 (Tillering) : 30 kg N ha^-1 (Anthesis) and T7: Application of 150 kg N ha^-1(45 kg N ha^-1 (Sowing) : 60 kg N ha^-1 (Tillering) : 45 kg N ha^-1 (Anthesis). Three study sites include viz. Islamabad (High rainfall with optimum temperature), University Research Farm (URF)-Koont (Medium rainfall with moderate temperature), and Talagang (low rainfall with high temperature). Results showed that the highest stomatal conductance (0.80 mole m^-2 sec^-1), net photosynthetic rate (20.07 μmole m^-2s^-1), transpiration rate (9.58 mmole m^-2s^-1), intercellular CO2 concentration (329.25 μmole CO₂ mol^-1 air), SPAD values (58.86 %) and proline contents (35.42 μg g^-1) were obtained for split application of N (T6 = Split N100) compared to control and full dose of N treatments. Among sites, these physiological traits remained highest at Islamabad and lowest at Talagang, while among years, maximum values of the measured parameters were obtained in 2013-14. A similar trend was observed for crop total N, N efficiencies, and agronomic traits of the crop. Our results suggest that optimum N application rate and its suitable timings can help to harvest real benefits of N as in our findings, split dose resulted in the maximum performance of the crop from physiological parameters to the agronomic traits of the rainfed wheat crop.

Optimizing the nitrogen (N) timings and rate can improve nutrient uptake, and nutrient-efficiencies, especially of N in wheat under the changing climate scenario. Climatic stress in the form of high temperature and drought resulted in the decreased crop physiology and, ultimately, grain yield. Taking the example of rainfed wheat, we quantified the impact of N application rates as full and split-dose at three variable sites of rainfed Pothwar, Pakistan by conducting field experiments for two years (2013-14 and 201-15). Treatments include, T₁ = Control (No fertilizer applied), full dose of N applied at the time of crop sowing, i.e. T₂ = 50 kg N ha^-1, T₃ = 100 kg N ha^-1 and T₄ = 150 kg N ha^-1 and split application of N at different timings during different stages of the crop called as split application of N, i.e. T₅: Application of 50 kg N ha^-1 (15 kg N ha^-1 (Sowing) : 20 kg N ha^-1 (Tillering) :15 kg N ha^-1 (Anthesis), T₆: Application of 100 kg N ha^-1 (30 kg N ha^-1 (Sowing): 40 kg N ha^-1 (Tillering) : 30 kg N ha^-1 (Anthesis) and T₇: Application of 150 kg N ha^-1(45 kg N ha^-1 (Sowing) : 60 kg N ha^-1 (Tillering) : 45 kg N ha^-1 (Anthesis). Three study sites include viz. Islamabad (High rainfall with optimum temperature), University Research Farm (URF)-Koont (Medium rainfall with moderate temperature), and Talagang (low rainfall with high temperature). Results showed that the highest stomatal conductance (0.80 mole m^-2 sec^-1), net photosynthetic rate (20.07 μmole m^-2s^-1), transpiration rate (9.58 mmole m^-2s^-1), intercellular CO₂ concentration (329.25 μmole CO₂ mol^-1 air), SPAD values (58.86 %) and proline contents (35.42 μg g^-1) were obtained for split application of N (T₆ = Split N₁₀₀) compared to control and full dose of N treatments. Among sites, these physiological traits remained highest at Islamabad and lowest at Talagang, while among years, maximum values of the measured parameters were obtained in 2013-14. A similar trend was observed for crop total N, N efficiencies, and agronomic traits of the crop. Our results suggest that optimum N application rate and its suitable timings can help to harvest real benefits of N as in our findings, split dose resulted in the maximum performance of the crop from physiological parameters to the agronomic traits of the rainfed wheat crop.

Reducing meat consumption is better for the environment. Unfortunately, commercial plant-based meat substitutes are often more expensive than meat and thus have not seen widespread adoption. This paper analyzes commercially-available spirulina, soy, pea, and brown rice protein isolates characteristics to provide data for non-meat protein cost reductions. Thermal and rheological properties, viscosity, density, and particle size distribution are analyzed for further study on alternative protein-based food processing. Differential scanning calorimetry analysis produced dry amorphous-shaped curves and paste curves with a more distinct endothermic peak. Extracted linear temperature ranges for processing in food production for spirulina was 70-90ºC; soy protein was 87-116ºC; pea protein was 67-77ºC; and brown rice protein was 87-97ºC. Viscosity analysis determined each protein material was shear-thinning and that viscosity increased with decreased water concentration, with rice being an exception to the latter trend. The obtained viscosity range for spirulina was 15,100-78,000cP; soy protein was 3,200-80,000cP; pea protein was 1,400-32,700cP; and brown rice protein was 600-3,500cP. The results indicate that extrusion is a viable method for further processing of the protein isolates as this technique has a large temperature operating range and variable screw speed. Data provided here can be used to make single or multi-component protein substitutes.

Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbour pathophysiological roles in myelin disease. Many myelin proteins share common attributes, including small size, high hydrophobicity, multifunctionality, longevity, and intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin and correlate these with their various functions, including susceptibility to post-translational modifications, function in protein-protein and protein-membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.

