Plants can utilize the different forms of nitrogen (N), including inorganic and organic N nutrients, and show the great difference in the utilizing efficiency of N-form among species and genotypes within a species. In our previous study, we found that Tibetan wild barley (XZ16) was better in utilization of organic nitrogen in comparison with cultivated barley (Hua30). In this study, metabolite profiles of the two barley genotypes were comprehensively compared in their response to four N forms, including nitrate (NO3-), ammonium (NH4+), urea and glycine. Macro-and micro-nutrient concentrations in shoots were mostly found higher in nitrate and urea treatments than in ammonium and glycine in both the genotypes. XZ16 had higher concentrations of nutrient ions in glycine treatment, but Hua30 accumulated more nutrients in ammonium treatment. Among the total 163 differentially expressed metabolites, highest up-regulation and highest down-regulation was found in XZ16 in glycine and urea treatments respectively. Some important metabolites such as proline, glutamine, serine, asparagine, L-homoserine, aspartic acid, putrescine, ornithine, 4-aminobutyrate were up-regulated in glycine treatment in both the genotypes with higher fold change in XZ16 than in Hua30. Similarly, fructose-6-PO4, aconitic acid and isocitrate were only up-regulated in XZ16 in glycine treatment. Here, we concluded that the genotype XZ16 exhibited higher response to glycine treatment, while Hua30 showed higher response to NH4+ treatment which is attributed to their better utilization of glycine-N and NH4+-N, respectively. .

The article presents comparative results from 5 categories of animals (4 samples originating from pigs, 2 from cows, 1 from chicken, 1 from ostriches, 1 from horses, samples quantified with A, B, C, D, E, F, G, H, I). These samples were collected from large, medium and small (family) farms. The results were validated by the biogas production generated by the respective samples, using the Automatic Methane Potential Test System (AMPTS II) bio-processor. The largest amounts of biogas (2,464.5 Nml, 2,262.0 Nml) were recorded for the samples from pig farms (Sample B and Sample D), whereas the lowest values were obtained in the case of Sample A (414.1 Nml) and Sample C (558.3 Nml). The heavy metals analyzed in the article are Zn, Cu, Fe, Mn, Ca, K, As. The results corroborate that the C/N ratio can also vary to values lower than 20-30, without affecting the biogas production process, and the heavy metal content must be known especially for the full management of the wastes. All final data presented in the article are based on repeated, triplicate experiments, with less as 2% deviation between data.

Ionic liquid MIE-NH2 displays a new role of development of modification of glycoproteins of lactoferrin through a reductive amination mechanism to synthesize versatile pharmaceuticals. This work introduces a new strategy of modification of Lactoferrin by using methylimidazolium N-ethylamine, this ionic liquid MIE-NH2 linked to N-glycans in Lactoferrin derivatives. Using UPLC/ESI-QTOF and MALDI-TOF mass spectrometry to perform and detect the modifying of ionic liquid-linked glycoproteins. Relevantly, modifying the lactoferrin by MIE-H2 as a small molecule of ion liquid lactoferrin (IL-Lf), which could be a potential antiviral drug and it is achieved by inhibiting various targets. The probability of the lactoferrin modified as a small IL-Lf-molecule to inhibit any of these targets was investigated to find out its potency as a SARS-CoV-2 inhibitor. Molecular docking disclosed the activity of modifying glycoproteins - small IL-Lf-molecules containing amino groups and interaction with targeted Mpro, RdRp, TMPRSS2, and PLpro. Clinically, this study shows the a volubility to provide small IL-Lf-molecules as significantly important drugs that target main protease (Mpro), RNA dependent RNA polymerase (RdRp), transmembrane protease serine 2 (TMPRSS2), and Papain-like protease (PLpro).

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

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

Background The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy's efficacy for esophageal cancer patients. Patients and Methods We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated by chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Result Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021 and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62-1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Conclusion Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future.

A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of N-sulfonyl-1,2,3-trizaoles with β-enaminones. The imidazole ring was formed through 1,1-insertion of N-H bond to α-imino rhodium carbene and subsequential intramolecular 1,4-conjugate addition when α-carbon atom of amino group bearing with methyl, whereas utilizing phenyl substituent constructed pyrrole ring via intramolecular nucleophilic addition. Features such as mild conditions, good functional groups tolerance, gram-scale synthesis, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of N-heterocycles.

Recently, spam emails have become a significant problem with the expanding usage of the Internet. It is to some extend obvious to filter emails. A spam filter is a system that detects undesired and malicious emails and blocks them from getting into the users' inboxes. Spam filters check emails for something "suspicious" in terms of text, email address, header, attachments, and language. However, we have used different features such as word2vec, word n-grams, character n-grams, and a combination of variable length n-grams for comparative analysis in our proposed approach. Different machine learning models such as support vector machine (SVM), decision tree (DT), logistic regression (LR), and multinomial naïve bayes (MNB) are applied to train the extracted features. We use different evaluation metrics such as precision, recall, f1-score, and accuracy to evaluate the experimental results. Among them, SVM provides 97.6 \% of accuracy, 98.8\% of precision, and 94.9\% of f1-score using a combination of n-gram features.

Optimization of post polymerization processing of polyolefin elastomers (POE) is of considerable industrial interest. To this aim, experimental determination and theoretical interpretation of the thermodynamics and mass transport properties of POE-solvent mixtures is relevant. Sorption behaviour of n-hexane vapour in a commercial propylene-ethylene elastomer (V8880 VistamaxxTM from ExxonMobil) is addressed here, determining experimentally the sorption isotherms at temperatures ranging from 115 to 140 °C and pressure values of n-hexane vapour up to 1 atm. Sorption isotherms have been interpreted with the Non-Random-Hydrogen-Bonding Equation of State model retrieving, from data fitting, the value of the binary interaction parameter for the n-hexane/V8880 system. Both the case of temperature-independent and of temperature-dependent binary interaction parameter have been considered. Sorption kinetics was also investigated at different pressures and has been interpreted using a Fick’s model determining values of the mutual diffusivity as a function of temperature and of n-hexane/V8880 mixture composition. From these values, n-hexane intra-diffusion coefficient has been calculated interpreting its dependence on mixture concentration and temperature by a semi-empiric model based on free volume arguments.

Maize (Zea mays L.) is the most widely grown important crop in mid altitude areas of intensive maize-based cropping system of western Ethiopia. Agronomic management is the most important input for getting potential yield and high net returns in hybrid maize production. A field experiment was carried out on farmers’ field to find out the effect of varieties (four maize) and nitrogen fertilizer rate (55, 110 kg N ha-1) with one control on yield components and nitrogen use efficiency of different maize varieties in 2013 and 2014 cropping season. It was laid with randomized complete block design in factorial arrangement with three replications. Mean grain yield, thousand seed weight, dry biomass and harvest index of maize varieties were significantly differed among farms and varieties of maize. Application of nitrogen fertilizer rates was significantly increased mean grain yield maize varieties. Interaction of maize varieties with nitrogen fertilizer rates was significantly affected all yield components of maize varieties. Application half and full recommended nitrogen fertilizer gave mean grain yield advantages of 31 and 41 % over control maize varieties planted without nitrogen application. Maize varieties producing higher mean grain yield was also giving higher mean dry biomass. Mean nitrogen up take was varied from 225 to 357 kg ha-1 among varieties of maize. Higher agronomic efficiency of all maize varieties was obtained from maize planted with application half recommended nitrogen fertilizer compared to full recommend. Agronomic efficiency was ranged from 18 to 33 produced among maize varieties. Significantly higher nitrogen up take efficiency of maize varieties was achieved from maize planted with full recommended nitrogen fertilizer application. Considerably higher nitrogen use efficiency of maize varieties was realized from all maize varieties planted with application half recommended nitrogen fertilizer. Application of half recommended nitrogen fertilizer was gave 32 % fertilizer N use efficiency advantage as compared to full recommended nitrogen fertilizer. Maize varieties BH-661>BH-660> BH-543>BH-540>BH-140 were desirable varieties for further promotion work and use by smallholder farmers in mid altitude area of western Ethiopia.

