The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

The use of thiosemicarbazones (TSCs) as ligands for the functionalization of nanoparticles (NP) for various purposes, such as the covalent immobilization is fueled by their modular character (thiosemicarbazides + carbonyl compound), allowing enormously broad variation of up to four substituents on the main R1R2C=N(1)–NH–C(S)–N(4)R3R4 core. For R1 and R2 we introduced di-2-pyridyl ketone for the coordination of metals and 9-anthraldehyde for luminescence. R3 and R4 substituents were varied for various purposes. Amino acids were functionalized at the N4 position to [R1R2TSC–spacer–amino acid] conjugates for future peptide conjugation or for direct anchoring to NP via their carboxylic function. Further direct NP anchoring functions such as phosphonic acid (OP(OH)2), glucose, o-hydroquinone, OH, and thiol (SH) were introduced with or without separation through hydrocarbon spacer units such as phenyl, cyclohexyl, benzyl, ethyl and methyl in [R1R2TSC–spacer–anchor group] conjugates. [R1R2TSC–spacer–end group] conjugates including OH, S-Bn (Bn = benzyl), NH-Boc (Boc = tert-butyloxycarbonyl), COOtBu, or N3 end groups were produced for the facile formation of amide, ester, or triazine conjugates through click chemistry. The synthesis of the thiosemicarbazides H2NH–C(S)–NR3R4 starting from amines, including amino acids, SCCl2 or CS2, and hydrazine and their condensation with dipyridyl ketone and anthraldehyde lead finally to 34 new TSC derivatives. They were synthesized in up to six steps with overall yields ranging from 10 to 85% and were characterized by a combination of elemental analyses, mass spectrometry, and magnetic nuclear resonance spectroscopy. UV-vis absorption and photoluminescence spectroscopy allowed to easily trace the dipyridyl imine and anthracene chromophores.

Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop highly efficient and low toxic ACM formulation, we propose to prepare ACM CAM, with basic amino acids (lysine, arginine and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAMs were characterized by polarizing light microscopy, differential scanning calorimetry and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAMs were evaluated in a rat gastric ulcer model. The results demonstrated CAMs improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAMs are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug-amino acid CAMs.

Biotechnological potential of Thermoanaerobacter strain AK15 to produce ethanol and valuable alcohols from carbohydrates and amino acids were evaluated in present study. The strain is highly ethanologenic, producing a maximum of 1.57 mol ethanol per mol of glucose degraded at high liquid-gas phase ratios. The strain degrades most of the sugars tested as well as starch and pretreated hydrolysates of biopolymers (Whatman paper, newspaper, Timothy grass, Rhubarb leaves, and several macroalgae species) to ethanol mainly. The strains degraded serine and threonine when used as a single substrate, producing mainly acetate and ethanol as end products, and the branched-chain amino acids (leucine, isoleucine, valine) when cultivated in the presence of thiosulfate. The main end products from branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. Finally, the strain was also shown to use butyrate as an electron sink during glucose degradation resulting in the reduced product butanol in addition to end products produced from glucose. Thus, strain AK15 is a promising candidate for ethanol and fine chemical production from a range of lignocellulosic and algal biomass.

Serine peptidase CLPP is conserved among bacteria, chloroplasts, and mitochondria. In humans and mice, its loss causes Perrault syndrome with growth deficit, infertility, deafness, and ataxia. In the filamentous fungus Podospora anserina, CLPP-loss leads to longevity. CLPP substrates are selected by CLPX, an AAA+ unfoldase. CLPX is known to target delta-amino-levulinic-acid synthase (ALAS) to promote pyridoxal-phosphate (PLP) binding. CLPX may influence cofactor association with other enzymes. Here, the evaluation of P. anserina metabolomics highlighted arginine/histidine reduction. In Mus musculus cerebellum, reductions of Arginine/Histidine and Citrulline occurred with concomitant accumulation of heme-precursor protoporphyrin-IX. This suggests that increased biosynthesis of 5-carbon (C5) chain deltaALA consumes not only C4 succinyl-CoA with C1 glycine but also specific C5 delta amino-acids. As responsible enzymes for these converse effects, elevated abundance of CLPX and ALAS is paralleled by elevation of OAT (PLP-dependent, ornithine-delta-aminotransferase). Possibly as consequence of altered C1 metabolism, CLPP-null cells in P. anserina proteome profiles showed strong accumulation of a methyltransferase and two mitoribosomal large subunit factors. Reduced Histidine levels may explain previously observed metal interaction problems. As main nitrogen-storing metabolite, deficient Arginine would affect the urea cycle and polyamine synthesis. Supplementation of Arginine and Histidine might rescue growth deficits of CLPP-mutant patients.

Peach (L.) is a kind of fruit tree with considerable economic and nutritional significance. However, it shows a high sensitivity to drought stress, which has a profound impact on its growth. L-methionine (MET) and L-proline (PRO) are two amino acids synthesized by plants, which play an important role in abiotic stress response. However, their exact mechanism of action remains elusive. Through physiological analysis, MET (500ppm) and PRO (500ppm) treatments can effectively reduce the adverse effects of drought stress on the growth of peach seedlings. The results show that MET and PRO can effectively inhibit the stomatal opening of plant leaves under drought conditions and reduce the water evaporation of leaves under drought conditions. In addition, the application of MET or PRO promoted the accumulation of carbohydrates in the leaf tissues of peach seedlings under drought conditions, increased the intracellular relative water content (24%, 24%), decreased the leaf electrical conductivity (21%, 24%), and alleviated the membrane damage caused by drought. Experimental studies have confirmed that the alleviation of drought stress is due to the removal of reactive oxygen species (ROS) in vivo, that is, the downregulation of malondialdehyde (18%, 19%)，peroxidase (50%, 5%) and superoxide dismutase (12%, 14%) activities. In addition, the application of exogenous amino acids also improved the root morphological structure and root vitality of peach seedlings，which was conducive to absorbing external buffer substances and alleviating drought stress. In summary, the application of exogenous amino acids can effectively alleviate the effects of drought stress on plants and reduce the harm.

Organic Medium Enclosed Trough (OMET) is a new non-drainable growing technique. The study envisioned to investigate the interactive effects of OMET and Amaranth species vari-ation on some growth attributes, bioactive compounds and nutrients. Three Amaranth species: A. caudatus, A. cruentus and A. tricolor were grown in an OMET and non-OMET growing conditions. Growth attributes, irrigation water, bioactive compounds and nutri-ents were determined. Non-OMET and A. cruentus showed the highest total phenolics and flavonols followed by A. caudatus and A. tricolor, whilst tannins were predominant in A. caudatus followed by A. cruentus and A. tricolor. The use of unsupervised PCA showed major metabolic variation based on Amaranth species and the use of supervised OPLS-DA showed clear metabolic variation based on OMET and non-OMET. OMET and A. cruentus showed the highest plant height, stem diameter, biomass, and some nutrients (%protein, Ca, P, Cu, Se, Zn), followed by A. caudatus based only on growth and biomass, and A. tricol-or based only on some nutrients (Mg, K, Mn, and Fe). The use OMET system on A. cruentus and A. tricolor can be recommended to mitigate climate change effects on nutritional com-position using low irrigation water.

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.