Rabies is a neurological disease that causes between 40,000 and 70,000 deaths every year. Once a rabies patient has become symptomatic, there is no effective treatment for the illness, and in unvaccinated individuals, the case-fatality rate of rabies is close to 100%. French scientists Louis Pasteur and Émile Roux developed the first vaccine for rabies in 1885. If administered before the virus reaches the brain, the modern rabies vaccine imparts long-lasting immunity to the virus and saves more than 250,000 people every year. However, the rabies virus can suppress the host’s immune response once it has entered the cells of the brain, making death likely. This study aims to make use of disorder-based proteomics and bioinformatics to determine the impact that intrinsically disordered protein regions (IDPRs) in the proteome of the rabies virus have on the infectivity and lethality of the disease. This study uses the proteome of Rabies Lyssavirus (RABV) strain Pasteur Vaccins (PV), one of the best understood strains due to its use in the first rabies vaccine, as a model. The study suggests that the high levels of intrinsic disorder in the phosphoprotein (P-protein) and nucleoprotein (N-protein) allow them to participate in creation of the Negri bodies and help this virus suppress the antiviral immune response in the host cells. Additionally, the study suggests that there is a link between disorder in the matrix (M) protein and the modulation of viral transcription. The disordered regions in the M protein have a possible role in initiating viral budding within the cell. Furthermore, we checked the prevalence of functional disorder in a set of 37 host proteins directly involved in the interaction with the RABV proteins. The hope is that these new insights will aid in the development of treatments for rabies that are effective after infection.

Commercial protein supplements are the main sources for the sports nutrition. Nowadays, those protein supplements mainly differ in the ingredients and formulations, possibly affecting the digestion behavior and protein absorption during gastrointestinal digestion. Herein, this work aimed to investigate the gastric digestion behavior and protein hydrolysis of commercial protein supplements by using an in vitro dynamic digestion model. Five commercial protein supplements were selected, including three protein powders and two liquid protein beverages. The results indicated that liquid protein beverages had smaller particle size than protein powder dispersions, and one of the protein powders existed as the microcapsules. During gastric digestion, all samples tended to form aggregates as the pH decreased, and the degree of aggregation was more pronounced in liquid protein beverages than in protein powders, where the intact structure of the microcapsules was gradually disrupted. Protein hydrolysis degree in liquid protein beverages was higher than that in protein powders. One of the liquid products (M20) had the highest protein hydrolysis degree of around 35.74% after 120 min gastric digestion and a half-empty time of 37.82 min. These findings suggest that the formulation and ingredients of commercial protein supplements will affect their digestion behavior, resulting in varying degree of protein hydrolysis. Hence, sports supplements should be carefully designed to provide precise nutrition for the athletes and exercisers.

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies revealed the ability of specific S100 proteins to affect cell signaling via direct interaction with cytokines. Previously, we have revealed binding of ca. 71% of the four-helical cytokines by S100P protein due to the presence in its molecule of a cytokine-binding site, which overlaps with the binding site for S100P receptor. Here we show that another S100 protein, S100A6 (pairwise sequence identity with S100P of 35%), specifically binds numerous four-helical cytokines. We have studied affinity of recombinant forms of 35 human four-helical cytokines covering all structural families of this fold to Ca2+-loaded recombinant human S100A6, using surface plasmon resonance spectroscopy. S100A6 recognizes 26 of the cytokines from all families of this fold with the equilibrium dissociation constants ranging from 0.3 nM to 12 µM. Overall, S100A6 interacts with ca. 73% of the four-helical cytokines studied to date with selectivity equivalent to that for S100P protein, with the differences limited to binding of Interleukin-2 and Oncostatin-M. The molecular docking study evidences presence in S100A6 molecule of a cytokine-binding site, analogous to that found in S100P. The findings argue the presence in some of the promiscuous members of S100 family of a site specific to a wide range of the four-helical cytokines. This unique feature of the S100 proteins potentially allows them to serve as universal inhibitors of signaling of the four-helical cytokines, which could be of value for reduction of severity of the disorders accompanied by excessive release of the cytokines.

The main objective of this study is to compare and investigate the proximate, sensory parameters of the biscuits fortified with (1) whey protein concentrate (WPC), (2) isolated soy protein (ISP) at various proportions as a source of protein enrichment. The fortified biscuits were analysed for sensory and proximate analysis. The study evaluated and compared the effect of fortifying whey protein concentrate and isolated soy protein at various proportions T0 control (0%), T1 (5%), T2 (10%), T3 (15%), T4 (20%). The protein content in both WPC and ISP samples tends to increase, but much higher in WPC formulated biscuits. At 20% WPC the protein content peaked to 29.11%, other nutritional components such as fat, ash, fibre and moisture content of WPC samples increased significantly, whereas no such significant changes were observed and only linear increase of protein content were in ISP fortified samples. The sensory analysis of ISP fortified samples were acceptable up to 10% proportion, exceeding 10% showed unacceptable results, on comparison WPC biscuits were acceptable at all proportions, more desirable at 20% WPC. Conclusively, fortifying biscuits with either WPC or ISP might be a source of protein without any significant effect on the quality of biscuits.

Background: Night-migratory birds sense the Earth´s magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that light-induced formation of a radical-pair in European robin cryptochrome 4a, ErCry4a, is the primary signalling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signalling involving the α-subunit of the cone specific heterotrimeric G protein from European robin. Methods: Protein-protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer. Results: Surface plasmon resonance studies showed direct interaction revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer. Conclusions: Our results suggest that ErCry4a and the G protein also interact in vivo and might constitute the first biochemical signalling step in radical-pair-based magnetoreception.