A field experiment was conducted in Ninghe, Tianjin, China, using 15N isotope method to evaluate the application of organic fertilizer on N distribution patterns of labelled and unlabeled N fertilizer, ammonium sulfate -15N uptake by rice, N use efficiency (NUE), and the fate of (15NH4)2SO4 applied. The experiment included eight treatments: CK-N (control + no-duck), CK-D (control + ducks), CF-N (chemical fertilizer + no-ducks), CF-D (chemical fertilizer + ducks), CM-N (chemical fertilizer + organic fertilizer + no-ducks), CM-D (chemical fertilizer + organic fertilizer + ducks), CD-N (chemical fertilizer 30% off + organic fertilizer + no-ducks), and CD-D (chemical fertilizer 30% off + organic fertilizer + ducks). The results showed that the application of organic fertilizer whether CM or CD significantly increased N and P concentrations over control (CK) and chemical fertilizer (CF). Moreover, no-significant differences were found in 15N fresh grain and husk concentration. Both organs ranged of 14.2-14.4 g kg-1 and 6.2-6.3 g kg-1, respectively. N derived from the fertilizer and soil significantly affected fresh grain compared to fresh husk. However, N uptake and N use efficiency did not show any differences. We concluded that organic fertilizer has a significant influence on rice growth and promote crop productivity.

Euglena gracilis is an alga of great biotechnological interest and extensive metabolic capacity, able to make high levels of bioactive compounds, such as polyunsaturated fatty acids, vitamins and β-glucan. Previous work has shown that Euglena expresses a wide range of carbohydrate-active enzymes, suggesting an unexpectedly high capacity for the synthesis of complex carbohydrates for a single-celled organism. Here, we present an analysis of some of the carbohydrates synthesised by Euglena gracilis. Analysis of the sugar nucleotide pool showed that there are the substrates necessary for synthesis of complex polysaccharides, including the unusual sugar galactofuranose. Lectin- and antibody-based profiling of whole cells and extracted carbohydrates revealed a complex galactan, xylan and aminosugar based surface. Protein N-glycan profiling, however, indicated that just simple high mannose-type glycans are present and that they are partially modified with putative aminoethylphosphonate moieties. Together, these data indicate that Euglena possesses a complex glycan surface, unrelated to plant cell walls, while its protein glycosylation is simple. Taken together, these findings suggest that Euglena gracilis may lend itself to the production of pharmaceutical glycoproteins.

The study aimed to investigate the effects of colonization with two arbuscular mycorrhizal (AM) fungi, Funneliformis mosseae , Diversispora versiformis , alone and in combination on the growth and nutrient acquisition of NaCl-stressed Chrysanthemum morifolium (Hangbaiju) plants in the greenhouse experiment. Mycorrhizal and non-mycorrhizal Hangbaiju plants were grown under different salinity levels imposed by 0, 50 and 200 mM NaCl for five months, following 6 weeks of non-saline pre-treatment. The results showed that root length, shoot and root dry weight, total dry weight, shoot and root N concentration were higher in mycorrhizal than in non-mycorrhizal plants under moderate saline conditions especially with D. versiformis colonization. As salinity increased, the mycorrhizal colonization, the mycorrhizal dependence (MD) decreased. Enhancement of tissue N acquisition is probably the main mechanism underlying salt tolerance in AM plants. It is suggested that the symbiotic associations between D. versiformis fungus and C. morifolium plants may be taken as a biotechnological practice in culture.

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappan with methanol extract. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Their biological activities were profiled by their antiplasmodial activity.

Antecedents. EFs (EFs) are the basis for establishing a goal and working towards that goal by coordinating thoughts and actions. EFs are fundamental to several aspects of daily life, specifically for academic performance. Aim. To analyze and compare the development of EFs in the transition period between the first and second cycles of Early Childhood Education. Methodology. Non-experimental methodology, ex post facto design, descriptive, cross-sectional evolution study. Participants. Preschoolers of different educational levels (first and second cycle of Infant Education). In this study the participants have been evaluated by different informants: 54.42% by parents and 45.58% by teachers. In relation to gender, 52.65% were male and 47.35% were female. In relation to age, 37.54% had a range of 2-3 years and 62.46% had a range of 4-5 years. Measurement. Instrument development of EFs were evaluated using BRIEF-P by key informants. Results. Preschoolers in the first cycle show significantly higher scores than preschoolers in the second cycle in BRIEP-P. Conclusions. The development of EF is key in these first key moments, having a special impact on later development and academic performance. It is necessary to work on EFs from the first cycle of Early Childhood Education, considering the evolutionary development of EFs.

Growth hormone therapy (GHT) can improve growth velocity and final height but can also accelerated the process of bone growth, which is related to structural bone modelling, both in formation and resorption. The study evaluated the capacity of bone turnover markers to predict early growth response to one year GHT in short stature children born as small for gestational age (SGA). 25 prepubertal SGA children were included. We have estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type I), P3NP (N-terminal procollagen type III), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA, IRA and ELISA methods. A statistically significant increase in bone resorption markers (Ctx ) was found both at 6 and 12 months. P1NP bone markers increased at 6 months and after 12 months of therapy. The P3NP marker of collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months and similarly ALP. We have found a significant correlation between height (cm) and Ctx after 6 -12 months as well as P1NP / height (SD) after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We find a strong reaction of bone resorption and bone formation markers during growth hormone therapy that may determine their selection as prediction of GH treatment outcome in SGA children. However, the issue requires further research.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild type (WT) and knock out (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. Tail suspension test (TST) was performed in TRPA1 WT and KO animals. C-FOS immunohistochemistry was carried out on TRPA1 WT animals. DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on Trpa1 KO mice. DMTS administration induced neuronal activation in stress-related brain areas such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy in stress-related disorders.

p-Toluenesulfonic acid is commercially available, non-toxic, cheap organic compound with robust stability. p-Toluenesulfonic acid is solid, non-corrosive and a strong organic acid that can be handled easily. Due to this p-toluenesulfonic acid could be the better replacement of other conventional acids like nitric acid, sulfuric acid, perchloric acid and AlCl3 in organic transformations. Moreover, p-toluenesulfonic acid could be used synergistically with other mode of catalysis like transition metal catalysis and photocatalysis. In recent years, the use of this solid organic acid in organic and polymer synthesis has grown tremendously. In this review, we present an overview of p-toluenesulfonic acid promoted various organic reactions with particular emphasis to the more recently reported methods. In some cases, we also detailed the understanding of the reactions by providing the reaction mechanism. Despite these advances, there are still many opportunities for the development of new reactions using PTSA. Industry and academia have become more conscious to adopt sustainable chemical processes using safer reagents and solvents and the use of PTSA in this context is highly significant. This review will inspire researchers for further reaction development employing p-toluenesulfonic acid.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

In this study, we investigate the existence of positive solutions within a system of Riemann-Liouville fractional differential equations that incorporate the (r1,r2,r3)-Laplacian operator while being subject to three-point boundary conditions. These equations incorporate various fractional derivatives and are influenced by parameters represented as (ψ1,ψ2,ψ3). Our approach involves employing techniques such as cone expansion and compression of the functional type, in conjunction with the Leggett-Williams fixed point theorem, to establish the existence of positive solutions. To emphasize the practical significance of our findings in the realm of fractional differential equations, we provide two illustrative examples.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

The paper considers coherent states for the representation of Weyl commutation relations over a field of $p$-adic numbers. A geometric object, a lattice in vector space over a field of p-adic numbers, corresponds to the family of coherent states. It is proved that the bases of coherent states corresponding to different lattices are mutually unbiased, and the operators defining the quantization of symplectic dynamics are Hadamard operators.