Wheat and corn silages are widely used as ruminant feed in Israel due to their availability and cost-effectiveness. To ensure long-term preservation without compromising nutritional quality, effective methods must be employed. Inclusion of additives during harvest and ensiling can enhance efficiency and address preservation challenges. In the current study, the effects of microbial inoculum (MI) and urea on the chemical composition, amino acid profiles, aerobic stability, and in vitro digestibility of wheat and corn silages were investigated. Samples of wheat and corn were subjected to four treatments: control, MI, Urea, and a combination of MI+Urea. The treatments were ensiled in anaerobic conditions and opened after 1, 7, 14, or 28 days. Results showed that additives improved the quality parameters of wheat and corn silages. The inclusion of MI produced the most aerobically stable silages. The inclusion of urea in silages deteriorated aerobic stability. Additives improved in vitro cell wall carbohydrates digestibility in both silages and was the best when MI was combined with urea. These results imply additives could be incorporated in silages to enhance their nutritional value, aerobic stability and digestibility. Nonetheless, increased CP content with additives was not accompanied with parallel increase in amino acids content in corn silage.

Bean common mosaic virus from the genus Potyvirus has a wide range of hosts and a very negative impact on cultivated crops from the genus Phaseolus. The risk of viral infection of economically important crops increases even if the carriers of the virus are related plant species growing on agroecological interfaces. Such plant species have emerged as new hosts for BCMV, usually harboring novel genetic variants of the virus. A novel genetic variant of BCMV was isolated from a symptomatic crownvetch plant, where the presence of this virus was confirmed by Western-blotting analysis and by amino acid identities in peptide fragments of CI, HC-pro, and CP proteins using the nanoLC-ESI-Q-TOF. The novel BCMV SVK isolate differed from the most genetically similar one in 0.91% of nucleotides and 1.55% of amino acids. The highest number of amino acid substitutions (8.8% of amino acids) was in the P1 protein, followed by CP (2.44% of amino acids). Minor substitutions were in Hc-pro, CI, and Nib proteins. The symptomatic crownvetch plant was confirmed as a new host and carrier of the novel BCMV isolate.

Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.

Genetic code expansion has emerged as an enabling tool to provide insight into functions of understudied proteinogenic species such as small proteins and peptides, and to probe protein biophysics in the cellular context. Here we discuss recent technical advances and applications of genetic code expansion in cellular imaging of complex mammalian protein species, along with considerations and challenges upon using the method.

The article describes synthesis of aminoorgano-functionalized silica as a perspective material for catalysis application. The amino groups have electron donor properties valuable for metal chemical state of palladium. So presence of electron donor groups is important for increasing of catalysts stability. The research is devoted to investigation of silica amino-modified support influence on activity and stability of palladium species in 4-nitroaniline hydrogenation process. A series of catalysts with different supports such as SiO2, SiO2-C3H6-NH2 (amino-functionalized silica), γ-Al2O3 and activated carbon were studied. The catalytic activity was studied in the hydrogenation of 4-nitroaniline to 1,4-phenylenediamine. The catalysts were characterized by scanning electron microscopy, transmission electron microscopy, x-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and pulse chemisorption of hydrogen. The 5 wt. % Pd/SiO2-C3H6-NH2 catalyst exhibited the highest catalytic activity for 4-nitroaniline hydrogenation with 100% conversion and 99% selectivity with respect to 1,4-phenylenediamine.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

The sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys, and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced a marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased the survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53 -/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Recently, methods to detect DoS and spoofing attacks that occur on in-vehicle networks using CAN Protocol are being studied through deep learning models such as CNN, RNN, and LSTM. These studies have produced significant results in the field of In-Vehicle Network attack detection using deep learning models. In addition, significant results are being achieved through research on applying time series-based deep learning models such as LSTM to detect DoS attacks and replay attacks occurring in in-drone networks by expanding them to drones using the UAVCAN protocol. In this paper, we conducted an experiment to detect in-drone network attacks through non-time series analysis using machine learning models and deep learning models, and through appropriate learning for each attack type, it can also be analyzed through non-time series analysis. The results showed that it was possible to detect attacks.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

The 14-3-3 protein in dimorphic fungi from the Ajellomycetaceae family, including Blastomyces spp., Histoplasma spp., Paracoccidioides spp., Emergomyces spp., and Emmonsia spp., play a crucial role in host-pathogen interactions. Thus, we performed a comparative genomic analysis across 21 fungal species which revealed the presence of two 14-3-3 gene copies in most fungi, with exceptions in Histoplasma ohiense and Emergomyces africanus which revealed one and three gene copies, respectively. Moreover, in this study it was found a high degree of similarity (over 70%) between fungal 14-3-3 proteins and the human 14-3-3ɛ isoform, particularly in conserved Ser/Thr phosphorylation sites. However, distinct differences were noted in the C- and N-terminal regions, where fungal 14-3-3 proteins have additional amino acids. Though not directly linked to pathogenicity, these structural differences may offer insights into new therapeutic strategies. The conserved regions and 3D similarities identified could serve as potential targets for broad-spectrum antifungal drug development and vaccine production. Further research is necessary to validate these in silico findings and explore the functional roles of these phosphorylation sites, which could contribute to understanding fungal pathogenicity and developing specific antifungal interventions.

Despite the technological advancements of 3-D city models, the 3-D shape abstraction methods for urban vegetation are recent and still limited to support spatial analysis of individual or groups of trees and forest patches. In this paper, a scheme for individual urban tree abstraction, which retains the semantic complexity of the object, is proposed. Our contribution is three-fold. First, an initial tree structure based on a new 3-D aggregation operator is proposed. Second, we developed Gestalt rules for 3-D urban vegetation mapping. Third, current state-of-the-art deep learning is adapted for the abstraction of individual urban trees. Quantitative and qualitative results show the effectiveness of our proposed approach in accurately reducing the spatial density of trees and the degree of fragmentation of the total green area, which can access information about the location, size, and spatial distribution of mapped urban trees.

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production. To explore this, 1909 skin isolates, mainly from the genera Staphylococcus, Bacillus, and Corynebacterium, were tested for NT production. Only 6.7% of the isolates were capable of producing NTs, all of which belonged to the Staphylococcus genus. Based on substrate specificity, we identified two distinct profiles among the NT producers. One group primarily produced tryptamine (TRY) and phenylethylamine (PEA), while the other mainly produced tyramine (TYM) and dopamine (Dopa). These differing production profiles could be attributed to the activity of two distinct aromatic amino acid decarboxylase enzymes, SadA and TDC, responsible for generating the TRY/PEA and TYM/Dopa product spectra, respectively. SadA and TDC orthologues differ in structure and size; SadA has approximately 475 amino acids, whereas the TDC-type consists of about 620 amino acids. The genomic localization of the respective genes also varies: tdc genes are typically found in small, conserved gene clusters, while sadA genes are not. Heterologous expression of sadA and tdc in Escherichia coli yielded the same product spectrum as the parent strains. The possible effects of skin microbiota-derived NTs on neuroreceptor signaling in the human host remain to be investigated.

The reaction of 2-((diphenylmethylene)amino)acetonitrile with (E)-1-phenyl-3-(thiophen-2-yl)prop-2-en-1-one was performed by using 33% NaOH in CH3CN for 30 min at 0°C. The main product - rel-(2R,3S)-2-((diphenylmethylene)amino)-5-oxo-5-phenyl-3-(thiophen-2-yl)pentanenitrile was isolated and characterized by IR, 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS).

Purpose. This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and growth of organisms. Methods and Results. We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy, in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. Conclusion. A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.

Glioblastoma is a highly malignant brain tumor consisting of heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in single run, those may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even the both types of glioblastoma cells share several common metabolic aspects, they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites - polaromics.

Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from ovarian removal or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusions: This study, for the first time, depicted the metabolic profile of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by estrogen deprivation.