The quinoline derivative, N-(7-chloro-4-morpholinoquinolin-2-yl)benzamide, was synthesized in a conventional three-step procedure from 4,7-dichloroquinoline using N-oxidation reaction/C2-amidation reaction/C4 SNAr reaction sequence. The structure of the compound was fully characterized by FT-IR, 1H‐, 13C-NMR, DEPT-135°, and ESI-MS techniques. Its physicochemical parameters (Lipinski’s descriptors) were also calculated using the online SwissADME database. Such derivatives are relevant therapeutic agents exhibiting potent anticancer, antibacterial, antifungal, and antiparasitic properties.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P&lt;0.05), left hippocampus volume (LHV, β: -0.02435, P&lt;0.01) and right hippocampus volume (RHV, β: -0.02544, P&lt;0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P&lt;0.05) and LHV (β: -0.01173, P&lt;0.05) and RHV (β: -0.01193, P&lt;0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P&lt;0.05; RHV, β: -0.005527, P&lt;0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

The non-structural protein (NS) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NS and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at NSs1-32, NSs56-82, and NSs207-237. Rationally, three mutant NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NS. Over-expression of wild-type NS in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NS-NP interaction and viral replication. Thus, the present study identified a critical NS site, which could be targeted for development of therapeutic regimens against SFTSV.

This paper focuses on examining a new type of $n$-additive maps called the symmetric reverse $n$-derivations. As implied by its name, it combines the ideas of $n$-additive maps and reverse derivations, with a $1$-reverse derivation being the ordinary reverse derivation. We explore several findings that expand our knowledge of these maps, particularly their presence in semiprime rings and the way rings respond to specific functional identities involving elements of ideals. Also, we provide examples to help clarify the concept of symmetric reverse $n$-derivations. This study aims to deepen the understanding of these symmetric maps and their properties within mathematical structures.

In the framework of fully vertical GaN-on-Silicon device technology development, we report on the optimization of non-alloyed ohmic contacts on the N-polar n+ doped GaN face backside layer. This evaluation is made possible by using patterned TLMs (Transmission Line Model) through direct laser writing lithography after locally removing the substrate and buffer layers in order to access the n+ doped backside layer. As deposited non-alloyed metal stack on top of N-polar orientation GaN layer after buffer layers removal results in poor ohmic contact quality. To significantly reduce the related contact resistances, an HCl treatment is applied prior to metallization under various time and temperature conditions. A 3-minutes HCl treatment at 70°C is found to be the optimum condition to achieve thermally stable high ohmic contact quality. To further understand the impact of the wet treatment, SEM (Scanning Electron Microscopy) and XPS (X-ray Photoelectron Spectroscopy) analysis were performed. XPS revealed a decrease in Ga-O concentration after applying the treatment, reflecting the higher oxidation susceptibility of the N-polar face compared to the Ga-polar face, which was used as a reference. SEM images of the treated samples show the formation of pyramids on the N-face after HCl treatment, suggesting specific wet etching planes of the GaN crystal from the N-face. The size of the pyramids is time-dependent; thus, increasing the treatment duration results in larger pyramids, explaining the degradation of ohmic contact quality after prolonged high temperature HCl treatment.

Let $n \geq 2$ be a fixed integer and $\mathcal{A}$ be a $C^*$-algebra. A permuting $ n $-linear map $ \mathcal{G} : \mathcal{A} ^{n} \rightarrow \mathcal{A} $ is known to be symmetric generalized $n$-derivation if there exists a symmetric $n$-derivation $ \mathfrak{D} : \mathcal{A} ^{n} \rightarrow \mathcal{A} $ such that $ \mathcal{G} \left(x_{1}, x_{2}, \ldots, x_{i} x_{i}^{\prime}, \ldots, x_{n}\right)= \mathcal{G} \left(x_{1}, x_{2}, \ldots, x_{i}, \ldots, x_{n}\right) x_{i}^{\prime}+x_{i} \mathfrak{D} (x_{1}, x_{2},\ldots, x_{i}^{\prime}, \ldots, x_{n})$ holds for all $x_{i}, x_{i}^{\prime} \in \mathcal{A} $. In this paper, we investigate the structure of $C^*$-algebras involving generalized linear $n$-derivations. Moreover, we describe the forms of traces of linear $n$-derivations satisfying certain functional identity.

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

Biochar application to the soil can improve soil quality and nutrient leaching loss. Recent studies have reported that surficial application of biochar to stored swine manure can reduce emissions of odorous compounds and reduce the volatilization loss of ammonia. Our working hypothesis was that the biochar-treated manure application to the soil would decrease nutrient leaching from manure and increase plant-available nutrients. The study objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and other major and minor nutrients. Three biochars (i) neutral pH red-oak (RO), (ii) highly alkaline autothermal corn (Zea mays) stover (HAP), and (iii) mild acidic Fe-treated autothermal corn stover (HAPE) were incubated with swine manure for a month. The biochar-manure mixture was applied in triplicate to soil columns with application rate determined by the P₂O₅-P content in manure or manure-biochar mixtures after the incubation. The ammonium (NH₄⁺), nitrate (NO₃^-), and reactive P concentrations in soil column leachates were recorded for eight leaching events. Soil properties and plant-available nutrients were compared between treatments and control manure & soil. Manure-(HAP&HAPE) biochar treatments significantly increased soil organic matter (OM) and increased soil total C, N, and improved soil bulk density. Concentrations of KCl-extractable NH₄⁺ and NO₃^- significantly increased in HAPE column leachates during this 4-week study and in the soil after the experiment. A significant reduction in soil Mehlich3 Cu was also observed for the manure-HAPE mixture compared with the control. Overall, the manure-biochar incubation enabled biochar to sorb nutrients from manure, and the subsequent manure-biochar mixture application to soil improved soil quality and plant nutrient availability in comparison to conventional manure application to soil. This proof-of-the-concept study suggests that biochars could be used to solve both environmental and agronomic challenges and further improve the sustainability of animal and crop production agriculture.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