A paradigm shift away from null hypothesis significance testing seems in progress. Based on simulations, we illustrate some of the underlying motivations. First, P-values vary strongly from study to study, hence dichotomous inference using significance thresholds is usually unjustified. Second, statistically significant results have overestimated effect sizes, a bias declining with increasing statistical power. Third, statistically non-significant results have underestimated effect sizes, and this bias gets stronger with higher statistical power. Fourth, the tested statistical hypotheses usually lack biological justification and are often uninformative. Despite these problems, a screen of 48 papers from the 2020 volume of the Journal of Evolutionary Biology exemplifies that significance testing is still used almost universally in evolutionary biology. All screened studies tested default null hypotheses of zero effect with the default significance threshold of p = 0.05, none presented a pre-specified alternative hypothesis, pre-study power calculation, and the probability of ‘false negatives’(beta error). The results sections of the papers presented 49 significance tests on average (median 23, range 0–390). Of 41 studies that contained verbal descriptions of a ‘statistically non-significant’ result, 26 (63%) falsely claimed the absence of an effect. We conclude that studies in ecology and evolutionary biology are mostly exploratory and descriptive. We should thus shift from claiming to ‘test’ specific hypotheses statistically to describing and discussing many hypotheses (possible true effect sizes) that are most compatible with our data, given our statistical model. We already have the means for doing so, because we routinely present compatibility (‘confidence’) intervals covering these hypotheses.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

We utilized laser irradiation as a potential technique in tuning the electrical performance of NiOx/SiO2 thin film transistors (TFTs). By optimizing the laser fluence and the number of laser pulses, the TFT performance is evaluated in terms of mobility, threshold voltage, on/off current ratio and subthreshold swing, all of which were derived from the transfer and output characteristics. The 500 laser pulses irradiated NiOx/SiO2 TFT exhibited an enhanced mobility of 3 cm2/V-s from a value of 1.25 cm2/V-s for as-deposited NiOx/SiO2 TFT. The laser-irradiated NiOx material likely has a significant concentration of defect gap states, which could also be involved in light absorption processes. Second, and more importantly, the excess energy that the photogenerated charge carriers possess (due to the significant difference between the photon energy and the bandgap of NiOx), combined with the very high light intensity, would result in complex thermal and photo thermal changes thus resulting in an enhanced electrical performance of p-type NiOx/SiO2 TFT structure.

Increasing evidence suggests that prenatal exposure to opioids can adversely influence brain development, yet, limited data exists on the effects of opioid-exposure on preschool language development. Our study aimed to characterize the nature and prevalence of language problems in children prenatally exposed to opioids, and the factors that support or hinder language acquisition. A sample of 100 children born to pregnant women in methadone maintenance treatment and 110 randomly identified non-exposed children were studied from birth to age 4.5 years. At 4.5 years, 89 opioid-exposed and 103 non-exposed children completed the preschool version of the Clinical Evaluation of Language Fundamentals (CELF-P) as part of a comprehensive neurodevelopmental assessment. Children prenatally exposed to opioid had poorer receptive and expressive language outcomes at age 4.5 years compared to non-exposed children. After adjustment for child sex, maternal education, other pregnancy substance use, maternal pregnancy nutrition and prenatal depression, opioid exposure remained a significant independent predictor of children’s total CELF-P language score. Examination of a range of potential intervening factors showed that a composite measure of the quality of parenting and home environment at 18 months and early childhood education participation at 4.5 years were important positive mediators.

A renewable cyclic monoterpene obtained from citrus peel, limonene is widely used as a fra-grance, nutraceutical ingredient, antibacterial, biopesticide, and green extraction solvent. Indus-trial demand largely exceeds supply. After reviewing recent advances in the recovery of limonene from citrus peel and residues with a particular attention to benign-by-design extractive processes, we focus on the latest results in its dehydrogenation to p-cymene via heterogeneous catalysis.

Distinguishable annual growth rings produce in Pinus roxburghii are an asset to find out the age of individual tree. This paper aimed to determine the age of P. roxburghii through coring samples and test the relationship with forest production. The biomass estimated, girths measured at two different sections and heights measured which allowed to determine the rate of tapering of the stand. The regression analysis was performed to test the relationship between various variables. The mean age of the P. roxburghii stand was found to be 23.97 (~24 years). The result showed the significant (p<0.05) positive correlation coefficient has been seen between age with girth at breast height, biomass, volume and carbon stock. However, no significant (p>0.05) correlation (r = 0.08) was found between age and height of the stand. In contrast, a correlation between diameter at breast height (DBH) was significant (p<0.05) and positive with volume, biomass, but no significant (p>0.05) correlation (r = 0.14) found between DBH and height of the stand. However, height has a significant (p<0.05) positive correlation with biomass. The mean biomass was 375 kg and mean annual increment (MAI) was 15 kg per tree. Rate of tapering of the studied stand predicted to be 3 cm diameter decreased with trunk height running at 100 cm from base to upward of P. roxburghii stand and vice versa. Result suggests that height-age relation is very weak whereas age, DBH, biomass and carbon has a significant correlation signifies that time-based forests' production and potential production estimation can be obtained in a relatively accurate way by utilizing the age of stand. The time-based forest production analysis is pioneer work in Nepal. The study affirms the tree ring count in P. roxburghii would be a credible and accurate method to determine the age of standing trees.

In this work, magnetic CuFe₂O₄/Ag nanoparticles activated by porous covalent organic frameworks (COF) was fabricated to evaluate the heterogenous reduction of 4-nitrophenol (4-NP). The core-shell CuFe₂O₄/Ag@COF was successfully prepared by polydopamine reduction of silver ions on CuFe₂O₄ nanoparticles, followed by COF layer condensation. With integrating the intrinsic characteristics of the magnetic CuFe₂O₄/Ag core and COF layer, the obtained nanocomposite exhibited features of high specific surface area (464.21 m² g^-1), ordered mesoporous structure, strong environment stability, as well as fast magnetic response. Accordingly, the CuFe₂O₄/Ag@COF catalyst showed good affinity towards 4-NP via π-π stacking interactions and possessed enhanced catalytic activity compared with CuFe₂O₄/Ag and CuFe₂O₄@COF. The pseudo-first-order rate constant of CuFe₂O₄/Ag@COF (0.77 min^-1) is 3 and 5 times higher than CuFe₂O₄/Ag and CuFe₂O₄@COF, respectively. The characteristics of bi-catalytic CuFe₂O₄/Ag and the porous COF shell of CuFe₂O₄/Ag@COF made a contribution to improve the activity of 4-NP reduction. The present work demonstrated a facile strategy to fabricate COF activated nano-catalysts with enhanced performance in the fields of nitrophenolic wastewater treatment.

Incidental P losses from non-point sources may contribute to eutrophication and to decreased soil fertility. These incidents have been related to heavy rainfall on freshly fertilized agricultural soils and little is known about such incidents on more natural soils or in forests. The aim of this work is to determine if incidents of high P leaching also occur in spruce forests, and if such incidents are of significance in P cycling. We found a peak in the mineral soil solution showing that single events of high P leaching occur. The orthophosphate concentration in the Bf-horizon of the 80-year old spruce forest peaked in the autumn of the second year of a continuous monitoring. The concentration increased by more than 85 times compared to the highest concentration obtained earlier during the sampling. The amount leached during this 6 months peak is 10 times higher than the average annual leaching. This P leaching might be due to a combination of high P deposition/through-fall and a high anion exchange with dissolved-organic-carbon and Cl-. We suggest that single events of high sub-surface P leaching may contribute to the overall P leaching, and might increase with the global warming as more DOC is expected to be released to the soil solution.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

The synthesis of enantiomeric forms of D-amino acids can be achieved by a two-step "hydantoinase process" based on the sequential catalysis of substrates by specific enzymes, D-carbamoylase and D-hydantoinase. In addition to our previously studied D-hydantoinase, we describe here the structural features of D-carbamoylase from Pseudomonas, the encoded gene of which was chemically synthesized and cloned into Escherichia coli. A significant fraction of the overexpressed recombinant protein forms insoluble inclusion bodies, which are partially converted to a soluble state upon treatment with N-lauroylsarcosine or upon incubation of the cells at low temperatures. Analysis of the substrate specificity of the purified His-tag protein showed that D-carbamoylase exhibits the highest activity toward N-carbamoyl-D-alanine and N-carbamoyl-D-tryptophan. Molecular docking analysis revealed the location of the substrate binding site in the three-dimensional structure of D-carbamoylase. Molecular dynamics simulations showed that the binding pocket of the enzyme in complex with N-carbamoyl-D-tryptophan is stabilized within 100 ns. The free energy of binding indicated a possible role of residues Arg176 and Asn173 in the formation of hydrogen bonds between the enzyme and N-carbamoyl-D-tryptophan. The properties of the studied D-carbamoylase and D-hydantoinase support further development of a combined biotechnological process for the production of new drugs and peptide hormones.

