Molecular interaction between three novel amino acid based deep eutectic solvents with surface active ionic liquid: A comparative study.

Interaction between a surface active ionic liquid (IL) viz. 1-decyl-3-methylimidazolium chloride [Dmim][Cl] with three novel amino acid-based deep eutectic solvents (DES, consisting of choline chloride and l-methionine (DES1), l-phenylalanine (DES2), and l-glutamine (DES3) in a 1: 2 mol ratio) is studied. Several techniques, including surface tension, fluorescence, UV-visible spectroscopy, and Fourier transform infrared (FTIR), were used to investigate the key micellar properties and intermolecular interactions between the IL and DESs. All the DESs studied here facilitate the micellization process successfully lowering the critical micelle concentrations (CMC) of [Dmim][Cl] with addition of 5 wt% and 10 wt% of DESs. In decreasing order of DES2 > DES1 > DES3, the affinity to promote IL [Dmim][Cl] aggregation within aqueous DES solutions. Additionally, the CMC values as well as the surface tension at CMC are both noticeably reduced significantly by DES2. The surface tension method determines how three amino acid-based DESs affect the CMC, Гmax, πCMC, Amin and pC20 of micellization. When IL [Dmim][Cl] forms micelles within DES solutions, the solvophobic effect predominates, and the intermolecular hydrogen-bond interaction helps to form micelles. FTIR was used to examine the molecular interactions and structural changes of the ionic liquid self-assemblies in aqueous DESs. The results show that the presence of DESs greatly aids in the micellization of [Dmim][Cl], and to a greater extent for DES2 than for DES1/DES3. The colloidal properties of DES and their mixtures are advantageous for the solubility, micellization, and other features of ionic liquids; further details on this positive observation are provided in the results and discussion. In the areas of micellization, CMC, synthesis, catalysis, and environmental, biological, and pharmaceutical applications, among others, DESs are extremely useful.

Absence of PNET formation and normal longevity in a mouse model of Mahvash disease.

Mahvash disease, a rare autosomal recessive metabolic disorder characterized by biallelic loss-of-function mutations in the glucagon receptor gene (GCGR), induces significant pancreatic hyperglucagonemia, resulting in α-cell hyperplasia and occasional hypoglycemia. Utilizing CRISPR-Cas9 technology, we engineered a mouse model, designated as Gcgr V369M/V369M, harboring a homozygous V369M substitution in the glucagon receptor (GCGR). Although wild-type (WT) and Gcgr V369M/V369M mice exhibited no discernible difference in appearance or weight, adult Gcgr V369M/V369M mice, approximately 12 months of age, displayed a notable decrease in fasting blood glucose levels and elevated the levels of cholesterol and low-density lipoprotein-cholesterol. Moreover, plasma amino acid levels such as alanine (Ala), proline (Pro) and arginine (Arg) were elevated in Gcgr V369M/V369M mice contributing to α-cell proliferation and hyperglucagonemia. Despite sustained α-cell hyperplasia and increased circulating glucagon levels in Gcgr V369M/V369M mice, metabolic disparities between the two groups gradually waned with age accompanied by a reduction in α-cell hyperplasia. Throughout the lifespan of the mice (up to approximately 30 months), pancreatic neuroendocrine tumors (PNETs) did not manifest. This prolonged observation of metabolic alterations in Gcgr V369M/V369M mice furnishes valuable insights for a deeper comprehension of mild Mahvash disease in humans.

Environment-dependent chlorophyll-chlorophyll charge transfer states in Lhca4 pigment-protein complex.

Photosystem I (PSI) light-harvesting antenna complexes LHCI contain spectral forms that absorb and emit photons of lower energy than that of its primary electron donor, P700. The most red-shifted fluorescence is associated with the Lhca4 complex. It has been suggested that this red emission is related to the inter-chlorophyll charge transfer (CT) states. In this work we present a systematic quantum-chemical study of the CT states in Lhca4, accounting for the influence of the protein environment by estimating the electrostatic interactions. We show that significant energy shifts result from these interactions and propose that the emission of the Lhca4 complex is related not only to the previously proposed a603+-a608- state, but also to the a602+-a603- state. We also investigate how different protonation patterns of protein amino acids affect the energetics of the CT states.