Protein tyrosine sulfation (PTS), a vital post-translational modification, facilitates protein–protein interactions and regulates many physiological and pathological responses. Monitoring PTS has been difficult owing to the instability of sulfated proteins and the lack of a suitable method for detecting the protein sulfate ester. In this study, we combined an in situ PTS system with an ultra-high-sensitivity polysilicon nanowire field-effect transistor (pSNWFET)-based sensor to directly monitor PTS formation. A peptide containing the tyrosine sulfation site of P-selectin glycoprotein ligand (PSGL)-1 was immobilized onto the surface of the pSNWFET by using 3-aminopropyltriethoxysilane and glutaraldehyde as linker molecules. A coupled enzyme sulfation system consisting of tyrosylprotein sulfotransferase and phenol sulfotransferase was used to catalyze PTS of the immobilized PSGL-1 peptide. Enzyme-catalyzed sulfation of the immobilized peptide was readily observed through the shift of the drain current–gate voltage curves of the pSNWFET before and after PTS. To the best of our knowledge, this is the first study to describe in situ PTS and its direct observation by using semiconductor devices. We expect that this approach can be developed as a next generation biochip for biomedical research and industries.

Proteomics research has become one of the most important topics in the fields of life science and natural science. At present, research on protein–protein interaction networks (PPINs) mainly focuses on detecting protein complexes or function modules. However, existing approaches are either ineffective or incomplete. In this paper, we investigate function module detection mechanisms in PPIN, including open databases, existing detection algorithms and recent solutions. After that, we describe the proposed solution based on simplified swarm optimization (SSO) algorithm and gene ontology knowledge. The proposed solution implements SSO algorithm for clustering proteins with similar function, and imports biological gene ontology knowledge for further identifying function complexes and improving detection accuracy. Furthermore, we use four different categories of species dataset for experiment: Fruitfly, Mouse, Scere, and Human. The testing and analysis result show that the proposed solution is feasible, efficient and could achieve a higher accuracy of prediction than existing approaches.

The PII protein is an evolutionary highly conserved regulatory protein from bacteria to higher plants. In bacteria it modulates the activity of several enzymes, transporters and regulatory factors by interacting with them and thereby regulating important metabolic hubs like carbon/nitrogen homeostasis. More than two decades ago the PII protein was characterized for the first time in plants, but its physiological role is still not sufficiently resolved. To gain more insights into the function of this protein, we investigated the interaction behaviour of AtPII with candidate proteins by BiFC and FRET/FLIM in planta and with GFP/RFP traps in vitro. In the course of these studies we found that AtPII interacts in chloroplasts with itself as well as with known interactors like NAGK in dot-like aggregates, which we named PII foci. In these novel protein aggregates AtPII interacts also with yet unknown partners, which are known to be involved in plastidic protein degradation. Further studies revealed that the C-terminal part of AtPII is crucial for the formation of PII foci. Altogether, the presented results indicate a novel mode of interaction for PII proteins with other proteins in plants, which may be a new starting point for the elucidation of physiological functions of PII proteins in plants.

In this study, Fe, N co-doped biochar (Fe@N co-doped BC) was synthesized by carbonization-pyrolysis method and used as carbocatalysts to activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. In the Fe@N co-doped BC/PMS system, the degradation rate of SMX (10.0 mg⋅L−1) was 90.2% within 40 min under optimal conditions. The radical quenching experiments, and electron spin resonance (ESR) analysis suggested that sulfate radicals (SO4•−), hydroxyl radicals (•OH) and singlet oxygen (1O2) participated in the degradation process. After the reaction, the proportion of pyrrolic N apparently decreased from 57.9% to 27.1%. Pyrrolic N served as active sites to break the inert carbon network structure and promote the generation of reactive oxygen species (ROSs). Besides, pyrrolic N showed stronger interaction with PMS and significantly reduced the activation energy required for the reaction (∆G = 23.54 kcal/mol). The utilization potentiality of Fe@N co-doped BC was systematically evaluated in terms of its reusability, and selectivity to organics. Finally, the intermediates of SMX were also detected.

Pyrazinacenes are linearly fused heteroaromatic rings, with N atoms replacing all apical CH moieties. Component rings may exist in a reduced state having NH groups instead of N, causing cross-conjugation. These compounds have interesting optical and electronic properties, including strong fluorescence in the near infrared region and photocatalytic properties, leading to diverse possible applications in bio-imaging, organic synthesis as well as obvious molecular electronic uses. In this study, we have investigated the behaviour of seven-ring pyrazinacene 2,3,11,12-tetraphenyl-7,16-dihydro-1,4,5,6,7,8,9,12,13,14,15,16,17,18-tetradecaazaheptacene (Ph4H2N14HEPT) with emphasis on protic processes including oxidation, tautomerism, deprotonation and protonation, and the species resulting from those processes. We have used computational methods to optimize the structures of the different species and generate/compare molecular orbital structures. Aromaticity of species generated by the different processes has been assessed using the nucleus independent chemical shifts, and trends in the values have been associated with the different transformations of the pyrazinacene core. The computational data was compared with experimental data obtained from synthetic samples of the molecule tBu8Ph4H2N14HEPT.