Chiral interactions play a crucial role in both chemistry and biology. Understanding the behavior of chiral molecules and their interactions with other molecules is essential, and chiral interactions in solutions are particularly important for studying chiral compounds. Chirality influences the physical and chemical properties of molecules, including solubility, reactivity, and biological activity. In this work, we used Isothermal Titration Calorimetry (ITC), a powerful technique for studying molecular interactions, including chiral interactions in solutions. We conducted a series of ITC measurements to investigate the heat of dilution and the heat of racemization of several amino acids (Asn, His, Ser, Ala, Met, and Phe). We also performed ITC measurements under different solute concentrations and temperatures to examine the effects of these parameters on chiral interactions, as well as the heat of dilution and racemization. The results of our measurements indicated that the heat of dilution, specifically the interactions between the solvent (water) and solute (chiral molecules), had a significant impact compared to the chiral interactions in the solution, which were found to be negligible. This suggests that the interactions between chiral molecules and the solvent play a more dominant role in determining the overall behavior and properties of the system. By studying chiral interactions in solutions, we can gain valuable insights into the behavior of chiral compounds, which can have implications in various fields, including drug design, chemical synthesis, and biological processes.

With the extension of the post-catch circulation time, a series of changes had taken place in the soft tissue of the live clams, resulting in the decline of its quality. This study investigated the quality changes of clams (Ruditapes philippinarum) in cold chain and was mainly focused on the rehydration process, which included gradient heating rehydration (GR) and sudden heating rehydration (SR). It was found that the GR had a better effect on the quality of clams than the SR. The GR stage clams showed a higher survival rate, glycogen content and adenylate energy charge (A.E.C) value than the SR stage clams. Conversely, the GR stage clams showed lower lactic acid content and K-value than the SR stage clams. The results indicated that the gradient heating rehydration was beneficial to the quality of clams. The transportation and rehydration strategies benefited both producers and shellfish merchants to save total cost.

This research evaluates the inhibitory effect of L-amino acids (AAs) with different side chain lengths on Fe surface implementing Monte Carlo (MC) simulation. A quantitative and qualitative description of the adsorption behavior of AAs on the iron surface has been carried out. Calculations have shown that the absolute values of the adsorption energy of L-amino acids increase with side chain prolongation; they are also determined by the presence of heteroatoms. AAs from nonpolar and basic groups have the best adsorption ability to the iron surface, which indicates their highest inhibitory efficiency according to the results of MC simulation.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

IntroductionGlycogen synthase kinase 3 (GSK-3) has been associated with a lot of diseases, such as Alzheimer’s Disease and diabetes. Its role in depression is connected to stress and neuroinflammation. Lithium is an essential inhibitor of GSK-3. Some studies have suggested that the use of this psychiatric medication may lower suicide rates. Here, we outline the current understanding and discoveries regarding the link between GSK-3 and suicide. MethodWe used the PRISMA statement and defined the PECOS strategy, such as Population (P) = individuals; exposure (E) = GSK-3 alteration function; comparison (C) = without GSK-3 alteration function; outcome (O) = suicide; and study design(S) = all kinds of studies with an association between GSK-3 and suicide.ResultsTwelve studies were included in this review. GSK-3 appears to be related to suicidal behavior by activating inflammatory pathways, activating genes, altering neurotransmission, and increasing impulsivity. Clinical studies do not present robust results that allow defining an epidemiological profile of greater risk for suicidal behavior in association with changes in the functioning of GSK-3.ConclusionThe interference of GSK-3 functioning in suicidal behavior seems inevitable, with solid evidence from laboratory animal studies. However, there is a need for further clinical studies on this crucial topic to answer better some questions about the association between GSK-3 and suicide.

Applications for Wireless Sensor Networks (WSNs) range from monitoring the environment to automating factories. However, sustained and effective functioning is made more difficult by Sensor Nodes (SNs) limited energy supplies in which optimization is the main issue. So with the aim of increasing the lifespan by decreasing the energy consumption of WSN, Low-Energy Adaptive Clustering Hierarchy (LEACH) protocol with Deep Learning (DL) algorithm is analyzed in this paper. LEACH is a hierarchical mechanism that elects Cluster Heads (CHs) and regularly rotates their positions in order to allocate energy use effectively by using the same amount of energy. However, Deep Learning (DL) method is used to further improve energy optimization. In many applications, the types of Deep Learning methods like Artificial Neural Networks (ANNs) have shown to be very useful. Using this method, WSNs may make more efficient decisions that reduce energy consumption. Data aggregation, duty cycling, and transmission protocols may all be optimized by Deep Learning model's ability to recognize patterns and forecast network behavior. This results in lower energy consumption, a longer lifespan for the network, and better overall performance.

Nowadays, technological advancement has transformed traditional vehicles into Au-tonomous Vehicles (A.V.s). In addition, in our daily lives, A.V.s play an important role since they are considered an essential component of smart cities. A.V. is an intelligent vehicle capable of main-taining safe driving by avoiding crashes caused by drivers. Unlike traditional vehicles, which are fully controlled and operated by humans, A.V.s collect information about the outside environment using sensors to ensure safe navigation. Furthermore, A.V.s reduce environmental impact because they usually use electricity to operate instead of fossil fuel, thus decreasing the greenhouse gasses. However, A.V.s could be threatened by cyberattacks, posing risks to human life. For example, re-searchers reported that Wi-Fi technology could be vulnerable to cyberattacks through Tesla and BMW AVs. Therefore, more research is needed to detect cyberattacks targeting the components of A.V.s to mitigate their negative consequences. This research will contribute to the security of A.V.s by detecting cyberattacks at the early stages. First, we inject False Data Injection (FDI) attacks into an A.V. simulation-based system developed by MathWorks. Inc. Second, we collect the dataset generated from the simulation model after integrating the cyberattack. Third, we implement an intelligent symmetrical anomaly detection method to identify FDI attacks targeting the control system of the A.V. through a compromised sensor. We use long short-term memory (LSTM) deep networks to detect FDI attacks in the early stage to ensure the stability of the operation of A.V.s. Our method classifies the collected dataset into two classifications: normal and anomaly data. The ex-perimental result shows that our proposed model's accuracy is 99.95%. To this end, the proposed model outperforms other state-of-the-art models in the same study area.

L-(+)-Furanomycin 1 is a miniature antibacterial natural product that contains an -amino acid core. This non-proteinogenic α-amino acid was first isolated in 1967 by Katagiri and co-workers from the fermentation broth of Streptomyces threomyceticus L-803 (ATCC 15795). It is a substrate of isoleucyl aminoacyl tRNA synthetase that replaces isoleucine in the protein translation process and exhibits antibacterial properties in vitro. It effectively acts as an antibacterial agent against M. tuberculosis, E. coli, B. subtilis, and some Shigella and Salmonella bacterial species at concentrations as low as the micromolar range. Consequently, synthetic chemists have garnered considerable interest from their specific structure-activity profile, distinctive chemical compositions, and distinct biological profile. This review comprehensively describes cutting-edge synthetic methodologies for synthesizing furanomycin and its analogs reported to date. Therefore, this review will offer an initial perspective on synthesizing furanomycin and its customized compounds.