"Three-dimensional environment-friendly" amino acid functionalized chitosan: Uranium adsorption performance and mechanism research.

To achieve the goals of "carbon peak and carbon neutrality" and sustainable development, we propose "Three-Dimensional Environment-Friendly" materials to balance the urgent need for the development of clean energy and the reduction of secondary environmental pollution during adsorbent preparation. In this study, three novel chitosan adsorbents (CMNSC-Leu, CMNSC-Pro, CMNSC-Phe) for uranium adsorption were designed on the basis of molecular level and successfully synthesized with three different amino acids (leucine, proline, phenylalanine) through amidation reaction in an aqueous environment using a sustainable green chitosan material. The uranium adsorption capacity of the three adsorbents was evaluated by batch adsorption, selectivity and recyclability studies. The adsorption reaction conformed to the pseudo-second-order model and was a spontaneous endothermic reaction. In particular, the maximum adsorption capacity of CMNSC-Pro for uranium was 462.7 mg·g-1 at C0 = 100 ppm. In addition, CMNSC-Pro showed better selectivity and good reusability. DFT calculation and IRI diagram were applied in this work to analyze the unique structure and adsorption process of CMNSC-Pro from the perspective of structure. Uranium was adsorbed by CMNSC-Pro via coordination, electrostatic interaction, and intraparticle diffusion. This work provided a new idea for the structural design and construction of new high-efficiency biomass adsorbents.

Plant proteins, peptides, and non-protein amino acids: Toxicity, sources, and analysis.

Plants have evolved various mechanisms to synthesize diverse range of substances that contribute to their survival against pests, pathogens, predators, and adverse environmental conditions. Although several plant metabolites possess therapeutic potential, some can be potentially harmful to human and animal health when consumed in large proportion. Proteins, peptides, and non-protein amino acids are products of plant biochemical pathways with proven beneficial and nutritional effects. Despite these benefits, the in vivo toxicities associated with certain plant-derived proteins, peptides, and non-protein amino acids pose a significant risk to humans and animals. Symptoms of poisoning include nausea, vomiting, diarrhea, hair and weight loss, goiter, cataracts, and infertility. Even though plant processing methods such as soaking and drying can reduce the amount of toxin contained in plants, complete riddance is often impossible. As such, food regulatory bodies need to prevent uncontrolled consumption of the listed and many other toxin-containing plant species to keep the public safe. For this purpose, this review collates crucial insights into the sources, and in vivo toxicity associated with certain plant-derived proteins, peptides, and non-protein amino acids that have the clear potential to adversely affect human health. Additionally, this review provides information on analytical methods suitable for the detection of these substances in plants.

Amino acid surface modified bioglass: A candidate biomaterial for bone tissue engineering1.

Bioglasses are solid materials consisted of sodium oxide, calcium oxide, silicon dioxide and phosphorus in various proportions and have used in bone tissue engineering. There have been ongoing efforts to improve the surface properties of bioglasses to increase biocompatibility and performance. The aim of the present study is to modify the bioglass surface with an amino acid mixture consisting of arginine, aspartic acid, phenylalanine, cysteine, histidine and lysine, to characterize the surface, and to evaluate the performance and biocompatibility in vitro and in vivo. The untreated bioglass, bioglass kept in simulated body fluid (SBF), and modified bioglass were used in further evaluation. After confirmation of the surface modification with FT-IR analyses and SEM analyses, MC3T3-E1 preosteoblasts adhesion on the surface was also revealed by SEM. The modified bioglass had significantly higher ALP activity in colorimetric measurement, rate of calcium accumulations in Alizarin red s staining, lower rate of cell death in Annexin-V/PI staining to determine apoptosis and necrosis. Having higher cell viability rate in MTT test and absence of genotoxicity in micronucleus test (OECD 487), the modified bioglass was further confirmed for biocompatibility in vitro. The results of the rat tibial defect model revealed that the all bioglass treatments had a significantly better bone healing score compared to the untreated negative control. However, the modified bioglass exhibited significantly better bone healing efforts especially during the first and the second months compared to the other bioglass treatment treatments. As a result, the amino acid surface modification of bioglasses improves the surface biocompatibility and osteogenic performance that makes the amino acid modified bioglass a better candidate for bone tissue engineering. RESEARCH HIGHLIGHTS: Bioglass surface modification with amino acids contributes to bioglass-tissue interaction with an improved cell attachment. Modified bioglass increases in vitro Alp activity and calcium accumulation, and also positively affects cell behavior by supporting cell adaptation. Bioglass exerts osteogenic potential in vivo especially during early bone healing.