In this paper, we concentrate on the study of the properties of residual Tsallis entropy for order statistics. Order statistics have an important role in reliability structural engineering for example for modelling lifetimes of series and parallel systems. The residual Tsallis entropy of ith order statistic from a continuous distribution function and its deviation from the residual Tsallis entropy of ith order statistics from a uniform distribution is investigated. In a mathematical framework, a method to express the residual Tsallis entropy of the ith order statistic from a continuous distribution in terms of the residual Tsallis entropy of the ith order statistic from a uniform distribution is provided. This approach may provide insight into the behavior and properties of the residual Tsallis entropy for order statistics. Further, we study the monotonicity properties of the residual Tsallis entropy of order statistics under dierent conditions. By studying these properties, deeper understanding of the relationship between the position of order statistics and the resulting residual Tsallis entropy is gained.

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

Li⁺-conducting polyethylene oxide-based membranes, incorporating the N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide, are as electrolyte separators for all-solid-state lithium polymer batteries operating at medium-high temperatures. The incorporation of the ionic liquid remarkably improves the thermal, ion-transport and interfacial properties of the polymer electrolyte, which, in combination with the wide electrochemical stability even at medium-high temperatures, allow high current rates without any appreciable lithium anode degradation. Battery tests carried out at 80 °C have shown excellent cycling performance and capacity retention even at high rates, never tackled by ionic liquid-free polymer electrolytes. No dendrite growth onto the lithium metal anode was observed.

Abstract: Background: Hemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX), Hx have important implication in hemolytic disorders and hemorrhagic condition because the release of hemoglobin increase labile heme, which is potentially toxic producing oxidative stress. Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped interaction sequences of Hx with hemin and hemoglobin (2) Methods: Spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin, a library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. In silico approach was performed to analyze amino acid frequency in identified interaction regions, and molecular docking was applied for protein-protein interaction (3) Results: Seven linear peptide sequences in Hx were identified to bind hemin (H1-H7), and five were described for Hb (Hb1-Hb5) interaction, with just two sequences shared between hemin and Hb. Amino acid composition of identified sequences demonstrated that Histidine residues are relevant for heme binding, H105, H293, H373, H400, H429, and H462 was distributed in H1-H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx association with the β-chain of Hb, with several hot spot amino acids that coordinated interaction. (4) Conclusions: This study highlights new insights on Hx-hemin binding motifs and protein-protein interactions with Hb. Binding sequences and identified specific peptides can be used for therapeutic purposes and diagnostics, as hemopexin is under investigation to treat different diseases, and there is an urgent need for diagnostics of labile heme for monitoring hemolysis.

Studies on Protein-Protein interactions (PPI) can be helpful for the annotation of unknown protein function and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years for the characterization of Mycobacterium tuberculosis PPI to further decipher TB pathogenesis. This review aims at compiling the most striking results based on in vivo methods (yeast and bacterial two-hybrid systems, protein complementation assays) for the specific study of PPI in mycobacteria. Moreover, newly developed methods, such as in-cell native mass resonance and proximity-dependent biotinylation identification, will have a deep impact on future mycobacterial research, as they are able to perform dynamic (transient interactions) and integrative (multiprotein complexes) analyses.

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated by bioinformatics tools the protein structure and the possible effects of the known variations reported in public databases. Following a procedure already established, we created a 3D model of the whole protein and modelled the structure of 105 protein variants due to known point mutations. The effects of the amino acid substitution at the level of impact on protein structure, stability, and possibly function, were detected by the bioinformatics procedure and described in detail. A web application was implemented to browse the results of the analysis and visualize the 3D models, with the opportunity of downloading the models and analyze by the own software. Among 105 amino acid substitutions investigated, the study evidenced in 44 cases at least one change in any of the investigated structural parameters. Other 6 variations are also relevant, although a structural effect is not detected by our analysis, because they substituted amino acids highly conserved, which suggests a possible function role. All these variations should be the object of particular attention, as they may induce loss of functionality in the protein.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

Long-term potentiation (LTP) is a molecular basis of memory formation. Here, we demonstrate that LTP critically depends on muscle fructose 1,6-bisphosphatase 2 (Fbp2) – a glyconeogenic enzyme and moonlighting protein protecting mitochondria against stress. We show that LTP induction regulates Fbp2 association with neuronal mitochondria and Camk2, and that the Fbp2-Camk2 interaction correlates with Camk2 autophosphorylation. Silencing of Fbp2 expression or simultaneous inhibition and tetramerization of the enzyme with a synthetic effector mimicking the action of physiological inhibitors (NAD⁺ and AMP) abolishes Camk2 autoactivation and blocks formation of the early phase of LTP and expression of the late phase LTP markers. Astrocyte-derived lactate reduces NAD⁺/NADH ratio in neurons and thus, diminishes the pool of tetrameric and increases the fraction of dimeric Fbp2. We therefore hypothesize that this NAD⁺-level-dependent increase of the Fbp2 dimer/tetramer ratio might be a crucial mechanism in which astrocyte-neuron lactate shuttle stimulates LTP formation.