The decline in global pollinator populations has raised serious concerns about the sustainability of ecosystems and agricultural productivity. Urban environments, often characterized by habitat loss and environmental stressors, are considered challenging habitats for pollinators. However, urban green spaces, including street and ornamental trees, can play a crucial role in supporting pollinators by providing essential food resources. This study aimed to evaluate the sugar and amino acid production of eight urban tree species to determine their potential contributions to pollinator nutrition. Our findings revealed significant variability among species regarding nectar volume, sugar content, and amino acid composition, emphasizing the importance of considering multiple factors when assessing the utility of floral resources. Consequently, Tilia amurensis, Heptacodium miconioides, Aesculus turbinata, and Wisteria floribunda demonstrated superior potential in supporting urban pollinator communities. Contrastingly, Sorbus commixta, Styrax japonicus, and Cornus kousa, often favored for their aesthetic appeal, showed less potential. This study underscores the need for urban tree selection that prioritizes species that provide diverse and abundant nutritional resources for pollinators while balancing aesthetic and ecological values. Our results offer a foundation for better-informed urban biodiversity management and contribute to creating pollinator-friendly urban environments.

Dietary protein quality plays a key role in maintaining intestinal mucosal integrity, but also modulates the growth of luminal microorganisms. This work assessed the effect of dietary protein sources on the performance, gut morphology, and microbiome in Nile tilapia. Four isonitrogenous and isolipidic diets comprising equivalent amounts of the protein supply derived from either PLANT, ANIMAL, INSECT, or MICROBIAL (bacterial biomass) sources were fed to triplicate groups of fish (IBW: 12 g) during 46 days. Fish fed ANIMAL and MICROBIAL diets showed significantly higher growth than those fed the PLANT and INSECT diets (P < 0.05). Relative abundance at the phylum level shows Bacteroidetes, Fusobacteria and Proteobacteria as more abundant phyla in tilapia’s intestine, while Cetobacterium is the most representative genera in all treatments. Interesting patterns were observed in the correlation between amino acid intake and genus and species abundance. Metabolism prediction analysis showed that microbial amine and polyamine degradation pathways are modulated depending on diets. In conclusion, different protein sources interfere directly with the cross-talk of bacteria pathways and amino acid intake.

As the COVID-19 pandemic progresses, new variants of SARS-CoV-2 continue to emerge. This underscores the need to develop optimized tools to study such variants, as well as new coronaviruses that may arise in the future, and to use them for antiviral drug development. Here we introduce microscale thermophoresis (MST) as a reliable and versatile tool for coronavirus research, which we demonstrate through three different applications described in this report: 1) binding of the SARS-CoV-2 spike receptor binding domain (RBD) to peptides as a strategy to prevent virus entry, 2) binding of the RBD to the viral receptor ACE2, and 3) binding of the RBD to ACE2 in complex with the amino acid transporter SLC6A20/SIT1 or its allelic variant rs61731475 (p.Ile529Val). Our results demonstrate that MST is a highly precise approach to study protein-protein and/or protein-ligand interactions in coronavirus research, making it an ideal tool for studying viral variants and developing antiviral agents. The ability to measure interactions with proteins in their near-native plasma membrane environment is a unique advantage of the MST assay over other available binding assays.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.

Carvacrol has long been studied for its natural antifungal potential and food preservative. But the exact mode of its action remained highly complex as a general, but especially for Penicillium digitatum (P. digitatum) largely remained unexplored. Herein, a 1H-NMR-based metabolomic technique was used to investigate the antifungal mechanism of carvacrol. The metabolomic profiling data showed that alanine, aspartate, glutamate and glutathione metabolism were imbalanced in the fungal hyphae. A strong positive correlation was seen between aspartate, glutamate, alanine and glutamine, while negative correlation among glutathione and lactate. These metabolic changes revealed that carvacrol-induced oxidative stress had disturbed the energy production and amino acid metabolism of P. digitatum. Current study will improve the understanding of the metabolic changes posed by plant-based fungicides in order to control citrus fruit green mold caused by P. digitatum. Moreover, the study will provided certain experimental and theoretical basis for the development of novel citrus fruit preservatives.

β-hydroxy β-methylbutyrate (HMB) is a bioactive metabolite formed from breakdown of the branched-chain amino acid leucine. Given the popularity of HMB supplements among different athletes, specifically, those who engage in regular resistance training, this review was performed to summarize current literature on some aspects of HMB supplementation that have received less attention. Because of the small number of published studies, it has not been possible to conclude the exact effects of HMB on cardiovascular parameters, oxidative stress and inflammatory markers. Thus, the interpretation of outcomes should be taken cautiously. However, the data presented here suggest that acute HMB supplementation may attenuate pro-inflammatory response following an intense resistance exercise in athletes. Also, the available findings collectively indicate that chronic HMB consumption in conjunction with resistance training has no more adaptive advantages associated with decreasing cardiovascular risk factors and oxidative stress markers. Taken together, there is clearly a need for further well-designed, longer duration studies to support these findings and determine whether HMB supplementation affects the adaptations induced by resistance training associated with body’s inflammatory condition, antioxidative defense system, and cardiovascular risk factors in humans.

Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress can affect neurogenesis is through alterations of the kynurenine (KYN) pathway, which is activated under stress. Meanwhile, n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation has anti-inflammatory properties and may enhance stress resilience. Whether n-3 PUFA alters stress responsivity KYN is unknown. This placebo-controlled trial examined the effect of n-3 PUFA on KYN metabolism, inflammation, depressive symptoms and mood; and stress-induced changes following a laboratory stressor. Using a placebo-controlled design, 47 healthy male adults were received 4g/d of Omega-3, or a placebo for 12 weeks. A significant group-by-time interaction was found for inflammation markers - gp130 (F= 7.07, p = 0.011), IL-6R alpha (F= 10.33, p = 0.003), and TNF_RI (F= 10.92, p = 0.002). No significant group-by-time interactions were found for mood or depressive symptoms, except for Hedonic Tone (F= 6.50, p = 0.014), neither for KYN metabolites and stress-induced changes to the KYN metabolites and mood following a laboratory stressor. Overall, elevating n-3 PUFAs levels in healthy males ameliorates inflammatory markers but does not ameliorate KYN metabolism, depressive symptoms, mood, or stress responsivity KYN metabolism and mood. The study was registered at ClinicalTrials.gov with identifier NCT05520437 (30/08/2022 first trial registration).

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

For Interferometry Synthetic Aperture Radar (InSAR), the normal baseline is one of the main factors that affect the accuracy of the ground elevation. For Gaofen-3 (GF-3) InSAR processing, the poor accuracy of the real-time orbit determination resulting in a large baseline error, leads to the modulation error in azimuth and the slope error in range for timely Digital Elevation Model (DEM) generation. In order to address this problem, a baseline estimation method based on external DEM is proposed in this paper. Firstly, according to the characteristic of the real-time orbit of GF-3 images, orbit fitting is executed to remove the non-linear error factor. Secondly, the height errors are obtained in slant-range plane between Shuttle Radar Topography Mission (SRTM) DEM and the GF-3 generated DEM after orbit fitting. At the same time, the height errors are used to estimate the baseline error which has a linear variation. In this way, the orbit error can be calibrated by the estimated baseline error. Finally, DEM generation is performed by using the modified baseline and orbit. This procedure is implemented iteratively to achieve a higher accuracy DEM. Based on the results of GF-3 interferometric SAR data for Hebei, the effectiveness of the proposed algorithm is verified and the accuracy of GF-3 real-time DEM products can be improved extensively.

