Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix, and in mice fed with EAA rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing autophagy and apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable anti-proliferative properties.

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.

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

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.

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.

Tree peony flowers are traditional ornamental and medicinal materials in China. In this study, 23 tree peony flowers at a broad color spectrum were analyzed. Gas chromatography-mass spectrometer (GC-MS) revealed that tree peony flowers are rich in sugars and organic acids. Up to 18 amino acids were identified by liquid chromatography-mass spectrometer (LC-MS), including all essential amino acids, except for methionine. The majority of amino acids were significant positively correlated with each other and were significant negatively correlated with glucose, fructose and galactose. A total of 11 polyphenols were identified in these tree fresh peony flowers by LC-MS. There was a high consistency in grouping peony flowers by using sugars and organic acids and amino acids, which differed from that based on color components and polyphenols. Tree peony flowers are also rich in K, Ca, Mg and Fe. In together, peony flowers can be a good resource of health-promoting compounds.

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.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

We research the interaction between six representative carbon-based nanoparticles (CBNs) and 20 standard amino acids through all-atom molecular dynamics simulations. The six carbon-based nanoparticles are fullerene(C60), CNT55L3, CNT1010L3, CNT1515L3, CNT2020L3, and two-dimensional-graphene(Graphene33). Their curvatures decrease sequentially, and all of CNT are single-walled carbon nanotubes. We have observed that as the curvature of CBNs decreases, the adsorption effect of 20 amino acids with them has an increasing trend. In addition, we also used multi-dimensional clustering to analyze the adsorption effects of 20 amino acids on six carbon-based nanoparticles. We observed that the π-π interaction still plays an extremely important role in the adsorption of amino acids on carbon-based nanoparticles. Individual long-chain amino acids and “Benzene-like” Pro also have a strong adsorption effect with carbon-based nanoparticles.

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.

Abstract: Amino acids are widely present as intermediates in marine nitrogen cycle. However, the information of amino acid distribution in deep-sea seawater, especially in abyss and hadal zone, is very limited. In the present study, we determined the concentrations of dissolved free amino acids (DFAA), dissolved combined amino acids (DCAA) and total hydrolysable amino acids (THAA) in the seawater from sea surface to hadal zone of the Yap Trench. Their occurrence, vertical variations and degradation behavior in the Yap Trench were investigated. The results showed that concentrations of ΣDFAA, ΣDCAA and ΣTHAA ranged from 0.09 to 1.78, 0.99 to 17.69 and 1.18 to 18.01 μmol/L, respectively, in the study area. In the seawater samples from the trench, Glycine (Gly) was the predominant DFAA, while the DCAA and THAA was dominated by threonine (Thr). Concentration of chlorophyll a (chl a) was not significantly correlated with any amino acids (DFAA, DCAA and THAA) in the euphotic layer. Mean concentrations for DFAA, DCAA and THAA in different water layers were in the order of: mesopelagic > euphotic > abyssal > bathyal. The concentrations of DCAA and THAA in sediment-seawater interface were higher than those from the euphotic to abyssal layer. Stations near the Yap Islands have the older organic matter (OM), while the organic matter in stations near the Yap Trench axis was relatively fresh above 1000-m depth. Degradation behavior of OM in the mesopelagic and abyssal layer are affected by transport of dissolved organic matter with water current. The organic matter in the sediment-seawater interface are older, especially on the west side of the trench. This is a survey of amino acids (DFAA, DCAA and THAA) in the Yap Trench, which provides information on the vertical variations and degradation behavior of amino acids from sea surface to hadal environment, and will be helpful to understand marine organic nitrogen cycle.

We studied surface enhanced Raman spectra of amino acids D-alanine and DL-serine and their mixture on silver nanoisland films (SNF), immersed in phosphate buffer saline solution at millimolar amino acid concentrations. It is shown that the spectra from the amino acid solutions differ from the reference spectra for microcrystallites due to electrostatic orientation of amino acid zwitterions by the metal nanoisland film. Moreover, non-additive peaks are observed in the spectrum of the mixture of amino acids adsorbed on SNF, which means that intermolecular interactions between adsorbed amino acids are very significant. The results indicate the need for a thorough analysis of the Raman spectra from amino acid solutions in the presence of a nanostructured metal surface, and may also be of interest for studying molecular properties and intermolecular interactions.

Our work uses Iterative Boltzmann Inversion (IBI) to study the coarse-grained interaction between 20 amino acids and the representative carbon nanotube CNT55L3. IBI is a multi-scale simulation method that has attracted the attention of many researchers in recent years. It can effectively modify the coarse-grained model derived from the Potential of Mean Force (PMF). IBI is based on the distribution result obtained by All-Atom molecular dynamics simulation, that is, the target distribution function, the PMF potential energy is extracted, and then the initial potential energy extracted by the PMF is used to perform simulation iterations using IBI. Our research results have gone through more than 100 iterations, and finally, the distribution obtained by coarse-grained molecular simulation (CGMD) can effectively overlap with the results of all-atom molecular dynamics simulation (AAMD). In addition, our work lays the foundation for the study of force fields for the simulation of the coarse-graining of super-large proteins and other important nanoparticles.

The early diagnosis of mastitis represents an essential factor for a prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. Total amino acid content increases significantly in mastitic milk compared to normal one. Bovine mastitis can arise as a result of infection of the mammary gland by Staphylococcus aureus. Multiplication of this bacterium within the mammary gland is required for infection to persist. S. aureus requires branched-chain amino acids (BCAAs: isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acids synthesis and environmental adaptation by responding to their availability via transcriptional regulators. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. In the present work, we demonstrated, by a direct ion-pairing reversed-phase method based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine and S. aureus load.

qNMR is a valuable technique for metrological studies due to the uniformity of its signal response for all chemical species of an isotope of interest, which enables compound-independent calibration. However, protein quantification remained challenging as large molecules produce wide, low-intensity signals that reduce the already low sensitivity. Combining qNMR with the hydrolysis of protein samples into amino acids circumvents many of these issues and facilitates the use of NMR spectroscopy for absolute protein and peptide quantification.In this work, different conditions have been tested for quantifying aromatic amino acids and proteins. First, we examined the pH-based signal shifts in the aromatic region. The preferable pH depends on the selection of the amino acids for quantification and which internal standard substance should be used to avoid peak overlap. Several aromatic compounds, such as terephthalic acid, sulfoisophthalic acid, and benzene tricarboxylic acid, have been applied as internal standards. The quantification of amino acids from an amino acid standard, as well as from a certified reference material (bovine serum albumin), was performed. Using the first two suggested internal standards, recovery was ~ 97 % for histidine, phenylalanine, and tyrosine at a concentration of approximately 1 mM in solution. Acidic hydrolysis of a certified reference material (CRM) of bovine serum albumin (BSA) and subsequent quantification of Phe and Tyr yielded recoveries of 98 ± 2 and 88 ± 4 %, respectively, at a protein concentration of 16 g/L or 250 µM.