Let R be a commutative ring with identity and S be a multiplicatively closed subset of R. The purpose of this paper is to introduce the concept of weakly S-primary ideals as a new generalization of weakly primary ideals. An ideal I of R disjoint with S is called a weakly S-primary ideal if there exists s∈S such that whenever 0≠ab∈I for a,b∈R, then sa∈√I or sb∈I. The relationships among S-prime, S-primary, weakly S-primary and S-n-ideals are investigated. For an element r in any general ZPI-ring, the (weakly) S_{r}-primary ideals are charctarized where S={1,r,r²,⋯}. Several properties, characterizations and examples concerning weakly S-primary ideals are presented. The stability of this new concept with respect to various ring-theoretic constructions such as the trivial ring extension and the amalgamation of rings along an ideal are studied. Furthermore, weakly S-decomposable ideals and S-weakly Laskerian rings which are generalizations of S-decomposable ideals and S-Laskerian rings are introduced.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin) it seems rational to consider targeting of Pol I or, more generally, rRNA synthesis for treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered as a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood onset neuronal death as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored.

DNA polymerases replicate cell genomes and/or participate in the maintenance of genome integrity. DNA polymerases sharing high sequence homology with E. coli DNA polymerase I (pol I), have been grouped in Family A. Pol I participates in Okazaki fragment maturation and in bacterial genome repair. Since its discovery in 1956, pol I has been extensively studied, primarily to get deeper insights into the mechanism of DNA replication. As research on DNA polymerases advances, many novel functions of this group of polymerases are uncovered. For example, human DNA polymerase θ (a Family A DNA pol) has been shown to synthesize DNA using RNA as a template, a function typically attributed to retroviral reverse transcriptase. A heightened interest in drug discovery against pol θ has emerged due to its roles in cancer. Likewise, Pol I family enzymes also appear attractive drug-development targets against microbial infections. Development of antimalarial compounds targeting apicoplast apPOL, an ortholog of Pol I, further extends the druggability of this family of enzymes. Here, we summarize reported drug-development efforts against Family A polymerases, and future perspective regarding these enzymes as antibiotic targets. Current techniques such artificial intelligence can be used to facilitate the goal of new drugs.

The field of nephrology has recently directed a considerable amount of attention towards the stimulator of interferon genes (STING) molecule since it appears to be a potent driver of chronic kidney disease (CKD). STING and its activator, the cyclic GMP-AMP synthase (cGAS) are among the most relevant inducers that promote the expression of type I interferons (IFN-Is). These cytokines have been long recognized as part of the mechanism used by the innate immune system to battle viral infections; however, their involvement in sterile inflammation remains unclear. Mounting evidence pointing to the involvement of the IFN-I pathway in sterile kidney inflammation provides potential insights into the complex interplay between the innate immune system and damage to the most sensitive segment of the nephron, the glomerulus. The STING pathway is often cited as the cause of renal disease originating from non-infection related caused by the induction of IFN-I expression. However, other receptors have been implicated in this process, mainly by recognizing host-derived nucleic acids. This review explores the main endogenous inducers of IFN-I in glomerular cells, discusses what exposure to the main autocrine and paracrine cytokines has on these cells, and identifies the pathways that are implicated in the development of glomerular damage.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

Copper(I) sulfide (Cu2S) is a low-cost, earth-abundant, and non-toxic thermoelectric material for applications in the middle-high temperature range (&gt;650 K). Although 3D printing these materials can simplify their manufacturing, elevated temperatures observed during sintering impair their crystal structure and energy conversion efficiency. In this study, we demonstrated a novel post-processing methodology to revert the thermoelectric properties of the 3D printed Cu2-xS materials back to the unimpaired state via sulfur infusion. After printing and sintering, sulfur was infused into the specimens under vacuum to optimize their crystal structure and achieve high thermoelectric efficiency. Chemical analysis and X-ray Diffraction (XRD) tests showed that after the sulfur infusion process, the Cu/S ratio was reverted close to the stoichiometric level. 3D printed Cu2-xS showed p-type thermoelectric behavior with electrical conductivity peaking at 143 S-cm-1 at 750 K and Seebeck coefficient of 175 µV-K-1 at 627 K. Figure of merit (ZT) value of 1.0 at 780 K was achieved which is the highest value ever reported for a 3D printed Cu2-xS thermoelectrics at this temperature. Fabrication of environmentally friendly thermoelectric materials with extended dimensional freedom and conversion efficiency has the potential to impact the thermoelectric industry with new energy conversion applications and lowered manufacturing costs.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on their animal model’s data verified by molecular docking, multitarget interactions in network pharmacology, and dynamic simulation assays. The GC-MS characterized tamarind products were administered to the cholesterol-induced hypertensive Wistar albino rat models. Two-week-intervened animals were dissected to collect serum and organs which were respectively subjected to the analyses of hypertension-linked markers and tissue architectures. Lead biometabolites of tamarinds interacted with eight target receptors in molecular docking and dynamic simulation studies and they were tested for multitarget interactions using network pharmacological analyses. Results showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), Troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour over the sweet tamarind flesh extracts, but seed extracts had a smaller influence. Among the tamarind’s biometabolites, Gamma-sitosterol (ϒ-sitosterol) was found to be the best ligand in managing hypertension via the possible ligand-receptor interactions with the guanylate cyclase which displayed the best drug-likeliness through the highest binding energy -9.3 Kcal. Multitargeted interactions-based degree algorithm and phylogenetic tree of pathways showed 14 targeted genes, of which NR3C1, REN, PPARG, and CYP11B1 hub genes, were consistently modulated by the ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 to 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be supplemented to be a more prospective antihypertensive target or nutraceuticals affirming through advanced preclinical and clinical studies.

Soybean is a highly nutritious legume grown globally as a food and feed crop. An examination of a collection of 10 cultivated and 6 wild Korean soybean varieties showed that there is phenotypic variability notable in different soybeans. Therefore, to develop a list of biomarker candidates useful for growing soybeans of better quality and quantity, the genes of 16 Korean soybean varieties were compared with those of the reference Glycine max var. Williams 82. The comparison was made through gene sequencing to facilitate selection of nsSNPs. The objective of the study was to find out the structural and functional variations caused by nsSNPs and discuss whether the collection of Korean soybean varieties qualifies as biomarkers based on their phenotypic traits. Analysis of the data collected was done using four software: SIFT, Polyphen, PANTHER, and I-mutant 2.0, which are designed to detect the rate of functional and structural variations caused by the nsSNPs in cultivated and wild soybean varieties. Genotypic information obtained in the analysis was used to develop a core collection of biomarkers based on whether nsSNP content was found in more than half of the 16 samples. Therefore, the list of biomarker candidates developed from this study showed that Korean soybean could provide valuable information needed in both future crop genetic research and identification of biomarkers.

Dysregulation of the angiotensin-II Type-I receptor (AT1R) and its pathway was reported to associate with poor-prognosis in several malignancies, including colorectal-cancer (CRC). We have explored the therapeutic-potential of targeting AT1R using valsartan, and its pharmacological-interaction with Fluorouracil (5-FU) in CRC. Anti-proliferative function was evaluated in 2-/3-dimensional cells and in vivo models. Anti-proliferative, anti-migratory, apoptotic function and effect on cell-cycle was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing test, and Fluorescence-activated cell sorting (FACS), respectively, while gene-expression was determined at mRNA/protein levels. By histogical analysis and measuring of oxidative/antioxidant markers, we evaluated the anti-inflammatory properties of valsartan. Valsartan suppressed cell-growth and impacted the anti-tumor-activities of 5-FU by apoptosis-induction. Valsartan inhibited the cells migration by perturbation of Matrix metalloproteinase (MMP1). Furthermore, valsartan inhibited tumor-growth and metastasis, and this was more notable in valsartan/5-FU combination-treated-group. The mechanism was plausible to be via the induction of Reactive-oxygen-species (ROS) and down-regulation of Superoxide-dismutase (SOD), thiol/catalase (CAT) as well as Vascular endothelial growth factor (VEGF) and Transforming growth factor beta (TGF-β). Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory components include fibronectin, Interleukin) IL-1β (, Tumor necrosis factor alpha) TNF-α (, Interferon gamma) INF-γ (, and Monocyte Chemotactic Protein 1 (MCP-1). Our findings demonstrated that targeting the AT1R receptor may inhibit tumor-growth and ameliorate fibrosis and inflammation associated with CRC via modulation of AT1 and TGF-β pathways.