Astrocytes are considered to possess a noticeable role in brain metabolism and as a partners in neuron-glia cooperation contribute to synthesis, bioconversions and regulation of the flux of substrates for neuronal metabolism. With the aim to investigate to which extend are human astrocytes metabolizing amino acids and by which compounds are they enriching their surrounding we employed the metabolomics analysis of their culture media by 1H-NMR. In addition, we compered the composition of media with either 5 mM or 25 mM glucose. The quantitative analysis of culture media by 1H-NMR revealed that astrocytes readely dispose from their milieu glutamine, branched-chain amino acids, and pyruvate with significantly high rate, while they enrich the culture media with lactate, branched-chain keto acids, citrate, acetate, ketone bodies, and alanine. The hyperglycemia suppressed the capacity of astrocytes to release branched-chain amino acids while stimulating the generation of ketone bodies. Our results highlight the active involvement of astrocytes in metabolism of several amino acids, and the regulation of key metabolic intermediates. The observed metabolic activities of astrocytes provide valuable insights into their roles in supporting neuronal function, brain metabolism, and intercellular metabolic interactions within the brain. Understanding the complex metabolic interactions between astrocytes and neurons is essential for elucidating brain homeostasis and the pathophysiology of neurological disorders.

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs under challenging metabolic environments. However, since normal diets provide all AAs at relatively constant levels and ratios, these potentially lethal genetic and metabolic defects are eventually harmless to cancer cells. If we temporarily replace the normal diet of cancer patients with artificial diets in which the levels of specific AAs are manipulated, cancer cells may be unable to proliferate and survive. This article reviews in vivo studies that have evaluated the antitumor activity of diets restricted or supplemented with the 20 proteinogenic AAs, individually and in combinations. It also reviews our recent studies that show that manipulating the levels of several AAs simultaneously can lead to marked survival improvements in mice with metastatic cancers.

Leukemia is a form of blood cancer that results in an increase in the number of white blood cells in the body. The correct identification of Leukemia at any stage is essential. The current traditional approaches rely mainly on field expertise' knowledge, which is time consuming. The poor understanding and a long period of examination might damage the human body. In this situation an automated Leukemia identification delivers more reliable and accurate diagnostic information. To effectively diagnose acute lymphoblastic Leukemia from blood smears pictures, a new strategy based on traditional image analysis techniques with machine learning techniques, and a composite learning approach was constructed in this experiment. To identify the type of acute Leukemia first, four well-known machine learning models were utilized. It was discovered that Support Vector Machine (SVM) Provides the highest accuracy in this scenario. To boost the performance, a deep learning model Resnet50 was hybridized with SVM model. Finally, it was revealed that this composite approach achieved 99.9% accuracy.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

NS-3 is one of the most used Network Simulators because it includes different modules, applications and protocols to simulate a wide range of network. Since new proposals usually involve a large number of simulations, a procedure to automatize the simulation process and extract statistics is very useful. "Statistical Framework" (SF) is an important module of NS-3 because it fulfills this need. SF allows us to collect simulation data and obtain statistical reports for NS-3. In this report, we present a detailed description of statistical framework module and two useful examples of its configuration.

Network Simulators is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. Many problems can be solved by using network simulators such as NS-3. With this in mind, the aim of this article is to introduce new NS-3 users through detailed information. It is sometimes difficult to handle by new users the traditional manuals developed by NS-3 project official website. In this article, NS-3 for communication network and Eclipse Integrated Development Environment (IDE) for powerful programming language are integrated step-by-step, explaining the main features of these open source software packages and concluding with an example simulation. Our effort is to make it easy for a beginner to be part of the NS-3 research community and to maintain an open environment of knowledge.

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

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

Global wastes accumulate at an accelerating rate especially food and slaughterhouse waste constituting a major proportion owing to inefficient management. The high protein concentration of fish waste and keratinaceous byproducts is hazardous, harbouring pathogens, and emitting toxins. Transforming proteinaceous waste into amino acids (AAs) reduces waste bulk and offers a smarter nutrient approach for agriculture. However, this resource remains underutilized triggering eco-system pollution, diseases spreading, and climate change. Currently, small quantities of proteinaceous waste are valorized as animal feed, fertilizer, and in medical, and biotechnological sectors, which cannot solve bulk waste accumulation further, natural AA sources in agriculture are less recognized meanwhile researchers focus on synthetic AAs. Introducing various plant-nutrient formulas enriching fish AA with keratinaceous waste hydrolysate has not been broadly discussed. With this novel approach, using proteinaceous waste resources in agriculture would solve environmental pollution while minimizing land degradation by synthetic fertilizer. In this review, we illustrate the potential and benefits of valorizing proteinaceous waste in bulk through bioconversion. More importantly, we spotlight the biocompatibility of natural AAs and propose an enrichment, to use the ultimate product as catalysts for crops. Consequently, this approach reduces hazardous waste while paving a paradigm change in agriculture.

Conventional MRI sequences are standard methods to monitor patients with brain tumors but have significant limitations especially after irradiation. Currently, the role of FET-PET in radiotherapy of glioblastoma is emerging, starting from target definition, response assessment and in distinguishing progression from post-irradiation changes. Recently a PET RANO criteria have been published providing optimal strategy for treatment evaluation with amino-acid PET. Earlier, a PET/RANO group reported contribution of PET imaging to radiotherapy planning and monitoring in glioma patients. Also, increasing evidence have showed advantages of amino-acid PET vs. RANO MRI for prediction of overall survival. In this narrative review we aimed to summarize published data on FET-PET based treatment response assessment to radiotherapy and focused on details in protocols.

The house cricket (Acheta domesticus L.) is one of four edible insect species introduced to the EU market as a novel food and alternative protein source. Innovative products, such as cricket flour, are increasingly appearing on supermarket shelves and can offer an alternative to traditional cereals, while providing the body with many valuable nutrients of comparable quality to those found in meat and fish. The aim of this study was to investigate the possibility of using cricket powder as a substitute for wheat flour in the production of bread. The physicochemical properties of cricket powder were evaluated in comparison to wheat flour, such as water and fat binding capacity, pH, water activity, colour, water content, protein, fat, fibre content and amino acid and fatty acid profile. As a result of the echnological studies, the composition of breads with 5%, 10% and 15% replacement of wheat flour by cricket flour was designed and their quality characteristics (physicochemical, sensory and microbiological) were evaluated. Cricket powder was character-ised by higher protein (63% vs. 13.5%) and fat (16.3% vs. 1.16%) content and a lower carbohydrate (9.8% vs. 66%) and fibre (7.8% vs. 9.5%) content as compared to wheat flour. The tested preparations had similar pH (6.9 and 6.8, respectively for cricket powder and flour), and fat-binding properties ( 0.14 vs. 0.27 g oil/g powder respectively for cricket powder and flour) but different water-binding properties and completely different color components. Despite the differences obtained in phys-icochemical properties for cricket powder and flour, most of the functional parameters obtained for bread with 5% cricket flour were not significantly different from the control sample. All breads had good microbiological quality after baking and during 7 days storage. The 10 and 15 per cent cricket flour treatments affected the darker colour of the breads and caused a significant increase in the hardness of the breads. In the overall sensory evaluation, the bread with 5% cricket flour did not differ significantly from the control bread, while the breads with higher levels of cricket flour had significantly lower overall scores compared to the control sample. In all cases, cricket flour in-creased the protein and fat content and decreased the carbohydrate content compared to the control sample. Considering nutritional properties such as high protein digestibility, breeding consid-erations, relatively low environmental impact and the possibility of intensive production in places where traditional agricultural production is not possible, insects seem to be the future of human nutrition.