Three different fields intersect in search of an understanding of the point-of-origin of modern-age diseases: 1) D-amino acids and their role under stress conditions; 2) evolutionary origin of the mitochondrion organelle in the eukaryotic cell; and 3) gut microbiota and human healthHere it is first suggested that D-amino acids function as universal signaling agents, after having evolved as prokaryotic communication, part of an organic communication process that governs the basic activities of all the cells and coordinates cell action.Mitochondria (symbiotic prokaryotic organelles), are creative source of D-amino acids as signaling agents in the central nervous system and in the neuroendocrine systems.Amino acids racemases catalyzes the conversion between the L-enantiomers ( protein building blocks) into D-enantiomers (signaling agents).It is suggested that hectic modern life may affect human health by causing stress to the gut microbiota. These affected, gut microbiota then secrete D-amino acids that enter the blood stream, as signaling agents, causing communication errors in the central nervous system, and in the neuroendocrine systems due to excessive quantity of D-amino acids.Treating gut microbiota with inhibitors of amino acids racemases or finding D-amino acid scavengers may be used in developing novel therapeutic strategies for diseases related to the central nervous system and neuroendocrine systems caused by stressed gut microbiota.

The global prevalence of insulin resistance (IR) is increasing continuously, influencing metabolic parameters and fertility as well. The metabolic changes due to IR can alter the molecular composition of plasma and other body fluids. Follicular fluid (FF) is derived mainly from plasma, and it is a critical microenvironment for the developing oocytes. It contains various metabolites and amino acids, and the quality of the oocytes is linked at least partially to amino acid metabolism. Our goal was to determine quantitatively the amino acid (AA) profile of FF in IVF patients and to compare IR and non-insulin resistance (NIR) groups to investigate the AA changes in their FF. By UHPLC-based method we quantified the main 20 amino acids from human FF samples in the IR and NIR groups. Several amino acids (aspartate, glycine, glutamate, and cysteine) differed significantly (p<0.05 or less) between the two groups. The most significant alterations between the IR and NIR groups were related to the glutathione metabolic pathway involving glycine, serine, and threonine. Since insulin resistance alters the amino acid composition of the FF, the oocytes may undergo metabolism-induced changes resulting in poor oocyte quality and less fertility in the insulin resistance groups.

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.

Mitochondrial pyruvate dehydrogenase complex (PDHC) is essential for the brain glucose and neurotransmitter metabolism, dysregulated in many pathologies. Using specific inhibitors of PDHC in vivo, we determine biochemical and physiological responses to PDHC dysfunction. Dose dependence of the responses to membrane-permeable dimethyl acetylphosphonate (Ac-PMe2) is non-monotonous. Primary decreases in glutathione and its redox potential, methionine and ethanolamine are alleviated with increasing PDHC inhibition, the alleviation accompanied by physiological changes. Comparison of 39 brain biochemical parameters after administration of four phosphinate and phosphonate analogs of pyruvate at a fixed dose of 0.1 mmol/kg reveals no primary, but the secondary changes, such as activation of 2-oxoglutarate dehydrogenase complex (OGDHC) and decreased levels of glutamate, isoleucine and leucine. The accompanying decreases in RMSSD of ECG and freezing time are most pronounced after administration of me-thyl acetylphosphinate and dimethyl acetylphosphonate. The levels of PDHA1 expression and phosphorylation, sirtuin 3 and total protein acetylation are not significantly changed by the PDHC inhibitors that affect the brain protein succinylation and glutarylation. Thus, decreased production of the tricarboxylic acid cycle substrate acetyl-CoA by inhibited PDHC is compen-sated by increased degradation of amino acids through the cycle with activated OGDHC, increas-ing total protein succinylation and decreasing anxiety indicators.

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.

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.

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.

Unmetamorphosed carbonaceous chondrites provide important information concerning the formation and evolution of organic matter, such as amino acids. However, terrestrial contamination remains a valid concern when investigating the organic inventory of meteorites that have fallen to Earth. Accordingly, JAXA’s Hayabusa2 and NASA’s OSIRIS-REx have been launched with the task of returning uncontaminated C-type asteroid material to Earth. The successful Hayabusa2 mission has a very limited sample size (5.4 g). Therefore, many conventional compound specific techniques will struggle to detect amino acids above detection limit with available sample amounts (~several mg to 10’s of mg) being much smaller than those typically used. Here a novel method utilizing ultrahigh performance liquid chromatography-Orbitrap-mass spectrometry is validated and applied to very small meteorite samples, thus providing an approach that can overcome the small sample size constraints of sample return missions. The method is highly sensitive, enabling the detection of amino acids in the carbonaceous chondrites Murchison (2.28 mg) and Orgueil (2.30 mg). Furthermore, quantitation was possible for many of the detected amino acids in Murchison and Orgueil. Using the data presented here, both the amino acid reservoirs of Murchison and Orgueil and the potential application of this method to sample return samples are discussed.

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.

Altered amino acid levels have been found in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, it is not clear whether this alteration is due to altered hepatic metabolism or insulin resistance. The aim of this study was to clarify the association among amino acid levels, fatty liver, and liver fibrosis while eliminating the influence of insulin resistance. NAFLD and liver fibrosis were diagnosed using transient elastography and subjects were divided in three groups: normal, NAFLD, and liver fibrosis. To exclude the influence of insulin resistance, the subjects were matched using the homeostasis model assessment of insulin resistance (HOMA-IR). The amino acid serum levels were compared among the groups. Of 731 enrolled subjects, 251 and 33 were diagnosed with NAFLD and liver fibrosis. Although significant differences were observed among the groups in the serum levels of most amino acids, all but those of glutamate and glycine disappeared after matching for HOMA-IR. The multivariate logistic regression revealed that glutamate, glycine, and HOMA-IR were independent risk factors for liver fibrosis. The altered serum levels of most amino acids were associated with insulin resistance, while the increase in glutamate and the decrease in glycine levels were strongly associated not only with insulin resistance, but also with altered liver metabolism in patients with liver fibrosis.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