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is a multi-functional protein whose alteration is associated with cancer, Parkinson´s and Alzheimer´s diseases. NQO1 displays a remarkable functional chemistry, capable of binding different functional ligands that modulate its activity, stability and interaction with proteins and nucleic acids. Our understanding on this functional chemistry is limited by the difficulty of obtaining structural and dynamic information on many of these states. Herein, we have used hydrogen/deuterium exchange monitored by mass-spectrometry (HDXMS) to investigate the structural dynamics of NQO1 in three ligation states: without ligands (NQO1apo), with FAD (NQO1holo) and with FAD and the inhibitor dicoumarol (NQO1dic). We show that NQO1apo has a minimally stable folded core holding the protein dimer and with FAD and dicoumarol ligand binding sites populating binding non-competent conformations. Binding of FAD significantly decreases protein dynamics and stabilizes the FAD and dicoumarol binding sites as well as the monomer:monomer interface. Dicoumarol binding further stabilizes all three functional sites, a result not previously anticipated by available crystallographic models. Our work provides an experimental perspective into the communication of stability effects through the NQO1 dimer, valuable to understand at the molecular level the effects of disease-associated variants, post-translation modifications and ligand binding cooperativity in NQO1.

Streptococcus pneumoniae is an pathogenic and opportunistic Gram-positive bacteria that is the leading cause of community acquired respiratory diseases, varying from mild- to deathly- infections. Appearance of antibiotic resistant isolates has prompted the search for novel targets. One of the most promising approaches is the structure-based knowledge of possible targets in conjunction to rational design and docking of inhibitors of the chosen targets. A useful technique to help solving protein structures is to label them with a heavy atom, like selenium, that facilitates tracing of the some of the amino acid residues. We have chosen two pneumococcal DNA-binding proteins, namely the relaxase domain of MobM protein from plasmid pMV158, and the RelB-RelE antitoxin-toxin protein complex. Through the update of a previous protocol [1] that uses seleno-L-methionine, we could achieve 100% labelling of the proteins. Furthermore, the labelled proteins retained full activity as judged from relaxation of supercoiled plasmid DNA and from gel-retardation assays.

Proteins play a major role in biosensors in which they provide catalytic activity and specificity in molecular recognition. The immobilization process is however far from straightforward as it often affects the protein functionality. An extensive interaction of the protein with the surface or a significant surface crowding can lead to changes in the mobility and conformation of the protein structure. This review will provide an insight of how the analysis of the physico-chemical features of the protein surface features before the immobilization process can help to identify the optimal immobilization approach to preserve the functionality of the protein when on the surface of the biosensor.

This study assessed bio-equivalence of high-quality, plant-based protein blends versus Whey Protein Isolate (WPI) in healthy, resistance-trained men. The primary endpoint was incremental area under the curve (iAUC) of blood essential Amino Acids (eAAs) 4 hours after consumption of each product. Cmax and Tmax of blood leucine were secondary outcomes. Subjects (n=18) consumed three plant-based protein blends and WPI (control). Analysis of Variance model was used to assess for bio-equivalence of total sum of blood eAA concentrations. The total blood eAA iAUC ratios of the three blends were: [90% CI]: #1: 0.66 [0.58-0.76]; #2: 0.71 [0.62-0.82]; #3: 0.60 [0.52-0.69], not completely within the pre-defined equivalence range [0.80-1.25], indicative of 30-40% lower iAUC versus WPI. Leucine Cmax of the three blends was not equivalent to WPI, #1: 0.70 [0.67-0.73]; #2: 0.72 [0.68-0.75]; #3: 0.65 [0.62 – 0.68], indicative of a 28-35% lower response. Leucine Tmax for two blends were similar to WPI (#1: 0.94 [0.73-1.18]; #2: 1.56 [1.28-1.92]; #3: 1.19 [0.95-1.48]). The plant-based protein blends were not bio-equivalent. However, blood leucine kinetic data across the blends approximately doubled from fasting concentrations whereas blood Tmax data across two blends was similar to WPI. This suggests evidence of rapid hyperleucinemia, which correlates with a protein’s anabolic potential.

In these days of information overload and high-throughput analysis, it is easy to lose focus on the study of individual proteins. It is our conjecture that such investigations are still crucially important and offer uniquely penetrative insights. We thus present a discussion of biophysical methods to allow readers to get to know their protein of interest better. Although this perspective is not written with the expert in mind, we hope that for interdisciplinary scientists, or researchers who do not routinely perform biophysical analyses, the content will be helpful and inspiring.

Heat Shock Proteins play a crucial role in maintaining cellular integrity during thermal stress conditions, acting as chaperones and participating in the regulation of cellular responses. The focus was to contribute valuable insights into the potential role of hypericin in modulating these heat shock proteins and its implications for anti-tumoral properties. This study employs computational methods, specifically molecular docking, to investigate the potential biological interactions between the chaperone proteins HSP90 and HSC70 and Hypericin, a natural compound recognized for its anti-tumor properties. Despite the limited existing studies in this domain, this research aims to uncover structural insights into the binding mechanisms between Hypericin and these heat shock proteins. In the docking assessments, hypericin demonstrated notable binding energy results, exhibiting a binding energy of -10.5 kcal/mol with Heat Shock Cognate 71 kDa protein and -11.2 kcal/mol with Heat Shock Protein HSP90-alpha.