In this study, we once again use a set of Fibonacci-like sequences to examine the symmetries within the genetic code. This time, our focus is on the physiological state of the amino acids, considering them as charged, in contrast to our previous work where they were seen as neutral. In a pH environment around 7.4, there are four charged amino acids. We utilize the properties of our sequences to accurately describe the symmetries in the genetic code table. These include Rumer’s symmetry, the third-base symmetry and the "ideal" symmetry, along with the "supersymmetry" classification schemes. We also explore the special chemical structure of the amino acid proline, presenting two perspectives—shCherbak’s view and the Downes-Richardson view, which perspectives are included in the description of the above-mentioned symmetries. Our investigation employs also elementary modular arithmetic to precisely describe the chemical structure of proline, connecting the two views seamlessly. Finally, our Fibonacci-like sequences prove instrumental in quickly establishing the multiplet structure of non-standard versions of the genetic code. We illustrate this with an example, showcasing the efficiency of our method in unraveling the complex relationships within the genetic code.

Growing food autonomously on Mars is challenging due to the Martian soil's low nutrient content and high salinity. Understanding how plants adapt and evaluating their nutritional attributes are pivotal for sustained Mars missions. This research delved into the regeneration, stress tolerance, and dietary metrics of sweet potato (Ipomoea batatas) across different Mars Global Simulant (MGS-1) concentrations (0, 25, 50, and 75%). In our greenhouse experiment, 75% MGS-1 concentration most significantly inhibited sweet potato growth, storage root biomass, and chlorophyll content. This concentration also elevated plant tissues' H2O2, proline, and ascorbic acid levels. Higher MGS-1 exposures (50 and 75%) notably boosted vital amino acids and sugar groups in the plant's storage roots. Yet, increased MGS-1 concentrations notably diminished the total C: N ratio and elemental composition in both vines and storage roots. In summary, sweet potato exhibited optimal growth, antioxidant properties, yield, and nutrient profiles at 25% MGS-1 exposure, compared to higher concentrations. This study underscores the need for future interventions, like nutrient enhancement and controlled metal accessibility, to render it a suitable plant for space-based studies.

Three edible aquatic weeds, helencha (Enhydra fluctuans), malancha (Alternanthera philoxeroides), and kalmi (Ipomoea aquatica), were used to produce edible paper sheets. The composition of the raw and paper sheet samples was analyzed, including proximate composition, amino acid content, minerals and heavy metal contents, and bioactive compounds. The dried raw and paper sheets showed similar proximate composition, with carbohydrates being the highest (50.38-64.63%), followed by crude protein (15.25-19.13%), ash (9.30-15.88%), and lipid (1.549-3.43%). The weeds and paper sheets were rich in essential minerals like Na, Ca, Zn, and Fe. Acceptable levels of heavy metals, including Ni, Pb, and Cu, were found. The paper sheets contained seven essential and eight non-essential amino acids. A. philoxeroides sheets showed the highest amino acid content (16146.81mg/100g), while I. aquatica showed the lowest (13118.67 mg/100g). The aquatic weeds paper sheets were rich in containing bioactive compounds and the number in E. fluctuans, A. philoxeroides, and I. aquatica paper sheets were 31, 33, and 40, respectively. There were no significant changes in the nutritional content of aquatic weeds in paper sheet form compared to the raw weeds which suggests promising prospects for the production and consumption as a source of nutrition and bioactive compounds.

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration.

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration.

A non-steady state mathematical model of amino acid (phenylalanine (Phe)) and mineral salt (NaCl) solution separation by neutralization dialysis (ND) carried out in a batch mode is proposed. The model takes into account the characteristics of membranes (thickness, ion-exchange capacity and conductivity) and solutions (concentration, composition), as well as the flow rate of the solution in the dialyzer compartments. As compared to previously developed models, the new one considers the local equilibrium of Phe protolysis reactions in solutions and membranes and, also, the transport of all the phenylalanine forms (zwitterionic, positively and negatively charged) through membranes. A series of experiments on ND demineralization of NaCl and Phe mixed solution was carried out. In order to minimize Phe losses, the solution pH in the desalination compartment was controlled by changing the concentrations of the solutions in the acid and alkali compartments of the ND cell. The validity of the model was verified by comparison of simulated and experimental time dependencies of solution electric conductivity and pH, as well as the concentration of Na+, Cl– ions and Phe species in the desalination compartment. Based on the simulation results, the role of Phe transport mechanisms in the losses of this amino acid during ND was discussed.

The liver performs a fundamental role in the regulation of diverse physiological processes. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, offer complete protection to the organ, or aid in regenerating hepatic cells. Thus, it is necessary to identify alternative plant-origin pharmaceuticals more effective and less toxic for the treatment of hepatic diseases. The aim of this research was to establish the chemical composition of the American cranberry (Oxycoccus macrocarpus) leaves extract and its aminoacids preparations as well as their hepatoprotective activity. 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 2 catechins, and 3 hydroxycinnamic acids) and main amino acids (valine, arginine, glycine, histidine, aspartic acid, and taurine) were identified and quantified in the American cranberry (O. macrocarpus) leaves extract and its 7 aminoacids preparations. The therapeutic and prophylactic consumption of the American cranberry leaves extracts led to a decrease in the intensity of the lipid peroxidation process compared to the control pathology group in the experiment of acute toxic damage to the liver by tetrachloromethane on rats. The most pronounced hepatoprotective activity was established for the American cranberry leaves extracts’ preparations with arginine and valine.

A prominent feature of stress-tolerant microalgae is their versatile metabolism allowing then to synthesize a broad spectrum of molecules with beneficial effects on many aspects of human body functioning. This is in line with the current understanding that many stress-induced deleterious processes in the human body and in photosynthetic cell are mediated by the same mechanisms such as free-radical attacks and lipid peroxidation. These related risks are kept at bay by optical screening of harmful UV, enzymatic ROS elimination systems, and potent low-molecular antioxidants. Microalgae synthesize a broad spectrum of compounds exerting antioxidant and/or UV-absorbing properties. In microalgae, they increase stress-resilience of these organisms. In human body, they exhibit photoprotective, antiaging, and sunscreen activities. Therefore, these algal metabolites were recognized as promising ingredients for innovative cosmetics and cosmeceutical formulations. Ever increasing effort is being invested into the search for new natural biologically active substances from microalgae. This trend is also fueled by the growing demand for natural raw materials for food, pharmaceuticals and cosmetology associated with the global transition to a "greener" lifestyle. Here, we review the currently accumulated knowledge about the main groups of cosmeceutical compounds from microalgae.

Summary CoV-GLUE is an online web application for the interpretation and analysis of SARS-CoV-2 virus genome sequences, with a focus on amino acid sequence variation. It is based on the GLUE data-centric bioinformatics environment and provides a browsable database of amino acid replacements and coding region indels that have been observed in sequences from the pandemic. Users may also analyse their own SARS-CoV-2 sequences by submitting them to the web application to receive an interactive report containing visualisations of phylogenetic classification and highlighting genomic variation of potentially high impact, for example linked to primer mismatches.Availability and implementation Available at http://cov-glue.cvr.gla.ac.uk. Implemented using GLUE, an open source framework for the development of virus sequence data resources. Contact josh.singer@glasgow.ac.uk

Single molecule de novo protein sequencing based on the 'superspecificity' of amino-acyl tRNA synthetases (aaRS) is proposed. An unfolded protein molecule is threaded through a nanopore in an electrolytic cell (e-cell) to expose the terminal residue in the e-cell's trans chamber. After the residue is cleaved with an exopeptidase, a set of tRNAs, their aaRSs, and ATP are added to trans. An aaRS charges a cognate tRNA molecule with the residue. The charged tRNA (along with the other reactants) is transferred to an extended e-cell with N (20 ≤ N ≤ 61) pores in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is exposed in trans. The charged tRNA's anticodon base-pairs with the terminal codon of an RNA. If tRNAs and residues are fluorescently tagged with two different colors, the residue can be identified from the observed position of the resulting color pair. As charging is 'superspecific' identification is unambiguous. The protein molecule in the first e-cell is advanced by one residue and the process repeated. In this approach there is no need for precise pore current or optical intensity measurements. Potential implementation issues are discussed. Other possibilities, including one in which the terminal residue is cleaved after charging, are also examined.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

This paper describes the preparation and description of four new complexes [Bu₂Sn(AA)Cl] (AA = glycine, DL-valine and L-leucine) and [Bu₂SnPhen₂] (Phen = DL-phenylalanine) They were characterized by elemental analyses of carbon, hydrogen, nitrogen, chlorine and tin; and by infrared, ^119mSn-Mössbauer and ^119mSn-RMN spectroscopies, and by the applications of TG and DSC techniques in dynamic helium atmosphere. For the [Bu₂Sn(AA)Cl], trigonal bipyramidal tin species, AA were coordinated bidentatedly by the carboxylic oxygen and by the NH₂ group. The [Bu₂SnPhen₂)], with tin atoms in trans-octahedral sites, had the Phen-coordinated by both carboxylic oxygen atoms.