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.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been linked to changes in amino acid (ΑΑ) levels. The current observational study sought to investigate the relationship between plasma AA concentrations in a NAFLD population and MRI parameters reflecting inflammation and fibrosis, inflammatory and oxidative stress markers, and disease-related anthropometric and biochemical indicators. Approach & Results: Plasma AA levels were quantified with liquid chromatography in 97 NAFLD patients from the MAST4HEALTH study. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers were measured. In total, males and subjects with higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to females and subjects with lower PDFF respectively. Several associations of AAs with disease related markers were revealed, with the more prominent ones being those of aromatic amino acids with log-PDFF (beta: 1.190E-02, p-Value: 0.001) and log-ALT (beta: 7.55E-03, p-Value: 0.001), of branched amino acids with log-insulin (beta: 1.97E-03, p-Value: 1.16E-04) and of ethanolamine (beta: 0.036, p-Value: 3.65E-04) and L-ornithine (beta: 5.4E-04, p-Value: 0.021) with log-total antioxidant status (TAS). Conclusions: Plasma AA levels varied according to sex, BMI, and several MRI clinical factors. Furthermore, significant relationships were demonstrated between AA and several disease indicators, such as MRI parameters, biochemical and oxidative stress indices, showing the potential utility of AAs as diagnostic dis-ease-related indicators activity.

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.

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.

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

Microbial competition within plant tissues affects invading pathogens' fitness. Metabolomics is a great tool for studying their biochemical interactions by identifying accumulated metabolites. Xylella fastidiosa, a Gram-negative bacterium causing Pierce's disease (PD) in grapevines, secretes various virulence factors including cell wall degrading enzymes, adhesion proteins, and quorum sensing molecules. These factors, along with outer membrane vesicles, contribute to its pathogenicity. Previous studies demonstrated that co-inoculating X. fastidiosa with Paraburkholderia phytofirmans strain PsJN suppressed PD symptoms. Here, we further investigated the interaction between the phytopathogen and the endophyte by analyzing the exometabolome of wild-type X. fastidiosa and a diffusible signaling factor (DSF) mutant lacking quorum sensing, cultivated with 20% P. phytofirmans spent media. LC-MS and MAGI were used to detect and map metabolites to genomes revealing a total of 121 metabolites, of which 25 were further investigated. These metabolites potentially relate to host adaptation, virulence, and pathogenicity. Notably, this study presents the first comprehensive profile of X. fastidiosa in the presence of P. phytofirmans spent media. The results highlight that P. phytofirmans and the absence of a functional quorum sensing affect the ratios of glutamine to glutamate (Gln:Glu) in X. fastidiosa. Additionally, two compounds with plant metabolism and growth properties, 2-Aminoisobutyric acid and Gibberellic Acid, were downregulated when X. fastidiosa interacted with P. phytofirmans. These findings suggest that P. phytofirmans-mediated disease suppression involves modulation of the exometabolome of X. fastidiosa, impacting plant immunity.

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this preliminary study, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for controls). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S individuals was defined by higher levels of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older individuals with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

The influence of humic aggregates in water solution upon the chemical stability under basic conditions of different substrates has been reviewed. The kinetic behavior of each substrate has been modelized in terms of micellar pseudophase model.

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.

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.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Nowadays, there is extensive production and use of plastic materials for different industrial activities. These plastics, either from their primary production sources or through degradation processes of the plastics themselves, can contaminate the ecosystem with micro and nanoplastics. Once in the aquatic environment, these microplastics can be the basis for the adsorption of chemical pollutants, favoring that these chemical pollutants disperse more quickly in the environment and can affect living beings. Due to the lack of information on adsorption, three machine learning models (random forest, support vector machine, and artificial neural network) to predict different microplastic/water partition coefficients (log Kd) were developed using two different approximations (based on the number of input variables). The best-selected machine learning models present, in general, correlation coefficients upper than 0.92 in the query phase, which indicate that these type of models could be used for a rapid estimation of the absorption of organic contaminants on microplastics.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.

Background: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. Methods: eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6±0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total aminoacids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. Results: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. Conclusions: This study confirms the finding in aged patients of an alteration in levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/ 18F]exchange reaction over IDIF in dimethylsulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7±3% radiochemical yield in a 20 minutes reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t>10 min post administration), rapid accumulation in the liver, long circulation time and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

A thorough analysis and comparison of the fatty acid profiles of stipe and blade from Laminaria hyperborea, a kelp species found in the northern Atlantic, is presented. Lipids were extracted and fractionated into neutral lipids, free fatty acids and polar lipids, then derivatized to fatty acid methyl esters prior to GC-MS analysis. A total of 42 fatty acids were identified and quantified, including the n-3 fatty acids α-linolenic acid, stearidonic acid and eicosapentaenoic acid. An n-6/n-3 ratio of 0.8:1 was found in blade and 3.5:1 in stipe, respectively. The ratios vary between the lipid fractions within stipe and blade, with the lowest ratio in the polar lipid fraction of blade. The fatty acid amounts are higher in blade than in stipe, and the highest amounts of n-3 fatty acids are found within the neutral lipid fractions. The amounts of polyunsaturated fatty acids are 3.4 times higher in blade than stipe. This study highlights the compositional differences between the lipid fractions of stipe and blade from L. hyperborea. The amount of polyunsaturated fatty acids, compared to saturated- and monounsaturated fatty acids, as well as the n-6/n-3-ratio, is known to influence human health. In the pharmaceutical, food, and feed industries this can be of importance for production and sale of different health products. Additionally, lipids are today among the unused by products of alginate production, exploiting this material for commercial interest should give both economical and environmental benefits.

The members within the genus Thermoanerobacter have been much less investigated for protein and amino acid metabolism as compared with carbohydrates. The present study investigates the biotechnological potential of Thermoanaerobacter mathranii (DSM 11426) concerning its ability to produce high energy alcohols from amino and fatty acids. End-product formation was analyzed from glucose in the presence and absence of butyric acid as well as from selected proteins, and all amino acids. T. mathranii did not degrade any of the proteins tested to a large extent but de-grade several amino acids, namely serine and the branched-chain amino acids (leucine, isoleu-cine, valine) when cultivated in the presence of thiosulfate. The main end products from the branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. 13C2-labeled leucine revealed that the strains degraded the amino acid in the pres-ence of thiosulfate, producing 3-methyl-1-butyrate, which was then used as an electron acceptor which led to the accumulation of 3-methyl-1-butanol. The strain is highly ethanologenic, pro-ducing more than 1.2 mol ethanol per mol of glucose degraded. The strain was able to reduce volatile fatty acids during glucose fermentation to their corresponding alcohol, further suggest-ing this strain may be of greater biotechnological value beyond bioethanol production.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, led to the design of nucleotide analogs that when being part of these oligomers enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs are the first-generation bridge nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second generation BNA, BNANC (2'-O,4'-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but in some cases also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds were researched, the results are very promising warranting more efforts in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future offering great hope to oligonucleotide-based fields of research and applications.