The aim of this study was to investigate the biochemical properties and gel-forming capacity of duck myofibrillar proteins under the effects of 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-mediated oxidation. Duck myofibrillar proteins were extracted and treated with different concentrations of AAPH solutions (0, 1, 3, 5, 10 mmol/L) and then analysed for carbonyl content, dynamic rheology, protein profiles and gel-forming properties (colour, water holding capacity, hardness, protein profile, microstructure). The results showed that with increasing AAPH concentration, the carbonyl content of protein showed an increasing trend (p &lt; 0.05); SDS-PAGE pattern results indicated that moderate oxidation (3 mmol/L AAPH) induced myosin aggregation via covalent bonds including disulfide, enhanced protein-protein, and thus improved protein-water interactions and gel strength of DMPs heat-induced gels. However, high oxidation (5 and 10 mmol/L AAPH) led to partial degradation of myosin heavy chain (MHC), as evidenced by lower storage modulus and irregular microstructure, which significantly reduced gelation ability. These results suggest that the internal relationship between alkanoperoxy radical-induced oxidation should be taken into account in the processing of duck meat, as mild protein oxidation is conducive to improving gel quality.

Diarrhoea caused by enterotoxigenic Escherichia coli is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhoea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed eleven single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched Lacto-N-neohexaose (Galbeta4GlcNAcbeta6[Galbeta4GlcNAcbeta3]Galbeta4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity.

Proteins having a variety of functions play many essential roles in maintaining various life activities in organisms. Various methods, by which new protein functions can be artificially produced, have progressed rapidly upon development in recombinant DNA technology and effective screening techniques. However, the obtainable scope of the new functions has been restricted in a narrow range, because only functions of presently existing proteins can be used. On the other hand, it has been considered that it would be impossible to create an entirely new protein, which does not show any meaningful homology with any other amino acid sequences of previously existing proteins. The reason is because one amino acid sequence for a protein cannot be selected out from an extraordinary large amino acid sequence diversity as ~10130. As a matter of course, it is impossible to design an amino acid sequence of a protein in advance and a gene encoding the protein cannot be also formed through random process. Nevertheless, extant organisms have generated a variety of entirely new proteins in some way to make full use of them. This means that extant organisms have equipped a mechanism with which entirely new proteins can be produced under the present core life system composed of protein, tRNA (genetic code) and gene. In this article, first I introduce the mechanism, with which entirely new proteins are created in extant organisms, and further propose a novel strategy for application of the mechanism to protein engineering through creation of entirely new proteins, which could contribute to development of various industries.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p&lt; 0.0001) and NAC+Pb groups (p&lt;0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

The objective of this work was to investigate the effect of different soil tillage practices in sunflower cultivation in a rotation system with intercropping Triticosecale x Pisum sativum. For this purpose a two year experimental field of 5% slope was established in central Greece. There were four treatments with three replications each. The treatments were: (a) no tillage - planting parallel to the contour (NTC-PAC), (b) conventional tillage - planting parallel to the contour (CTC-PAC), (c) no tillage - planting perpendicular to the contour (NTC-PEC), (d) conventional tillage - planting perpendicular to the contour (CTC-PEC). During the experiment plant height, leaf area index, specific leaf area, plants’ total nitrogen and plants’ proteins were measured. According to the results plant height ranged from 64.9 (CTC-PAC) to 85.2 cm (NTC-PEC) the 1st year and between 66.5 – 86.5 cm in CTC-PAC and NTC-PEC treatments in the 2nd year. Furthermore, LAI and SLA, plant’s total nitrogen and protein content and N-uptake were affected positively by the no tillage practice. To conclude, sunflower is a promising crop in a rotation system with intercropping Triticosecale x Pisum sativum, cultivating under rainfed sloping conditions.

Inappropriate use of fertilizers is one of the major production constraints in sesame. Studies to optimize the use of N fertilizer on sesame were conducted at Humera Agricultural Research Center (HuARC) under rain fed and irrigation conditions. Thirteen (13) N doses were evaluated in a Randomized Complete Block Design (RCBD) during 2016, 2017 and 2018. In the rain fed condition; results showed higher number of days to 50% flowering on the higher N application. The 31-121.5 kg N ha-1 have scored higher seed yield, where the lower (18 kg N ha-1) and higher (156 kg N ha-1) N doses scored lower seed yield. In the irrigation condition; higher N application rate prolonged the flowering time to some extent and days to 90% maturity was reduced as N rate increased. Heavier seed weights and maximum seed yield were recorded on 64 and 75 kg N ha-1 and the lower N doses scored low seed yield. Agronomic efficiency of N fertilizer (N-AE) was higher on 64 kg N ha-1 under both growing conditions. The partial budget analysis revealed that 64 kg N ha-1 (rain fed) and 75 kg N ha-1 (irrigation) had the higher net profit, MRR and residual ranking. Therefore, for the greater sesame productivity 64 kg N ha-1 has to be recommended for rain fed and 64 to 75 kg N ha-1 for the irrigated sesame.

In no-tillage systems, there is an accumulation of crop residues (CR) which plays an important role in available of soil-N. A study was set up to provide information regarding the CR N credit, and the influence of N mineral fertilizer. An incubation was run in a loam soil with addition of a similar rate of residue (10 Mg ha-1; sugarcane, soybean, and brachiaria) and N mineral fertilizer (urea; 120 kg N ha-1). After the stabilization of biological activity, soil and remaining residues were collected, and N monitored. Results showed that the N credit was positive with application of soybean, sugarcane, and brachiaria. There was an expressive performance of soybean N credit represented by a positive balance, and a reduction from 2.49 to 0.9 g kg-1 of N in residue, with direct increase of 90% of soil-N. There is no need of N fertilizer to potentialize the soybean N credit, but it is requested to potentialize N credit of brachiaria and sugarcane. The urea demonstrated be a good enhancer of brachiaria N credit, but it was not adequate to sugarcane residues. Based in our result, the accumulation and incorporation of CR can be considered as a N credit with positive contribution in soil-N.