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

In the realm of molecular science, intricate relationships between molecular structures and their biomedical and pharmacological characteristics have been revealed through empirical experiments. This exploration hinges on the application of numerical descriptors, known as Topological Indices, which illuminate the inherent properties of diverse molecular structures. With particular significance in the medical and pharmaceutical domains, these indices facilitate the prediction of biological features for new chemical compounds and drugs by quantifying weighted entropies. In the context of this paper, we delve into the concept of graph entropy, weaving it intricately with the topological properties of the crystalline framework of the copper oxide molecule, denoted as Cu\textsubscript{2}O$[i,j,t]$. Our primary objective is to unravel the mathematical symphony underlying the structural intricacies of Cu\textsubscript{2}O$[i,j,t]$ and to imbue it with the conceptual essence of entropy. We accomplish this through the computation of entropy, leveraging various topological indices, including weight. In addition to our analytical journey, we present a graphical comparison that juxtaposes the computed indices and entropies, shedding light on the interplay between mathematical analysis and the structural elegance of Cu\textsubscript{2}O$[i,j,t]$. This endeavor contributes to a deeper understanding of the material's multifaceted applications, spanning domains from chemical sensors to solar cells, photocatalysis, and batteries, where Cu\textsubscript{2}O's crystallographic structure plays a pivotal role.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Due to its application as an anti-cancer drug, pazopanib (1) has attracted the interest of many researchers and several studies on pazopanib synthesis have been reported over the years. This paper provides a novel route for synthesizing N,2,3-trimethyl-2H-indazol-6-amine (5) which is a crucial building block in the synthesis of pazopanib from 3-methyl-6-nitro-1H-indazole (6). By alternating between the reduction and two methylation steps compound 5 was obtained in comparable yield (55.0%) to what has been reported (54%). Noteworthy, the last step of N2-methylation also yielded N,N,2,3-tetramethyl-2H-indazol-6-amine (5’) as a new compound ever reported. Furthermore, the data presented in this paper can serve as instrumental for future research aimed at further refining the synthesis process of pazopanib.

The integration of Artificial Intelligence (AI) into education has the potential to revolutionize traditional teaching and learning methods. AI can offer personalized learning experiences, streamline administrative tasks, enhance feedback mechanisms, and provide robust data analysis. Numerous studies have demonstrated the positive impact of AI on both student outcomes and teacher efficiency. However, caution must be exercised when implementing AI in education, considering potential risks and ethical dilemmas. It is essential to use AI as a tool to support human educators rather than replace them entirely. The adoption of AI in education holds the promise of creating more inclusive and effective learning environments, catering to students of diverse backgrounds and abilities. As AI technology continues to advance, the education sector can anticipate even more innovative applications, further shaping the future of learning. This abstract provides an overview of the multifaceted landscape of AI in education, highlighting its potential benefits, associated challenges, and the importance of responsible integration.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of pulsatilla decoction (BEPD) of the traditional Chinese medicine herbal formula has been shown to be effective in treating UC. We aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL)1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. Our results showed that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduce the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

The plant Allium hookeri, belonging to the Allium genus, has a history of being used both as a common food ingredient and in herbal medicine. It has recently been reported to have anti-oxidant and anti-inflammatory effects. A. hookeri has been also shown to exhibit neuroprotective and anti-neuroinflammatory activities, but the active compounds responsible for these effects have not been identified in previous studies. This study aimed to perform a metabolite profiling using an HRESI-qTOF MS/MS-based molecular networking approach and identify the active compounds from A. hookeri that target senescent cell-associated secretory phenotype (SASP) inhibitory effects, which contribute to neuroprotective activities. As a result, ten compounds, including one new flavonoid (2) and nine known compounds (1 and 3–10), were identified, and their biological activity was tested. The most potent compound was N-trans-feruloyltyramine (7), which inhibited SASP markers and contributed to the senomorphic activities of A. hookeri. These findings suggest that the phenolamides from A. hookeri could be a promising source of bioactive compounds for preventing senescence-associated diseases.

Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.

Aberrant glycosylation affects cancer progression and immune evasion. Approximately 15% of colorectal cancers (CRCs) demonstrate microsatellite instability (MSI) and display major differences in outcomes and therapeutic responses as compared to corresponding microsatellite stable (MSS) tumors. We compared the N-glycan profiles of stage II and IV MSI CRC tumors, further subdivided into BRAFV600E wild-type and mutated subgroups (n=10 in each subgroup), with each other and with those of paired non-neoplastic mucosal samples using mass spectrometry. Further, the N-glycans of BRAFV600E wild-type stage II MSI tumors were compared to corresponding MSS tumors (n=9). Multiple differences in N-glycan profiles were identified between MSI CRCs and control tissues, as well as between stage II MSI and MSS samples. MSI CRC tumors showed a lower relative abundance of high-mannose N-glycans than the control tissues or the MSS CRCs. Among MSI CRC subgroups, acidic N-glycans showed tumor stage and BRAF mutation status dependent variation. Especially large, sulfated/phosphorylated, and putative terminal N-acetylhexosamine containing acidic N-glycans differed between the MSI CRC subgroups, showing opposite changes in stage II and IV, when comparing BRAF mutated and wild-type tumors. Our results show that molecular subgroups of CRC have characteristic glycan profiles that may explain certain carcinogenic properties of MSI tumors.

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.

High-quality rice (Oryza sativa L.) is increasingly widely planted in China with the improvement of people's living standards and the achievement of rice breeding efforts in recent years. However, the agronomic and physiological performances of high-quality indica rice (HQIR) under different nitrogen(N) application conditions in southern China are little known. Two-year consecutive field experiments were conducted with two HQIR and two ordinary-quality indica rice (OQIR) varieties under moderate and high N application rates, with yield and yield components, biomass, N up-take, and their related traits investigated. We found that grain yields of HQIR were slightly de-creased, but grain yields of OQIR were significantly increased by 6.60%-8.88% under high N rate compared with moderate N rate in both years. Thereby, OQIR produced 8.34%-11.87% and 22.00%-22.50% higher grain yield than HQIR under moderate and high N rates, respectively. The different responses of grain yield to N application rates were mainly due to decreased grain set-ting rate in HQIR and increased spikelets m-2 in OQIR under high N rate. Furthermore, high N rate significantly reduced pre-anthesis AE and improved grain-leaf area ratio, while did not in-crease post-anthesis DM compared with moderate N rate in HQIR, which might result in carbon metabolic deterioration and imbalance of source-sink relationship and subsequently lower supply of carbohydrate to panicle. Our results suggest that a moderate N rate (165 kg N ha-1) is beneficial for HQIR varieties to balance the maximum grain yield and high quality in southern China

Graphene-based nanomaterials have emerged as promising materials for a wide range of applications.. Therefore, in the last years carbon nanoparticles have attracted great attention due to their low toxicity, high biocompatibility and easy preparation. Recently, N-doped carbon nanoparticles have been shown to have improved antibacterial activity over the undoped nanomaterial, but it is difficult to find correlations between the structure of the nanoparticle and its antibacterial activity. With this purpose, here, we analyze the effect of both, the nanoparticle size and the surface chemical composition of four N-doped carbon nanoparticles on the growth of Escherichia coli bacteria. Our results were analyzed using a Ligand-Substrate model based on the Monod´s equation, which allows us to interpret the dependence of the nanoparticle-bacteria affinity with the nanomaterial structure.