Highly pathogenic (HP) avian influenza viruses (AIVs) are naturally restricted to H5 and H7 subtypes with a polybasic cleavage site (CS) in the hemagglutinin (HA) and any AIV with an intravenous pathogenicity index (IVPI) ≥1.2. Only few non-H5/H7 viruses fulfill the criteria of HPAIVs; nevertheless, it remains unknown why these viruses did not spread in domestic birds. In 2012, a unique H4N2 virus with a polybasic CS 322PEKRRTR/G329 was isolated from quails in California which, however, was avirulent in chickens. This is the only known non-H5/H7 virus with four basic amino acids in the HACS. Here, we investigated the virulence of this virus in chickens after expansion of the polybasic CS by substitution of T327R (322PEKRRRR/G329) or T327K (322PEKRRKR/G329) with or without reassortment with HPAIVs H5N1 and H7N7. The impact of single mutations or reassortment on virus fitness in vitro and in vivo was studied. Efficient cell culture replication of T327R/K carrying H4N2 viruses increased by trypsin, particularly in MDCK cells, and reassortment with HPAIV H5N1. Likewise, replication, virus excretion and bird-to-bird transmission of H4N2 was remarkably compromised by the CS mutations, but restored after reassortment with HPAIV H5N1, although not with HPAIV H7N7. Viruses carrying the H4-HA with or without R327 or K327 mutations and the other gene segments from HPAIV H5N1 exhibited high virulence and efficient transmission in chickens. Together, increasing the number of basic amino acids in the H4N2 HACS was detrimental for viral fitness particularly in vivo but compensated by reassortment with HPAIV H5N1. This may explain the absence of non-H5/H7 HPAIVs in poultry.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines.

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

The development of new and effective antimicrobial compounds is an urgent need with the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 have the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess a large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safest compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.

Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAA) that must be available in the diet, along with those AAs that the cells can synthesize, the dispensable amino acids. Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.

Ursolic and oleanolic acids are secondary plant metabolites that are known to be involved in the plant defence system against water loss and pathogens. Nowadays these triterpenoids are also regarded as potential pharmaceutical compounds and there is mounting experimental data that either purified compounds or triterpenoid-enriched plant extracts exert various beneficial effects, including anti-oxidative, anti-inflammatory and anticancer, on model systems of both human or animal origin. Some of those effects have been linked to the ability of ursolic and oleanolic acids to modulate intracellular antioxidant systems and also inflammation- and cell death-related pathways. Therefore, our aim was to review the current knowledge about the distribution of ursolic and oleanolic acids in plants, bioavailability and pharmacokinetic properties of these triterpenoids and their derivatives, and to discuss their neuromodulatory effects in vitro and in vivo.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

As novel materials for carbon capture, phase change solvents can separate into two immiscible phases during the CO2 capturing procedure under a certain temperature. The solvent systems can significantly decrease the energy consumption since the solvents can be regenerated by only heating the rich-CO2 phase. In this work, amino acid ionic liquids (AAILs) were synthesized using quaternary ammonium salts and amino acids as raw materials, and the aqueous solutions were prepared as novel liquid-solid phase change solvents. The results showed that the solvents had excellent CO2 absorption capacity, and the AAILs functionalized by glycine and tryptophan exhibited significant phase change properties. The mechanism of phase-change of the solvent were mainly due to the lower solubility of the product after reaction between AAILs and CO2. The solvent with tryptophan as anion could be regenerated by only heating the CO2-riched solid phase, which might significantly decrease energy consumption of regeneration. And the absorbent could be reused with the regenerated absorption ratio up to 79%. The solvent system has great potential in industrial application due to the easy operation process and efficient recycling ability.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new antitrypanosomal compounds, we investigated the potential of metabolites from bacteria living in corals and sediments of the Southeastern Brazilian coast. Three corals Tubastraea coccinea, Mussismilia hispida, Madracis decactis and sediments yielded 11 bacterial strains, that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera - Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. Crude extracts showed IC50 values ranging from 15 to 51 μg/mL against trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using NMR and ESI-HRMS analysis, FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate these unsaturated iso-type fatty acids as possible new hits against T. cruzi.

A hybrid organic molecules as ligands and inorganic NCs in this research combines the chemical properties of organic semiconductors with the chemical stability of inor- ganic nanoparticles like PbS. It is possible to improve the ligand exchange and PbS-NCs' distribution by adding Amino phynel anchor group to TIPs-pentacene and Carboxylic anchor group to Tetraphenylporphyrin molecules. By adding anchor groups to one or two sides of these molecules, they would convert the molecules to ecient ligands to obtain superlattice coupled organic-inorganic nanostrcuture semicondcutor layers (COINs). Adding on side group would cap the PbS nanoparticles while adding two an- chor group would play a linker role between two PbS NCs. This morophology enhance- ment paves the way to manipulate the physical properties of the COINs and fabricate solar cells. Singlet ssion phenomena demonstrates pentacene molecule's advantage for high eciency in organic solar cells and its ability to overcome the Schockley-Queisser limit. Ultraviolet photo-emission spectroscopy (UPS) determines the highest occupied molecular orbital (HOMO) and the work function of COINs, while the lowest unoccu- pied molecular orbital (LUMO) of COINs were calculated subsequently by adding both the exciton binding energy and the optical band gap to the measured HOMO energy. The current versus voltage characteristics and impedance spectroscopy were studied for these molecules as well.

Several series of new polymers were synthesized: binary copolyesters of vanillic (VA) and hydroxybiphenylcarboxylic (HBCA) acids, as well as ternary copolyesters additionally containing hydroxybenzoic acid (HBA) and obtained via three different ways (in solution, in melt and in solid state). The high values of logarithmic intrinsic viscosities and insolubility of several samples proved its high molecular weights. It has been shown that the use of vanillic acid leads to the production of copolyesters with a relatively high glass transition temperature (about 130°C). Thermogravimetric analysis revealed onset of weight loss temperatures of ternary copolyesters occurred at 330-350 °C, the temperature of 5% mass loss is in the range of 390-410 °C. Two-stage thermal destruction is observed for all aromatic copolyester of vanillic acid: decomposition begins with VA units at 420-480 °C, and then decomposition of more heat-resistant units demonstrated above 520 °C. The copolyesters are thermotropic and exhibit a typical nematic type of liquid crystalline order. Mechanical characteristics of copolyesters are close to those for semi-aromatic copolyesters, but are much lower than typical values for fully aromatic thermotropic polymers. Thus, vanillic acid is a mesogenic monomer suitable for the synthesis of thermotropic fully aromatic and semi-aromatic copolyester, but resulting processing temperature must not exceed 280°C.