The high interest in N-heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. They displayed an effective activity after only 45 minutes of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

Researches on flexible thermoelectric (TE) materials usually focus on conducting polymers (CPs) and CP-based composites; however, it is a great challenge to obtain high TE properties comparable to inorganic counterparts. Here, we report an n-type Ag₂Se film on flexible nylon membrane with an ultrahigh power factor ~987.4 ± 104.1 μWm⁻¹K⁻² at 300 K and an excellent flexibility (93% of the original electrical conductivity retention after 1000 bending cycles around a 8-mm diameter rod). The flexibility is attributed to a synergetic effect of the nylon membrane and the Ag₂Se film intertwined with numerous high-aspect-ratio Ag₂Se grains. A TE prototype composed of 4-leg of the hybrid film generates a voltage and a maximum power of 19 mV and 460 nW, respectively, at a temperature difference of 30 K. This work opens opportunities of searching for high performance TE film for flexible TE devices.

In this work the influence of the structure forming agent on the composition, morphology and oxygen reduction reaction (ORR) activity of Fe-N-C catalysts was investigated. As structure forming agent (SFA), dicyandiamide (DCDA) (nitrogen source) or oxalic acid (oxygen source) or mixtures thereof were used. For characterization, cyclic voltammetry and rotating disc electrode (RDE) experiments were performed in 0.1 M H2SO4. In addition to this, N2 sorption measurements and Raman spectroscopy were performed for the structural characterization. The role of metal, nitrogen and carbon sources within the synthesis of Fe-N-C catalysts has been pointed out before. Here, we show that the optimum in terms of ORR activity is achieved if both N- and O-containing SFAs are used in almost similar fractions. All catalysts display a redox couple, whereat its position depends on the fractions of SFAs. The SFA has also a strong impact on the morphology: Catalysts that were prepared with a larger fraction of N-containing SFA revealed a higher order in graphitization, indicated by bands in the 2nd order range of the Raman spectra. Nevertheless, the optimum in terms of ORR activity is obtained for the catalyst with highest D/G band ratio. Therefore, the results indicate that the presence of an additional oxygen-containing SFA is beneficial within the preparation.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

To investigate the role of sulfhydryl groups and disulfide bonds in different protein-stabilized emulsions, N-ethylmaleimide (NEM) was used as sulfhydryl-blocking agent to be added in the emulsion. The addition of NEM to block the sulfhydryl groups resulted in a reduction of the content of disulfide bonds formation, which enabled destruction of the internal structure of the protein molecule, and then decreased the restriction of protein membrane on the oil droplets. Furthermore, with NEM content increasing in the emulsion, a reduction of protein emulsifying activity and emulsion stability also occurred. At the same time, the intermolecular interaction of the protein on the oil droplet interface membrane was destroyed, and the emulsion droplet size increased with the NEM content in the emulsion. Although NEM blocking sulfhydryl groups not to form disulfide bonds has similar effects on three types of protein emulsion, the degree of myofibrillar protein (MP), egg-white protein isolate (EPI), and soybean protein isolate (SPI) as emulsifier had a subtle difference.

Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with &lt;100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

Transcription factors (TFs) regulate gene expression by recognizing specific target enhancers in the genome. The DNA-binding and regulatory activity of TFs depend on the presence of additional protein partners, leading to the formation of versatile and dynamic multimeric protein complexes. Visualizing these protein-protein interactions (PPIs) in the nucleus is key for decrypting the molecular cues underlying TF specificity in vivo. Over the last years, Bimolecular Fluorescence Complementation (BiFC) has been developed in several model systems and applied for the analysis of different types of PPIs. In particular, BiFC has been applied for analyzing PPIs with hundreds of TFs in the nucleus of live Drosophila embryos. However, the visualization of PPIs at the level of specific target enhancers or genomic regions of interest awaits the advent of DNA-labelling methods that could be coupled with BiFC. Here, we present a novel experimental strategy that we called BiFOR and that is based on the coupling of BiFC with the bacterial ANCHOR DNA-labelling system. We demonstrate that BiFOR enables to precisely quantify the enrichment of specific dimeric protein complexes on target enhancers in Drosophila salivary gland nuclei. Given its versatility and sensitivity, BiFOR could be applied more largely in other tissues during Drosophila development. Our work set up the experimental basis for these future applications.

The concept of the protein powder dispenser was developed on the basis of the results of analyses, studies and customer requirements. The dispenser was assembled using SolidWorks software, which consists of 63 elements, 14 of which are unique parts that are not available on the market. Each part of the dispenser was carefully designed to be injected into the plastic compound. Polypropylene is the perfect material for this dispenser as it is low density, waterproof, insoluble and extremely resistant to tension and bending. High purity propylene polymer can be processed into a tough, rigid and lightweight plastic with relatively low manufacturing costs, replacing expensive materials. The authors' original contributions are the design and manufacture of a dosing device for protein powder, adjustable in 3 heights to be able to dose in containers of different sizes; the design and integration of a mechanism with a precise dosing system, the components being designed so that the parts in contact with the shaft filled with protein powder form a perfectly closed space; the design and integration of the mechanism for adjusting the height of the dispenser.