Ketamine is a dissociative anesthetic and antidepressant with several biological targets. Among the many targets, ketamine, notably, has an antagonistic effect on molecular N-methyl-D-aspartate (NMDA) receptors and has been identified as a non-competitive inhibitor of these receptors. Although ketamine has a wide range of therapeutic uses in the clinical setting, it is often used recreationally due to its psychoactive and analgesic effects. Regardless of the indication, prenatal exposure to ketamine has been widely investigated. The misuse of this drug, particularly in pregnant women, has been a point of concern. The neurotoxic potential of ketamine positions it as a danger to a developing fetus. Furthermore, the ability of ketamine to cross the blood-placental barrier poses a threat to the health and maturation processes of the neonate. This paper reviewed published work that explores the mechanisms through which prenatal ketamine exposure can cause altered neurodevelopment, neurobehavior, and the physiological consequences that follow. By exploring investigations using multiple different subjects such as: rodents, non-human primates, and human subjects, this paper develops a full picture of the existing data to generate a strong foundation for improved and informed public health policies.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

In recent years, the role of non-coding RNAs (ncRNAs) in regulating cell physiology has begun to be better understood. Recent discoveries in viral molecular biology have revealed that such cellular functions are disturbed during viral infections mainly due to host cell ncRNAs, cellular factors, and virus-derived ncRNAs. Apart from the interplay between those molecules, other interactions derive from the specific folding of RNA virus genomes. These fulfill canonical regulation functions such as replication, translation, and viral packaging. In some cases, folds serve as precursors of small viral RNAs whose biogenesis is not yet clearly understood. Since ncRNAs and RNA viral genomes modulate complex molecular and cellular processes in viral infections, a new taxonomy is being proposed here overarching three main categories, considering the current information about ncRNA interactions in some well-known viral infections. The first category shows examples of host ncRNAs associated with the trigger of the immune response under viral infections. The second category describes interactions between the virus and host ncRNAs. The last category shows how the shape of the RNA viral genome is essential in processing RNAs derived from viruses. Finally, we introduce evidence of how these three categories can also work as a framework in order to organize known interactions of ncRNAs and cellular factors under DENV infection. This new taxonomy of interactions provides a comprehensive framework for organizing the ncRNA regulatory roles in the context of viral interactions and an RNA world.

The photocatalysis process over N-doped TiO2 under visible light is examined for Pb(II) oxidation to form the less toxic and handleable PbO2 suggesting a new method for Pb(II) remediation. The doping TiO2 with N element was conducted by simple hydrothermal technique and using urea as the N source with various concentrations. The doped photocatalysts were characterized by DRUVS, XRD, FTIR and SEM-EDX instruments. Photocatalysis of Pb(II) through batch experiment was performed for evaluation of the doped TiO2 activity under visible light, with applying various fractions of N doped, photocatalyst weigh, irradiation time, and solution pH. The research results attributed that N doping has been successfully performed, that shifted TiO2 absorption into visible region, allowing it to be active under visible irradiation. The photocatalytic removal of Pb(II) under visible ligth over N-TiO2 showed more effective than that of over the un-doped photocatalyst. The removal of Pb(II) has notably taken place through oxidation, that may form PbO2. The highest photocatalytic oxidation of Pb(II) 15 mg/L in 25 mL of the solution could be reached by using TiO2 doped with 10%w of N, 15 mg of N-TiO2 weight, 30 minutes of time, and at pH 8, suggesting a feseable method for Pb(II) remediation.

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of -amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus’s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase—an enzyme that is key in the biosynthesis of polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 μM at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 μM at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has caused the global pandemic as COVID-19, which is the most notorious global public health crisis in the last 100 years. SARS-CoV-2 is composed of four structural proteins and several non-structured proteins. The multi-facet nucleocapsid (N) protein is the major component of structural proteins of CoVs, However, there are no dedicated genomic, sequences and structural analyses focusing on potential roles of N protein. Hence, there is an urgent requirement of a detailed study on N protein of SARS-CoV-2. Herein, we are presenting a comprehensive study on N protein from SARS-CoV-2. We have identified seven motifs conserved in the three major domains namely N-terminal domain, linker regions and the C-terminal domains. Out of seven motifs, six motifs are conserved across different members of coronaviridae, while motif4 is specific for SARS CoVs with potential amyloidogenic properties. Additionally, we report this protein has large patches of disordered regions flanking with these seven motifs. These motifs are hubs of epitopes with 67 experimentally verified epitopes from related viruses. We report the presence of three nuclear localization signals (NLS1-NLS3 mapped to 36-41, 256-26, and 363-389 residues, respectively) and two nuclear export signals (NES1-NLS2 from 151-161 and 217-230 residues, respectively) in the N protein of SARS-CoV-2. These deciphered two Q-patches as Q-patch1 and Q-patch2, mapped in the regions of 266-306, and 361-418 residues, which potentially help in the aggregation of the viral proteins along with ²¹⁹LALLLLDR²²⁶ patch. Additionally, we have identified 14 antiviral drugs potentially binding to seven motifs of N-proteins using docking-based drug discovery methods.

A hydrothermal pretreatment of the microalga Nannochloropsis gaditana at mild temperatures has been studied in order to reduce N and O content in the biocrude obtained by hydrothermal liquefaction (HTL). The work is focused on the evaluation of temperature, reactor loading and time (factors) to maximize the yield of the pretreated biomass and the heteroatom contents transferred from the microalga biomass to the aqueous phase (responses). The study followed the factorial design and response surface methodology. An equation for every response has been obtained, which leads to the accurate calculation of the operating conditions required to obtain a given value of these responses. Temperature and time are critical factors with a negative effect on the pretreated biomass yield, but a positive one on the N and O recovery in the aqueous phase. The slurry concentration has to be low to increase heteroatom recovery and high to maximize the pretreated microalga yields

Digital Elevation Models (DEMs) are widely used in geographic and environmental studies. In the current work, the fusion of multi-source DEMs is investigated to improve the overall accuracy of public domain DEMs. Multi-scale decomposition is an important analytical method in data fusion. Three multi-scale decomposition methods – the wavelet transform (WT), bidimensional empirical mode decomposition (BEMD) and nonlinear adaptive multi-scale decomposition (N-AMD) - are applied to the 1-arc-second Shuttle Radar Topography Mission Global digital elevation model (SRTM-1 DEM) and the Advanced Land Observing Satellite World 3D – 30 m digital surface model (AW3D30 DSM) in China. Of these, the WT and BEMD are popular image fusion methods. A new approach for DEM fusion is developed using N-AMD (which is originally invented to remove the cycle from sunspots). Subsequently, a window-based rule is proposed for the fusion of corresponding frequency components obtained by these methods. Quantitative results show that N-AMD is more suitable for multi-scale fusion of multi-source DEMs, taking the ice cloud and land elevation satellite (ICESat) global land surface altimetry data as a reference. The vertical accuracy of the fused DEM shows significant improvements of 29.6% and 19.3% in a mountainous region and 27.4% and 15.5% in a low-relief region, compared to the SRTM-1 and AW3D30 respectively. Furthermore, a slope position-based linear regression method is developed to calibrate the fused DEM for different slope position classes, by investigating the distribution of the fused DEM error with topography. The results indicate that the accuracy of the DEM calibrated by this method is improved by 16% and 13.6%, compared to the fused DEM in the mountainous region and low-relief region respectively, proving that it is a practical and simple means of further increasing the accuracy of the fused DEM.

The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.

We explore the possibility of using the external regions of galaxy clusters to measure their mass accretion rate (MAR). The main goal is to provide a method to observationally investigate the growth of structures on the nonlinear scales of galaxy clusters. We derive the MAR by using the mass profile beyond the splashback radius, evaluating the mass of a spherical shell and the time it takes to fall in. The infall velocity of the shell is extracted from N-body simulations. The average MAR returned by our prescription in the redshift range z=[0, 2] is within 20-40% of the average MAR derived from the merger trees of dark matter haloes in the reference N-body simulations. Our result suggests that the external regions of galaxy clusters can be used to measure the mean MAR of a sample of clusters.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

In this paper, the P versus NP problem is studied based on a six-dimensional space-time perspective. The gap between the P-class and NP-class arises from the relationship between time and the solution, as well as the answer that is independent of time. The complexity of solving a problem depends on the time dependence of the answer. Solving problems whose answers do not depend on the passage of time is very difficult and impossible. Like the description of the gravitational factor in Newtonian physics, NP class problems require different mathematical tools. Based on the generalization of physical facts in mathematics, based on six-dimensional space-time, a method to solve problem P versus NP problem has been stated. The results of this study offer a fresh insight into information processing that occurs independent of the passage of time.