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans. Increasing data suggest that CVD is closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as biomarkers of CVD. For this objective, the evolution of the plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) was monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS²) in different rat models of CVD, i.e. angiotensin-II-induced hypertension (HTN), ischemic chronic heart failure (CHF) and sugen/hypoxia(SuHx)-induced pulmonary hypertension (PH). On one hand, there was modest changes on the monitored compounds in HTN (LPA 16:0, 18:1 and 20:4), LPC 16:1) and CHF (LPA 16:0, LPC 18:1 and LPE 16:0 and 18:0) models compared to control rats but these changes were no longer significant after correction for multiple testing. On the other hand, PH was associated with important changes in plasma LPA with a significant increase in the 16:0, 18:1, 18:2, 20:4 and 22:6 species. A deleterious impact of LPA was confirmed on isolated human pulmonary smooth muscle cells with an increase in their proliferation. This study demonstrates that circulating LPA species are increased in rats with PH and may contribute to the pathophysiology of this disease. Additional experiments are needed to assess whether the modulation of LPA signaling in PH may be of interest.

We synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids using an easy and short step synthetic route. All compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: GPR40, aldose reductase (AKR1B1), PPARγ and GLUT-4. Compound 1 displayed an EC₅₀ value of 0.075 μM against GPR40 and was an AKR1B1 inhibitor, showing IC₅₀ = 7.4 μM. Compounds 2 and 3 behave as AKR1B1 inhibitors, GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active compounds on these targets. Compounds 1-3 were tested in vivo at 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non insulin-dependent diabetes mellitus mice model. Compounds 2 and 3 showed robust in vitro and in vivo efficacy, and could be considered as promising multitarget antidiabetic drug candidates. This is the first report of a single molecule with these four polypharmacological target action.

Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P<0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P<0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P<0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

A label-free four-step procedure to identify amino acids (AAs) is described. In Step 1 molecules of AA, a tRNA, the related tRNA synthetase (AARS), and ATP are confined in a cavity to enable charging of tRNA. In Step 2 the tRNA, charged or uncharged, is separated from the other reactants (ATP, AARS, and possibly AMP and free AAs). In Step 3 the separated tRNA is subjected to non-enzymatic deacylation to dissociate the AA if tRNA is charged. In Step 4 the products are transferred to an electrolytic cell with a nanopore, where a current blockade occurs if and only if there is a dissociated AA. If a blockade is observed AA is immediately known, identification is unambiguous because of tRNA superspecificity. The exact blockade size need not be known (for any AA) in Step 4 so there is no need to distinguish among different AAs. This is unlike other nanopore-based methods, which are crucially dependent on precise blockade level measurements. The procedure is done in parallel with N (20 ≤ N ≤ 61) copies of AA, N reservoir-cavities, and N pairs of e-cells each with a different tRNA, related AARS, and ATP. At least one of the tRNAs gets charged. Assuming no charging errors, if N₁ tRNAs get charged in Step 1 and at least one of N₂ (≤ N₁) charged tRNAs is deacylated in Step 3, then with N₁N₂ tRNA molecules entering Step 1 AA can be identified with probability 1.

Inflammatory allergic and nonallergic respiratory pathologies often co-exist. The root cause is not clear. This paper demonstrates that it is ascribable to protons (H⁺) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation and bronchospasm; b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic responses. Therefore, the intracellular acidification and consequent Ca²⁺ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may be the causal mechanism of the multimorbidity of these diseases, and environmental acidity may contribute to their spread.

Understanding the implications of organic acids in animal diets on physiological markers is critical for developing viable strategies for improving overall health and performance. The aim of this study was to evaluate the influence of dietary organic acids inclusion on rabbits’ growth performance and physiological status by determining blood and intestine development indicators. Forty weaned rabbits aged 28-d randomly assigned into 2 groups and fed with standard compound diet (SCD) and SCD + 0.2% organic acids mixture (butyric, propionic, sorbic; OAM). Growth performance was evaluated between 28-77 d of age, physiological status at 77 d of age. OAM’s rabbits final body weight, ADG, DFI, growth rate indicators were higher, but FCR lower compared to SCD (P < 0.05). OAM increased total protein and albumin levels in blood plasma; reduced pH, increased DM, achieved greater viscosity in caecum’s content (P < 0.05). Compared to SCD better gut development observed in OAM, as total intestinal weight was significantly higher (P < 0.05). Acetic and propionic acids concentrations were increased, but butyric reduced in OAM caecum’s content (P < 0.05). OAM had significant effect on the most caecum histomorphometric parameters: increased villus height, crypt depth and their ratio (P < 0.05). According to our results OAM can improve rabbits’ growth performance, nutrient intake, and feed digestibility by significantly improving physiological status.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

The lipid fraction of margarines and fast-food French-fries, two types of foods traditionally high in trans fatty acids (TFA), is assessed. TFA data reported worldwide during the last 20 years have been gathered, and show that some countries still report high TFA amounts in these products. The content of TFA was analysed in margarines (2 store and 4 premium brands) and French-fries from fast-food restaurants (5 chains). Margarines showed mean values of 0.68% and 0.43% (gTFA/100g fat) for store and premium brands, respectively. French-fries values ranged from 0.49% to 0.89%. All samples were lower than the 2% set by some European countries as the maximum legal content of TFA in fats, and contained less than 0.5g/serving, so they could also be considered “trans free products”. This work confirmed that the presence of TFA is not significant in the two analysed products and contributes to update food composition tables, key tools for epidemiological and nutrition studies.

This work attempted to fabricate superhydrophobic fabric via simple immersion technique. Textile fabrics were coated with silica nanoparticles prepared from tetraethoxysilane (TEOS) to obtain sufficient roughness with hydrophobic surface chemistry. Then the coated fabrics were treated with polydimethylsiloxane (PDMS) and aminopropyltriethoxysilane (APTES) to reduce the surface energy. The effects of PDMS concentration on the surface morphology and superhydrophobicity of as-prepared fabric were investigated. The morphology and the composition of superhydrophobic fabric was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDS) and Fourier transform infrared (FTIR) spectroscopy. The results revealed the formation of spherical silica nanoparticles with average particle size of 250 nm throughout the fabric surface. The possible interactions between silica nanoparticles and APTES, as well as the fabrics were elucidated. Investigating the hydrophobicity of fabrics via water contact angle (WCA) measurement showed that the treated fabric exhibits excellent water repellency with a water contact angle as high as 151° and a very low water sliding angle. It also found that the treated fabric maintained most of its hydrophobicity against repeated washing. The comfort properties of the obtained superhydrophobic fabrics in term of air permeability and bending length did not reveal any significant changes.