In this paper, a new way to obtain photoactive cements was presented. In this method amorphous TiO2 is added to cooler during the cooling of the cement clinker (Górażdże company) during cement production. Amorphous TiO2 was taken from the installation for obtaining titanium dioxide using the sulphate method. During the studies amorphous TiO2 was added to clinker at different temperature 300, 600, 700 and 800 °C. The properties of the obtained cement were tested during the bending and compressive strength and beginning and the end of bending setting time measurements. The adhesion of the obtained materials to concrete block, ceramic brick and plasterboard were also evaluated. The photocatalytic activity of the obtained materials was studied during NO and BTEX (benzene, toluene, ethylbenzene, p-,m-,o-xylenes decomposition) decomposition. Cement with 5 wt.% TiO2 added to clinker at 700 C had the highest photocatalytic activity and the best mechanical properties.

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported even in specialized centers. Mobile health technologies have been used in research settings to overcome these limits with contrasting results. This study aims to evaluate the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Patients were randomly assigned to standard care or standard care plus mobile app (2:1). The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: Seventy-five subjects were prospectively enrolled. At six months of follow-up, the m-app group showed significantly lower dropout rates compared to standard care(p=0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86,95%C.I. 1.39-10.42,p=0.01). After one year of follow-up, we observed lower albeit non statistically significant dropout rates in the m-app compared to the standard care group(p=0.24). No differences were observed in terms of z-score BMI and percentage of BMI reduction between the two groups. Conclusion: our findings suggest that mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in many neurological disabilities, optic neuritis (ON) is developed in some MS patients. However, the molecular mechanism of ON remains unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiology. We have previously shown that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its animal model for human MS. In the current study, the expression of gal-3 was explored in the visual pathway of the EAE mice to clarify the pathogenesis of ON. Immunohistochemical analysis demonstrated that expression of gal-3 was increased in the visual pathway of the EAE mice during the peak disease, compared with naïve and EAE mice during the chronic disease. Expression of gal-3 was observed in mainly microglia/macrophages and astrocytes in the visual pathway of the EAE mice. In addition, gal-3+Iba-1+ cells with the phagocytic activities reflected by immunostaining with cathepsin-D were accumulated at demyelinating lesions in the visual pathway during peak disease of EAE. Moreover, NLRP3 expression was also detected in most gal-3+Iba-1+ cells. These results indicate a considerable possibility that gal-3 regulates the NLRP3 signaling in microglia/macrophages, followed by neuroinflammatory demyelination in ON. By contrast, astrocytic expression of gal-3 was also observed from the peak to the chronic disease. Taken together, the current study suggests a critical role of gal-3 in the pathogenesis of ON and proposes gal-3 in glial cells as a potential therapeutic target for ON.

The patient was a 44-year-old woman with suspected Stevens-Johnson syndrome due to Baktar® (sulfamethoxazole trimethoprim) medication received at our outpatient dermatology clinic. Histopathological examination of the epidermis, dermis, and subcutaneous adipose tissue samples showed numerous necrotic keratinocytes in the epidermis. Apoptotic nuclei were visualized as diaminobenzidine brown deposits with immunoperoxidase staining for cleaved caspase-3. Cleaved-caspase3-positive findings were consistent with eosinophilic material that appeared to be necrotic cells within the epidermis. Therefore, these eosinophilic materials must be apoptotic bodies. Generally speaking, and especially in Japan, these materials are considered necrotic keratinocytes. To our best knowledge, no studies have used apoptotic immunohistochemical markers to examine whether these structures are apoptotic.

Crohn's disease is a non-specific inflammatory bowel disease, which is a chronic condition that affects the ileum and/or large intestine. At the same time, it can also involve any other part of the human body, that is, from the mouth to the anus. The symptoms are very bothersome and cause a significant reduction in quality of life and sometimes even crippling permanent damage to the gastrointestinal tract, which requires enteral or parenteral nutrition for life. The purpose of this study was to investigate tissue metalloproteinases as markers of recurrent Crohn's disease. The experimental groups included 31 patients and 10 patients with normal Crohn's disease, ranging in age from 23-70 years, with a mean age of 40.4. Collected tissues were frozen and then fragmented tissues were homogenized with Ripa Lysis buffer on ice. The supernatant was collared and four metalloproteinases - MMP 3, MMP 7, MMP 8 and MMP 9 - were an-alized by Enzyme-linked Immunosorbent Assay using SEA101HU, SEA102Hu, SEA103Hu and SEA553Hu kits (Cloud-Clone Corp., Kata, TX, USA). All chemical analyses were performed in triplicate. Metalloproteinase content was expressed as mean ± standard deviation. Metalloproteinase 3 and metalloproteinase 8) significantly influenced the possibility of Crohn recurrence

The antibodies targeting invasive proteins of Plasmodium falciparum (Pf) merozoites is a clever strategy against malaria parasite. The recent finding that Plasmodium merozoites surface enolase is a target for growth neutralizing antibodies has generated interest in identifying its re-ceptor (s) on erythrocytes. In the present study, several biochemical experiments were undertaken involving recombinant Pf enolase and antibody against it to search for its cognate receptor. The binding of rPfeno to erythrocytes was selectively sensitive to trypsin but resistant to neuramini-dase. Failure of yeast enolase binding to human red blood cells under similar conditions indicat-ed high specificity of parasite Pfeno. The mass spectrometric and immunological analyses of pro-teins obtained in pull downs and co-immunoprecipitation samples led to identification of band 3 as an interactor/receptor for Plasmodium enolase. Structural characterization of sequences of band 3 - rPfeno interacting regions revealed C-terminal exocytic regions of band 3 to be binding to Pfeno. Similarly, band 3 binding regions of rPfeno were also identified. Identification of receptor-ligand (band 3: Pfeno) pair paves the way for antimalarial anti-Pf enolase-based vaccine, anti-Pf enolase antibodies as drug and also for developing novel small molecule-based invasion inhibi-tory therapeutics including peptidomimetics that could disrupt the band 3: Pfeno protein-protein interactions.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

Let $\mathcal{N}$ be an arbitrary class of matroids, closed under isomorphism. For $k$ a positive integer, we say that $M \in \mathcal{N}$ is \emph{$k$-minor-irreducible} if $M$ has no minor $N \in \mathcal{N}$ such that $1\leq\left|E\left(M\right)\right|-\left|E\left(N\right)\right|\leq k $. Tutte's Wheels and Whirls Theorem establish that, up to isomorphism, there are only two families of 1-minor-irreducible matroids in the class of 3-connected matroids. More recently, Lemos classified the 3-minor-irreducibles with at least 14 elements in the class of triangle-free 3-connected matroids. Here we prove a local characterization for the 2-minor-irreducible matroids with at least 11 elements in the class of triangle-free 3-connected matroids. This local characterization is used to establish two new families of 2-minor-irreducible matroids in this class.

Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no proinflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.

This document describes the theoretical basis of the algorithms used to determine properties of snow and ice from the measurements of the Ocean and Land Color Instrument (OLCI) onboard Sentinel-3 satellites within the Pre-operational Sentinel-3 snow and ice products (SICE) project: http://snow.geus.dk/. The code used for the SICE retrieval and its documentation can be found at https://github.com/GEUS-SICE/pySICE. The algorithms were developed after the work from Kokhanovsky et al. (2018, 2019, 2020).

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.

Network Simulators (NS) is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. This is the case of Mobile Ad hoc Networks (MANETs) which can be extensively used in emergency situations or to gather information without infraestructure. An important factor to get realiable results in the MANETs’ simulations is the wireless channel module of NSs. In this report, we explain how thw wireless channel is implemented in NS-3 and it can be configured.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

The metabolomics of Newhall navel oranges with geographical indication (GI) was measured by LC-MS/MS from three areas Ganzhou, Fengjie, and Zigui in China. Orthogonal partial least squares-discriminant analysis was performed for samples classification and important metabolites identification. This approach identified the best markers (i.e. tricarboxylic acid, amino acids, and phenolics) of the geographical origin able to discriminated Fengjie, Ganzhou, and Zigui organge samples. The results showed that peeled-samples from Zigui were richest and those from Fengjie lowest in all of the top ten most important markers. In whole samples, the highest levels of seven important markers occurred in those from Zigui, and the other three important markers appeared the highest levels in those from Ganzhou. According to the variation of the best markers, and the highest value of titratable acidity in those from Zigui, the samples planted in Ganzhou have the best balance between taste and nutrition. This work confirms the approach of metabolomics combined with OPLS-DA is an effective way for origin tracing and overall quality evaluation.

Background: Current treatment for Chronic Kidney Disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KA), calcum citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process; Methods: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts; Results: Supplementation of low protein diets (LPD) and very low protein diets (VLPD) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities; Conclusions: Based on a combination of clinical experience and scientific evidence , the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.

Sulfur and selenium-containing organic compounds (amino acids and xenobiotics) have received interests as potential medicines, sources of the selenium and antioxidants. The purpose of the study was to comparatively investigate the antioxidant capacity of sulfur- and selenium-containing amino acids, xenobiotics and the study of possible mimetic properties of selenocystine. To evaluate the antioxidant capacity, coulometric oxidation with electrogenerated bromine was used. Methionine, cystine and selenocystine react with bromine quickly and quantitatively. Diacetophenonyl selenide, ebselen and selenopyran are oxidized nonstoichiometrically, but show high antioxidant capacity. We hypothesized that selenium xenobiotcs might be exert prolonged antioxidant effect. Conditions have been optimized to determine antioxidant capacity of selenium and sulfur substances in water and methanol. We proposed theory and reactions schemes for the interaction of bromine with methionine, cystine, selenocystine diacetophenonylselenide, ebselen, thiopyran and selenopyran. Antioxidant capacities in both water and methanol decrease in the following order: L-cystine &gt; L-selenocystine &gt; methionine. Sulfur-containing substances in methanol show higher antioxidant capacity than selenium-containing antioxidants. Among selenium-containing xenobiotics, DAPS shows the highest antioxidant capacity (comparable to cystine). Selenopyran and ebselen are less active as antioxidants. Diselenide bond is a selenocystin chromophore for its UV-assay. For the first time we demonstrated the ability of selenocystine to be actively involved in redox reactions and to act as a mimetic, a low-molecular-weight analogue of glutathione peroxidase.

GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species. Although it is known that GCN1 and GCN2 interact with ribosomes to accomplish amino acid starvation sensing, recent studies have reported that GCN1 binds to disomes (i.e. ribosomes that collide each other), thereby regulating both the co-translational quality control and stress response. We propose that GCN1 regulates ribosome-mediated signaling by dynamically changing its partners among RWD domain-possessing proteins via unknown mechanisms. We recently demonstrated that GCN1 is essential for cell proliferation and whole-body energy regulation in mice. However, the manner in which ribosome-initiated signaling via GCN1 is related to various physiological functions warrants clarification. GCN1-mediated mechanisms and its interaction with other quality control and stress response signals should be important for proteostasis during aging and neurodegenerative diseases, and may be targeted for drug development.

The incidence of celiac disease and gluten intolerance has been significantly rising globally. Gluten-free product consumption registered a sudden rise also among tolerant people, due to psychosocial factors. Biscuits are popular, low-cost bakery foods, consumed by nearly everyone worldwide. The removal of gluten from the baked product causes some undesirable traits and different textures and tastes. The main goal consists of creating a food product with the same taste and texture as a product with gluten. Moreover, gluten-free bakery products are usually low-grade sources of protein and poor in dietary fiber. Quinoa is a source of TDF and valuable protein. In this study, quinoa flour was used as the main constituent in the formulation of gluten-free c to improve their nutritional properties. Six different recipes with different percentages of quinoa flour have been realized. The formulations were compared, by rheological analysis, of each other and with a wheat flour control shortbread. The recipes with rheological features more similar to control shortbread were subjected to a discrimination analysis and the preferred was characterized from a chemical-physical and sensorial point of view. The experimental shortbreads constituted a good compromise to exploit the good nutritional composition of quinoa maintaining an acceptable sensory profile.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to treat with hypothermic therapy is critical. Differentiating HIE from other neonatal conditions, such as sepsis, further complicates the diagnosis. This study investigated the utility of a metabolomic-based approach using the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic accuracy of this method between 3 and 6 hours after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic accuracy with areas under the curve (AUC) of 0.94 at 3 hours and 0.96 at 6 hours after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 hours of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

The emergence of non-canonical amino acids (ncAAs) has enriched the functional pool inherent in canonical amino acids (cAAs). ncAAs are important building blocks in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis because of its environmental friendliness and high efficiency. The breakthrough genetic code expansion (GCE) technique developed in recent years has allowed for the incorporation of ncAAs into target proteins, giving them special functions and biological activities. Biosynthesis of ncAAs and their incorporation into target proteins within a single microbe has become an enticing application of such molecules. Based on that, in this study we first review the biosynthesis methods for ncAAs and analyze the difficulties in biosynthesis. We then summarize the GCE methods and analyze their advantages and disadvantages. Further, we review the application progress of ncAAs and anticipate the challenges and future development directions of ncAAs.

Canine mammary tumors (CMTs) are among the most common disease in female dogs and share similarities with human breast cancer, which have placed these animals as a model of study in comparative oncology. Metabolic reprogramming is one of them and is known as a hallmark of carcinogenesis whereby cells undergo adjustments to supply the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as therapeutic strategies which have been tested mostly in human clinical trials, but poorly explored in CMTs. In this dedicated review, we compilated the metabolic changes described for CMTs emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial function. We observed here key factors associated with the presence and aggressiveness of CMTs, such as the increase in glucose uptake followed by enhanced anaerobic glycolysis via upregulation of glycolytic enzymes, changes in glutamine catabolism due to overexpression of glutaminases, raise in fatty acid oxidation and distinct effects depending on the lipid saturation, in addition to mitochondrial DNA which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.