The correct selection of the value of p is a complex and iterative procedure that requires experience in the interpretation of the obtained interpolated maps. Inverse Distance Weighting is a method applied to the porosities of the K and L hydrocarbon reservoirs, discovered in the Neogene (Lower Pontian) subsurface sandstones in the northern Croatia (Pannonian Basin System). They represent small and large data samples. Also a standard statistical analysis of the data was made, followed by the qualitative-quantitative analysis of the maps, based on the selection of different values of the power distance exponent (p-value) for the K and L reservoirs maps. According to the qualitative analysis, for a small data set, p-value could be set on 1 or 2 giving the most optimal result, while for a large data set, a p value of 3 and 4 could be applied. By quantitative analysis, for the case of small data p=2 is recommended, resulting in a root mean square error value of 0.03458, a mean absolute error of 0.02013 and a median absolute deviation of 0.00546. Oppositely, a p-value of 3 and 4 is selected as appropriate for a large data set, with root mean square errors of 0.02435 and 0.02437, mean square errors of 0.01582 and 0.01509 and median absolute deviations 0.00896 and 0.00444. Eventually for a small data set, it is recommended to use a p-value of 2, and for a large data set, a p-value of 3 or 4.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption(PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6 % drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays re-vealed that the PC@MSNs were less toxic to aquatic life (LC50=257.867 mg/L) and that the formu-lation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's application scope in managing rice diseases.

Given a set of distinct non-negative integers X^n and a target certificate S in parametrized form: ∃X^k⊆X^n,∑_(x_i∈X^k)▒x_i =S (k=|X^k |,n=|X^n |). We present a polynomial solution of the subset sum problem with time complexity T≤O(kn)≤O(n^2) and space complexity S≤O(((n-1)n)/2)≤O(n^2 ), so that P = NP.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

The scope of this study was twofold: first, to introduce a new method in examining measurement invariance, especially with large-scale studies where a large number of group comparisons are involved: the alignment approach, where only configural invariance is necessary to achieve measurement invariance. Second, to evaluate the psychometric robustness of this approach using real-life data. Particularly, we applied this approach to examine whether the factor structure of a cognitive ability test (PGAT) exhibits measurement invariance across the 26 universities of the Kingdom of Saudi Arabia. The sample consisted of 9,849 graduate students from 26 universities around the Kingdom. The results indicated a robust configural model suggesting that the P-GAT subscales were invariant across the 26 universities. Finally, the aligned factor mean values were estimated, and factor mean comparisons of every group’s mean with all other group means were conducted for both cognitive domains (Verbal and Quantitative). In both domains, King Saud University had the highest mean score among all universities. Moreover, its mean factor score was significantly higher than any other university besides Dammam University. On the other hand, several universities allocated at the northern and Southern borders of the country exhibited the lowest factor mean scores.

Panax ginseng C. A. Meyer (P. ginseng), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and possesses a variety of pharmacological activities. Alzheimer's disease (AD) is neurodegenerative disease that creates a huge burden on the lives and health of individuals. In recent years, studies have indicated that the chemical components of P. ginseng, especially ginsenosides, play a pronounced positive role in the prevention and treatment of neurological diseases. This review aimed to summarize currently studies on chemical components and the mechanisms action in AD intervention treatment of P. ginseng, especially ginsenosides. In this review, the components of P. ginseng and their respective active effects were first introduced. Then the key molecular mechanisms and signaling pathways of P. ginseng were introduced, and its different active ingredients in the prevention and treatment of Alzheimer's disease-related pathogenesis were also summarized from the pathogenesis of AD Aβ generation and aggregation, hyperphosphorylation of tau protein，oxidant stress，neuroinflammation，mitochondrial damage，disorder of neurotransmitter and gut microbiota. Signaling pathway networks related to the action of ginseng active ingredients was constructed, which could serve as a therapeutic target for Alzheimer's disease. In addition to a detailed report on P. ginseng in improving Alzheimer's disease-related pathogenesis, the application of the current technology, spatial metabonomics in AD therapeutics and diagnostics were later discussed. Spatial metabonomics could be applied to investigate the multi-target intervention of P. ginseng on Alzheimer's disease. Research perspectives for the study of P. ginseng in the treatment of Alzheimer's disease were provided for further studies.

The research is a deep study of the CBOE Volatility Index (VIX), which represent the market sentiments of the S & P 500 Index (SPX) over a period of 33 years. It evaluates how the two indexes perform in the stock market crash and how reliable VIX is in predicting market sentiments. The research distributes the market rally in two forms, and one is a trust rally, when investors are happy to see the market in a stable form, and investors' sentiments are positive towards the stock market. Second is a fear rally, where investors' sentiments are negative, and their outlook is bearish for various reasons. It observes the pattern of rallies, like the longest trust or fear rally, in which year and its duration. The research analyzes data to reach a meaningful conclusion and various inferences that can be drawn from the study of historical data.

When 2−1/Q<p≤2, we establish the C^{0,1} and C^{1,α}-regularities of weak solutions to quasi-linear p-Laplacian type non-homogeneous equations in the Heisenberg group.

Paenibacilli are efficient producers of potent agents against bacterial and fungal pathogens, which are of great interest both for therapeutic applications in medicine as well as in agrobiotechnol-ogy. Lipopeptides produced by such organisms play a major role in their inactivation potential. In this work we investigated two lipopeptide complexes, the fusaricidins and the polymyxins, produced by Paenibacillus polymyxa strains DSM 32871 and M1 by MALDI-TOF mass spectrometry. The fusaricidins show potent antifungal activities and are distinguished by an unusual variabil-ity. For strain DSM 32871 we identified numerous yet unknown variants mass spectrometrically. DSM 32871 produces polymyxins of type E (colistins), while M1 forms polymyxins P. For both strains novel, but not yet completely characterized polymyxin species were detected, which pos-sibly are glycosylated. These compounds may be of interest therapeutically, because polymyxins attain increasing attention as last-resort antibiotics against multiresistant pathogenic Gram-negative bacteria. In addition, the volatilomes of DSM 32781 and M1 were investigated with a GC-MS approach using different cultivation media. Production of volatile organic com-pounds (VOCs) was strain and medium dependent. In particular, strain M1 manifested as an effi-cient VOC-producer that exhibited formation of 25 volatiles in total. A characteristic feature of Paenibacilli is the formation of volatile pyrazine derivatives.

The trace element selenium (Se) is taken up from the diet and becomes metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that Se status may serve as a useful prognostic marker for outcome in patients undergoing liver transplantation. Serum samples from patients were routinely collected before and after transplantation. Concentration of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, aetiology and pre-operative Child-Pugh and Model for End-Stage Liver Disease Scores. A total of 314 serum samples from 78 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent aetiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may thus support convalescence.

In developed countries, especially the big-sized ones like Australia and the USA, a car is almost an inevitable necessity to carry out daily activities. Due to this, used cars have become a great alternative to brand new cars because of their cost effectiveness. In this work, estimation of prices of used cars based on numerous factors is studied statistically. Data is based on prices of used cars sold across Australia. Statistical methods like correlation and permutation tests using linear regression model, exact tests and non-parametric bootstrapping is implemented to study the relationship of price with mileage and year of manufacture of the car using p-values and null hypothesis. Predictions are also made on the price by calculating a 95% confidence interval (CI) of median prices in small portions of the dataset. The study presents potential ideas for understanding correlation between variables and parameters in business studies.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. In this study, the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in liver were investigated. Rats were fed the diets with (0.54 %) or without EGCG supplementation for four weeks and were then intraperitoneally injected with acetaminophen (1g/kg). Results showed EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by increasing the Bax/Bcl2 ratio in liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen-glutathione and acetaminophen-protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in liver after acetaminophen treatment. Our results indicate that EGCG may lower oxidative stress and reduce the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in liver and thus lower hepatotoxicity

Copulas are useful tools for modeling the dependence structure between two or more variables. Copulas are becoming a quite flexible tool in modeling dependence among the components of a multivariate vector, in particular to predict losses in insurance and finance. In this article, we study the dependence structure of some well-known real life insurance data (with two components mainly) and subsequently identify the best bivariate copula to model such a scenario via VineCopula package in R. Associated structural properties of these bivariate copulas are also discussed.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