There is a great interest in finding antioxidants and products with antimicrobial activities from natural sources. The aim of this study was to obtain and identify the phenolic components and organic acids from Camellia oleifera cake. In addition, their antioxidant and antimicrobial activities were also investigated. The purity of phenolic components and organic acids obtained were 94.1 ± 0.5% w/w and 96.0 ± 0.3% w/w, respectively. There are 15 phenolic components have been detected and identified by HPLC-ESI-MS. Oxalic, citric, acetic, malic, and succinic acids are found to be major organic acids. The phenolic components and organic acids both had good antioxidant capacity, evaluated by 4 antioxidant activity assays (hydroxyl radical scavenging, superoxide radical scavenging, 1,1-diphenyl-2-picryl-hydrazyl radical scavenging and lipid peroxidation inhibition). In addition, the phenolic components and organic acids exhibited significant inhibitory activity against bacteria Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and fungi Mucor racemosus, Aspergillus oryzae, Rhizopus stolonifer. The phenolic components and organic acids from C. oleifera cake both showed good antioxidant capacity and exhibited antimicrobial activities. These results may be useful for the future use of phenolic components and organic acids from C. oleifera cake.

Recent developments in artificial nucleic acid and drug delivery systems (DDS) present possibilities for the symbiotic engineering of oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs), and small interfering RNA (siRNA). These technologies can also be applied for triplex-forming oligonucleotides (TFOs) to develop symbiotic genome-targeting tools and a new class of oligonucleotide drugs. Many reports have described the functionalization of TFOs and the enhancement of TFO activities. In particular, the tethering of crosslinking groups to TFOs enables irreversible triplex formation and is frequently exploited for antigene and genome-editing experiments. These crosslinkable TFOs have shown considerable potential for therapeutic application. In this review, we revisit these crosslinking techniques and explore the combination of these techniques with recent artificial oligonucleotide and DDS technologies.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Alzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupt the signal transduction in neurons and other glia cells. The pathological protein Tau and amyloid-β contributes to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-beta in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. PI 3, 4, 5-P3 involves in phagocytic cup formation and relates actin remodeling whereas PI 4, 5-P2-mediates the process of phagosomes formation and further fusion with early endosome. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. Dietary fatty acids depending on their ratio and types of intake influence secondary lipid messenger along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The deposited Aβ deposits and extracellular Tau seed disrupt levels of phosphatidylinositol and actin cytoskeletal changes that hamper microglia signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. We keen to understand different types of phosphatidylinositol species levels in signaling events such as phagocytosis and actin remodeling owing to the exposure of various types of dietary fatty acids.

Newly designed pentacyclic benzimidazole derivatives, featuring amino or amido side chains, were synthesized to assess their in vitro antiproliferative activity. Additionally, we conducted investigations into their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were synthesized using conventional organic synthesis methodologies, alongside photochemical and microwave-assisted reactions. Upon synthesis, the newly derived compounds underwent in vitro testing for their antiproliferative effects on various human cancer cell lines. Notably, derivatives 6 and 9 exhibited significant antiproliferative activity within the submicromolar concentration range. Our biological assessment highlighted that the biological activity was strongly influenced by both the position of the N atom on the quinoline moiety and the position and nature of the side chain on the pentacyclic skeleton. Findings from fluorescence, circular dichroism spectroscopy, and thermal melting assays indicated a mixed binding mode—comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone—of these pentacyclic benzimidazoles with DNA and RNA.

Benzazoles, such as benzoxazoles and benzothiazoles, are compounds with important biological and pharmacological activities and important intermediaries in synthesis. This report presents a linear synthesis of a butanamide derived from linking 5-chloro-2-aminobenzoxazole and 2-aminobenzothiazole via 4-chlorobutanoyl chloride. The corresponding compound N-(benzothiazol-2-yl)-4-((5-chlorobenzoxazol-2-yl)aminobutanamide was obtained in good [PVG1] yield using accessible starting materials and methodology in two reaction steps. Furthermore, we made docking studies of this compound on 3-TOP protein to explore its potential as an antidiabetic agent with an excellent yield.

We designed a novel growth controller regulated by feeding of an unnatural amino acid, Nε-benzyloxycarbonyl-L-lysine (ZK), using a specific incorporation system at a sense codon. This system is constructed by a pair of modified pyrrolisyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl). Although ZK is non-toxic for normal organisms, the growth of Escherichia coli carrying the ZK incorporation system was inhibited in a ZK concentration-dependent manner without causing rapid bacterial death, presumably due to generation of non-functional or toxic proteins. The extent of growth inhibition strongly depended on the anticodon sequence of the tRNApyl gene. Taking advantage of the low selectivity of PylRS for tRNApyl anticodons, we experimentally determined the most effective anticodon sequence among all 64 nucleotide sequences in the anticodon region of tRNApyl gene. The results suggest that the ZK-regulated growth controller is a simple, target-specific, environmental noise-resistant and titratable system. This technique may be applicable to a wide variety of organisms because the growth inhibitory effects are caused by “informational disturbance”, in which the highly conserved system for transmission of information from DNA to proteins is perturbed.

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this study was to further evaluate the influence of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38±15 years/age and 7 females at 34±18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 grams of EAAS twice/day (BID)) or high dose (HD: 13 grams of EAAS BID). Both groups consumed the supplement for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual energy x-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at P<0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p=0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407±141 ng/ml and HD at 429±196 ng/ml, indicating chronic and excess alcohol consumption. Based on these results, we conclude that 13 grams of proprietary EAAS consumed BID lowers IHL in individuals with mild to moderate AUD.

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

Chiral hydroxamic acid (HA) and bis-hydroxamic acid (BHA) ligands have made significant contributions to the field of asymmetric synthesis, particularly in the synthesis of natural products. These ligands possess unique molecular structures that allow for exceptional stereochemical control, leading to their widespread use in catalytic systems. This review highlights the advancements made in asymmetric synthesis using chiral hydroxamic acid and bis-hydroxamic acid ligands and their impact on the synthesis of complex natural products. The discussion encompasses their role in enantioselective C-C bond formation, the functionalization of C-H bonds, asymmetric transformations involving heteroatoms, and their application in the total synthesis of natural products. The versatility and efficiency of chiral hydroxamic acid ligands and bis-hydroxamic acid ligands make them invaluable tools for synthetic chemists working towards the efficient and selective synthesis of natural products. This review provides a comprehensive overview of their contributions, showcasing their potential to expand the boundaries of chemical synthesis and access the diverse array of natural product scaffolds.

Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biological relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition to triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl and disulfane functional groups and pyridine-derived disulfides have been obtained from bis and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found.

In recent years, nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) has become a leading worldwide disease, and its therapies are facing many complexities. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear receptor (NR) superfamily and have three subtypes: PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). They have been identified to be essential in the regulation of lipid metabolism by controlling the transcription of genes related to fatty acids, bile acids, and cholesterol metabolism. Many PPAR agonists have been reported, such as natural agonists (fatty acids, eicosanoids, and phospholipids) and synthetic ligands (fibrates, thiazolidinediones, glitazars, and elafibranor). PPAR-based chemicals have a breakthrough in the innovation of therapy for fatty liver disease. This review will provide an overview of how PPARα and PPARγ play roles in lipid homeostasis, discussing the consideration of their agonists as potential therapeutic agents for NAFLD/NASH.

The absorption of medium-chain fatty acids (MCFA) depends on the solubility of these components in the gastric fluid. Parameters such as the total MCFA concentration, carboxyl ionization level, and carbon chain length affect the solubility of these molecules. Moreover, the enzymatic lipolysis of solubilized triacylglycerol (TAG) molecules may depend on the carbon chain length of the fatty acids (FAs) components and their positions on the glycerol backbone. This present study aimed at investigating the effect of electrolyte usually formed during the gastric digestion phase on the solubility of MCFA, and evaluating the influence of the FA carbon chain length on the lipolysis rate during the in vitro digestion simulation. The results obtained here showed that the increasing of electrolyte concentrations tend to decrease the mutual solubility of systems composed by the caproic and caprylic fatty acids + sodium chloride, sodium bicarbonate, and potassium chloride solutions. We also observed that a conventional version of the thermodynamic UNIQUAC model was able to correlate the liquid-liquid phase behavior of the electrolyte solutions. Regarding the in vitro digestion simulation, the experimental data indicated that the action of the pancreatic enzyme occurred preferentially in TAG molecules comprised of short and medium-chain fatty acids.

The C5-methylation of uracil to form 5-methyluracil (m⁵U) is a ubiquitous base modification of nucleic acids. Four enzyme families have converged to catalyze this methylation using different chemical solutions. Here, we investigate the evolution of 5-methyluracil synthase families in Mollicutes, a class of bacteria that has undergone extensive genome erosion. Many mollicutes have lost some of the m⁵U methyltransferases present in their common ancestor. Cases of duplication and subsequent shift of function are also described. For example, most members of the Spiroplasma subgroup, use the ancestral tetrahydrofolate-dependent TrmFO enzyme, to catalyze the formation of m⁵U54 in tRNA, while a TrmFO paralog (termed RlmFO) is responsible for m⁵U1939 formation in 23S RNA. RlmFO has replaced the S-adenosyl-l-methionine (SAM)-enzyme RlmD that adds the same modification in the ancestor and which is still present in mollicutes from the Hominis subgroup. Another paralog of this family, the TrmFO-like protein, has a yet unidentified function that differs from the TrmFO and RlmFO homologs. Despite having evolved towards minimal genomes, the mollicutes possess a repertoire of m⁵U modifying enzymes that is highly dynamic and has undergone horizontal transfer. This emphasizes the necessity for combining bioinformatics predictions with empirical testing and structural information to get a reliable functional annotation of these enzymes.

Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

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.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

In this study dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

The increasing demand for high-quality livestock products dictates to develop approaches to assessing the composition of the fatty acids (CFAs) and amino acids (CAAs) in animal tissues. The review considers the following issues: chromatographic methods for the determination of CAAs and CFAs of pig tissues; factors influencing the CAAs and CFAs of pig tissues; methods of regulating CAAs and CFAs of pork using nutritional factors; the effect of CAAs and CFAs on formation of meat properties. The main methods for determining CAAs or CFAs are the ion-exchange or gas chromatography, respectively. The total FA amount and individual FAs have significant effects on the tenderness, taste, color and juiciness of pork meat (due to the different melting points of particular fatty acids, formation of lipid oxidation products during cooking, etc.). Muscle proteins of pigs with regulated fatness differ also in CAAs (decreasing by increase in “pork fat” and decrease in the protein’s amount. The significance of this review is also determined by high popularity of pork in Russia and in a number of other countries of the world.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

In this study, we successfully synthesized a novel branched polyamide 6 with ε-caprolactam(CPL) and α-Amino-ε-caprolactam(ACL) through hydrolytic ring-open co-polymerization. The NMR characterization and rheological test result proved the existence of branched chain structure additionally. The branched chain structure caused a remarkable enhancement in the rheological properties. The met index(MFR),zero shear rate viscosity and storage modulus at low frequency region had a remarkable increase.The shear thinning phenomenon became more obvious. The thermal properties test determined by differential scanning calorimetry(DSC) showed that the melting point and crystallinity of co-polymers decreased with the increase of ACL addition.However, the crystal structure of the samples remained unchanged. The appropriate addition amount of ACL can improve the tensile mechanical properties of the co-polymers. When the amount of ACL was 1%, the tensile strength and fracture elongation rate of the co-polymers had the most significant increase.

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (nuclear magnetic resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine (F.C. = 0.8, p = 0.002), lysine (FC = 0.8, p &lt; 0.001), leucine (FC=0.7, p &lt; 0.001) but higher levels of formic acid (FC=1.6, p ≤ 0.001) when compared to controls. However, metabolic profiling of MM patients compared to controls exhibited decreased levels of total Apolipoprotein-A1 (FC =0.6, p&lt;0.001), HDL-4 Apolipoprotein-A1 (FC = 0.5, p ≤ 0.001), HDL-4 Apolipoprotein-A2 (FC = 0.6, p &lt; 0.001), HDL Free Cholesterol (FC = 0.7, p &lt; 0.001), HDL-3 Cholesterol (FC = 0.5, p ≤ 0.001) and HDL-4 Cholesterol (FC = 0.5, p ≤ 0.001). Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol (FC = 0.6, p ≤ 0.001), HDL Cholesterol (FC = 0.7, p ≤ 0.001), HDL Free Cholesterol (FC = 0.4, p ≤ 0.001), Total Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL-4 Apolipoprotein-A1 (FC = 0.6, p ≤ 0.001) and HDL-4 Phospholipids (FC = 0.6, p ≤ 0.001). This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, Wuhan coronavirus (COVID-19), plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms were stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission and cure RNA virus infection were proposed, implying that FIR radiation might be a cheap, convenient, and efficient method in clinic to treat RNA virus.

Increasing pesticide resistance in plant pathogens is major concern in agriculture production. Research on ecofriendly alternatives of chemical pesticides are more in demand in pesticide industry. In the current study, an ethyl acetate extract from the endophytic fungus Trichoderma sp. EFI 671, isolated from the stem parts of the medicinal plant Laurus sp., was screened for bioactivity against plant pathogens (Fusarium graminearum, Rhizoctonia solani, Sclerotinia sclerotiorum and Botrytis cinerea), insect pests (Spodoptera littoralis, Myzus persicae, Rhopalosiphum padi) and plant parasites (Meloidogyne javanica). The bioactive components have been characterized following a bioassay-guided isolation against M. persicae. The chemical study of this bioactive extract resulted in the isolation of 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (1), eburicol (2), (24R)-stigmast-4-ene-3-one or β-sitostenone (3), ergosterol (4) and ergosterol peroxide (5). The free fatty acids present in compound 1 (oleic, linoleic and palmitic) showed strong dose-dependent aphid antifeedant effects against M. persicae. Liquid (PDB, and SDB) and solid (corn, sorghum, pearl millet and rice) growth media were tested in order to optimize the yield and bioactivity of the fungal extracts. Pearl millet and corn gave the highest extract yields. All the extracts from these solid media had strong effects against M. persicae with sorghum being the most active. Corn increased the content in linolenic, pearl millet the oleic and stearic and sorghum oleic and linolenic acids compared to rice. Their antifeedant effects correlated with linoleic /oleic acids. The phytotoxic effects of these extracts against Lolium perenne and Lactuca sativa varied with culture media, with sorghum being the least toxic.

The fatty-acid profiles of five main commercial pistachio cultivars, including Ahmad-Aghaei, Akbari, Chrok, Kalle-Ghouchi and Ohadi, were determined by gas chromatography: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), linolenic (C18:3) arachidic (C20:0) and gondoic (C20:1) acid. Based on the oleic to linoleic acid (O/L) ratio, a quality index was determined for these five cultivars: Ohadi (2.40) < Ahmad-Aghaei (2.60) < Kale-Ghouchi (2.94) < Chrok (3.05) < Akbari (3.66). Principal component analysis (PCA) of the fatty-acid data yielded three significant PCs, which together account for 80.0% of the total variance in the data set. A linear discriminant analysis (LDA) model evaluated with cross validation correctly classified almost all samples: the average percent accuracy for the prediction set was 98.0%. The high predictive power for the prediction set shows the ability to indicate the cultivar of an unknown sample based on its fatty-acid chromatographic fingerprint.

Volatile fatty acids (VFAs) are a group of common metabolites with a potential of universal infochemicals dedicated to transferring of information between higher organisms and bacteria either from microbiome or external environment. VFAs are common substances among various insect orders, there are numerous studies exploring their influence on the behavior of different insect species. In relation to papers published by J. E. McFarlane, we assess the effects of formic, acetic, propionic, butyric, valeric acids on spatial preference of common stored food grain products, and poultry industry pest – lesser mealworm (Alphitobius diaperinus). We present novel method of continuous, simultaneous assessment of site preference as well as travelled distance in constant-flow olfactometer. All tested VFAs except valeric had a significant repellent effect with formic acid being effective in the lowest concentration. Additionally, VFAs significantly altered distance travelled by insects. Obtained results indicate a potential role of VFAs in the olfactory guided behavior of A. diaperinus, we speculate that reaction to the presence if VFAs may deviate form specificity of species’ original habitat.

The interactions of metal ions with fulvic acids resulted in changes in the particle size and charge. Particle size distribution was trimodal for fulvic acids, bimodal for fulvic complexes with calcium and magnesium, and copper-fulvic complexes had only one size fraction. The compensation of negative charge of carboxylic and phenolic functional groups by positive charged metal ions resulted in the increase in zeta potential which was getting closer to zero in the case of copper-fulvic complexes. However, all metal humic complexes behaved as colloidally unstable which resulted in visually observable sedimentation. Calorimetric measurements provided positive values of changes in enthalpy which indicated endothermic processes. In contrast quantum chemical calculations as well as experiments with model compounds provided negative values indicated exothermic processes. Changes in Gibbs energy were determined as negative and changes in entropy as positive which meant spontaneous processes.

The objective of this study was to investigate the umami characteristics of soy sauce using electronic tongue evaluation and amino acid composition and Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. The soy sauce peptides were isolated from soy sauce using XAD-16 macroporous resin combined with ethanol solution. Results showed that the soy sauce peptide fraction eluted by 60% ethanol (SS-60%) exhibited a prominent umami taste and the umami scores were highly positively correlated with the amino acid nitrogen contents of soy sauces. The umami scores of SS-60% were significantly positively correlated with the contents of free amino acids. Especially, Phe showed the highest positive correlation with the umami scores. In addition, five characteristic ion peaks with m/z at 499, 561, 643, 649, and 855 were identified in the peptide mass fingerprinting. Therefore, this study provides new insights into the umami characteristics for the flavor evaluation and reality identification of soy sauce.

Peptides of hydrolysates of food proteins are an easily digestible source of amino acids necessary for the body to adapt to physical stress. Commercially significant hydrolysates include whey protein, casein, and other animal proteins. Hydrolysates of plant proteins are gaining popularity, but they are less common, then animal ones. Soy protein isolate is promising for obtaining the hydrolysates due to its affordable price and balanced amino acid profile. However, there are no direct studies showing an improvement in the result of physical activity when eating soy protein isolate hydrolysate (SPIH). In this work, for the first time, the study was conducted on the safety and efficacy of SPIH during physical load on model animals (rats). It was shown that the hydrolysate did not lead to pathological changes in the viscera, food intake, and weight of animals did not differ from the control group (animals consumed whey protein). Under physical load rats enteral fed SPIH showed a tendency to adapt more quickly to physical stress than the control group and the group of animals that was fed by free amino acids. The metabolites of animal blood serum were studied by NMR spectroscopy. It was shown that by the 95th minute after feeding in the group of rats receiving SPIH, the difference of proteinogenic amino acids concentrations in blood between individuals was significantly less than in the groups receiving whey protein or a mixture of amino acids. In other words, individual biochemical and physiological characteristics of individuals did not affect the assimilation of amino acids of hydrolysate.