Graph coloring is a manifestation of graph partitioning, wherein, a graph is partitioned based on the adjacency of its elements. Partitioning serves potentially as a compartmentalization for any structural problem. Vertex coloring is the heart of the problem which is to find the chromatic number of a graph. The fact that there is no general efficient solution to this problem that may work unequivocally for all graphs opens up the realistic scope for combinatorial optimization algorithms to be invoked. The algorithmic complexity of graph coloring is non-deterministic in polynomial time (NP) and hard. To the best of our knowledge, there is no algorithm as yet that procures an exact solution of the chromatic number comprehensively for any and all graphs within the polynomial (P) time domain. However, several heuristics as well as some approximation algorithms have been attempted to obtain an approximate solution for the same. Here, we present a novel heuristic, namely, the 'trailing path', which returns an approximate solution of the chromatic number within polynomial time, and, with a better accuracy than most existing algorithms. The ‘trailing path’ algorithm is effectively a subtle combination of the search patterns of two existing heuristics (DSATUR and Largest First), and, operates along a trailing path of consecutively connected nodes (and thereby effectively maps to the problem of finding spanning tree(s) of the graph) during the entire course of coloring, where essentially lies both the novelty and the apt of the current approach. The study also suggests that the judicious implementation of randomness is one of the keys towards rendering an improved accuracy in such combinatorial optimization algorithms. Apart from the algorithmic attributes, essential properties of graph partitioning in random and different structured networks have also been surveyed, followed by a comparative study. The study reveals the remarkable stability and absorptive property of chromatic number across a wide array of graphs. Finally, a case study is presented to demonstrate the potential use of graph coloring in protein design – yet another hard problem in structural and evolutionary biology.

This paper includes some new investigations and results for post quantum calculus, denoted by (p,q)-calculus. A chain rule for (p,q)-derivative is developed. Also, a new (p,q)-analogue of the exponential function is introduced and some its properties including the addition property for (p,q)-exponential functions are investigated. Several useful results involving (p,q)-binomial coefficients and (p,q)-antiderivative are discovered. At the final part of this paper, (p,q)-analogue of some elementary functions including trigonometric functions and hyperbolic functions are considered and some properties and relations among them are analyzed extensively.

In this paper we establish several Hermite-Hadamard type integral inequalities for hyperbolic p-convex functions. Applications for special means are provided as well.

In this paper, we introduce a new generalization of the Hermite polynomials via (p, q)-exponential generating function and investigate several properties and relations for mentioned polynomials including derivative property, explicit formula, recurrence relation, integral representation. We also de…ne a (p, q)-analogue of the Bernstein polynomials and acquire their some formulas. We then provide some (p, q)-hyperbolic representations of the (p, q)-Bernstein polynomials. In addition, we obtain a correlation between (p, q)-Hermite polynomials and (p, q)-Bernstein polynomials.

In this study, a graphene-doped porous silicon (G-doped/p-Si) substrate for low ppm H₂ gas detection by an inexpensive synthesis route was proposed as a potential noble graphene-based gas sensor material and to understand the sensing mechanism. The G-doped/p-Si gas sensor was synthesized by a simple capillary force-assisted solution dropping method on p-Si substrates, whose porosity was generated through an electrochemical etching process. G-doped/p-Si was fabricated with various graphene concentrations and exploited as a H₂ sensor operated at room temperature. The sensing mechanism of the sensor with/without graphene decoration on p-Si was proposed to elucidate the synergetic gas sensing effect generated from the interface between the graphene and p-type silicon.

The current generation of nuclear reactors are evolutionary in design, mostly based on the technology originally designed to power submarines, and dominated by Light Water Reactors. The aims of the GenIV consortium are driven by sustainability, safety and reliability, economics, and proliferation resistance. The aims are extended here to encompass the ultimate and universal vision for strategic development of energy production, the ‘perpetuum mobile’ – at least as close as possible. We propose to rethink nuclear reactor design with the mission to develop a system which uses no fresh resources and produces no fresh waste during operation as well as generates power safe and reliably in economic way. The results of the innovative simulations presented here demonstrate that, from a theoretical perspective, it is feasible to fulfil the mission through the reuse of spent nuclear fuel from currently operating reactors as the fuel for a new reactor. The produced waste is less burdensome than current spent nuclear fuel which is used as feed to the system. However, safety, reliability and operational economics will need to be demonstrated to create the basis for the long term success of nuclear reactors as a major carbon free, sustainable, and applied highly reliable energy source.

An analysis of 1300+ existing ACE mutations revealed that 400+ are damaging and led us to hy-pothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer’s disease (AD) [Danilov, 2024]. Here we quantified blood ACE levels in EDTA-plasma from 41patients with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates. We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C and G325R are truly damaging and, likely, transport-deficient, with ACE levels in plasma only ~50% of controls. Another AD-associated ACE mutation, R1250Q, in the cytoplasmic tail, did not cause a decrease in ACE and, likely, did not affect surface ACE expression. We have also developed a method to identify patients with anti-catalytic mutations in the N domain. These mutations may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD. Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has potential to identify individuals at an increased risk of late-onset AD. These individuals may benefit from future preventive or therapeutic interventions involving a combination of chemical and pharmacological chaperones, as well as proteasome inhibitors, aiming to enhance ACE protein traffic. This approach has been previously demonstrated in a cell model of the transport-deficient ACE mutation, Q1069R [Danilov, 2010].

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

Obesity and overweight are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia, which are closely related to a sedentary lifestyle and lack of exercise. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and decreases the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.0±1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) decreased by approximately 15% (p=0.022), 12.7% (p=0.008), 33% (p=0.006), 11% (p<0.046), and 13% (p=0.007), respectively. In the serum lipid profile, at week 12, they showed a remarkable decrease in the total cholesterol (TC) and triglyceride (TG) levels, up to 17% (p<0.019) and 54% (p<0.002) from the baseline, respectively. Although the serum HDL-C was increased by approximately +12% from the baseline, the percentage of HDL-C in TC, HDL-C/TC (%), was increased by up to +32% (p=0.007) at week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold in all participants at week 12 from the baseline. In particular, the male participants showed a 1.4-fold increase (p=0.027) from the baseline. The larger increase in serum CoQ10 was correlated with the larger increase in the serum HDL-C during 12 weeks. The hepatic function parameters were improved; the serum -glutamyl transferase decreased at week 12 by up to 55% (p<0.007), while the aspartate aminotransferase and alanine transaminase levels decreased within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly in VLDL and LDL, with a remarkable decrease in the TG content in particles. The antioxidant abilities of HDL2 and HDL3, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold (p<0.001) and 1.6-fold (p<0.001) at week 12. The particle size and number of HDL2 were increased up to +10% during the 12 weeks with a remarkable decrease in the TG content, glycation extent, oxidation up to 32% (p=0.032), 18% (p=0.043), and 11% (p=0.023), respectively. The particle number and diameter of HDL3 were increased by up to +9% with a remarkable increase in the PON activity, FRA activity, and TC content of +82% (p<0.001), +56% (p<0.001), and +32% (p=0.009), respectively. Expression of apolipoproteinA-I in HDL2 and HDL3 were significantly elevated more in both gender around 30~48% with more distinct band intensity and less glycation at week 12. These improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos. Under the co-presence of carboxymethyllysine (CML), a microinjection of HDL2 to zebrafish embryo from week 0 resulted in approximately 47% survivability with developmental defects and attenuated speed. On the other hand, the HDL2 microinjection from week 12 resulted in remarkably higher survivability (~ 70%). In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise showed significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment. At week 12, all participants showed a remarkable decrease in oxidation and glycation extent in the VLDL and LDL with a decrease in the TC and TG content. Significant enhancement of the qualities and functionalities in HDL2 and HDL3 by the policosanol consumption were also detected: increase in apoA-I content, TC content, particle size, and particle numbers along with antioxidant abilities, such as PON and FRA.

The intensive care unit is characterized by the critical care of the infants and children who access it, as well as the high complexity of care. This implies and requires optimal integration among the various professionals working there and their ability to work as a team. The purpose of the study was to describe how nurses perceive clinical risk and how they relate to it and to identify adverse events and related risk factors. Nine nurses, two moderators and one external observer partici-pated in the focus group. In the qualitative analysis, 9 themes describing the perception of clinical risk in PICU were identified, including teamwork, specific training, time management, team communication, management, individual errors, structural criticality, patient fac-tors/characteristics, and standardization. Safety culture can be fostered by hospital management to involve PICU nurses in promoting patient safety, which could improve breaking down barriers that prevent nurses from fulfilling their roles.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.