Phylogenetic analysis of Staphylococcus aureus enterotoxin A gene in Iraqi breed cows with bovine mastitis: Implications for disease management.

Background: Although milk is nutritionally valuable, it also serves as a significant medium for the transmission of pathogens and their toxins. Aim: This study aimed to investigate the role of enterotoxin gene A (SEA) in the development of bovine mastitis. We accomplished this by examining milk through polymerase chain reaction (PCR) testing, amino acid substitution analysis, and phylogenetic analysis. Methods: A total of fifty milk samples were collected from locally bred dairy cows in Al-Diwaniyah, located in southern Iraq. We employed the VITEK-2 platform to validate the diagnosis of Staphylococcus aureus and confirm the results of routine tests (culturing and biochemical tests). Subsequently, the genetic mutation and phylogeny analysis were achieved utilizing DNA sequencing to 16S rRNA and enterotoxin A genes. Results: 66% (33/50) of the milk samples found to be contain S. aureus by the VITEK-2 system. Furthermore, 25/33 of the samples were positive by the PCR test. While 60% (15 out of 25) tested positive for the SEA gene. After genomic analysis, we identified amino acid substitutions of serine, glutamine with arginine, tyrosine with cysteine, and aspartic acid with glycine at positions 9, 101, 119, 187, and 191. The phylogenetic investigation demonstrated a genetic relationship between our isolates (Iraqi isolates) and isolates from Indian and the United States. Conclusion: Our study indicated the widespread distribution of the enterotoxin gene A (SEA) of S. aureus among dairy cows. The molecular study revealed significant changes in key amino acids that could play an important role in the bacterium's pathogenesis. The phylogenetic similarities among S. aureus samples from various countries suggest that the bacteria has spread globally.

Genomic signatures of cold adaptation in the family Colwelliaceae.

Psychrophily is a phenotype describing microbial growth at low temperatures; elucidating the biomolecular and genomic adaptations necessary for survival in the cold is important for understanding life in extreme environments on Earth and in outer space. We used comparative genomics and temperature growth experiments of bacteria from the family Colwelliaceae to identify genomic factors correlated with optimal growth temperature (OGT). A phylogenomic analysis of 67 public and 39 newly sequenced strains revealed three main clades of Colwelliaceae. Temperature growth experiments revealed significant differences in mean OGT by clade, wherein strains of Colwelliaceae had similar growth rates at -1 °C but varied in their ability to tolerate 17 °C. Using amino acid compositional indices, a multiple linear regression model was constructed to predict the OGT of these organisms (RMSE 5.2 °C). Investigation of Colwelliaceae functional genes revealed a putative cold-adaptive gene cassette that was present in psychrophilic strains but absent in a closely related strain with a significantly higher OGT. This study also presents genomic evidence suggesting that the clade of Colwelliaceae containing Colwellia hornerae should be investigated as a new genus. These contributions offer key insights into the psychrophily phenotype and its underlying genomic foundation in the family Colwelliaceae.

Coinoculation of autochthonous starter cultures: A strategy to improve the flavor characteristics and inhibit biogenic amines of Harbin dry sausage.

The effects of separately coinoculating Lactiplantibacillus plantarum S8 (LP) with Staphylococcus carnosus L8 (LP + SC), Pichia kudriavzevii M6 (LP + PK), and S. carnosus L8 and P. kudriavzevii M6 (LP + SC + PK) on the flavor characteristics and biogenic amines (BAs) production in Harbin dry sausages were investigated. The coinoculated sausages exhibited higher free amino acids (FAAs) content than the noninoculated and LP sausages. Moreover, inoculated dry sausages exhibited lower BA contents (174.45, 239.43, 190.24, and 206.7 mg/kg for the LP, LP + SC, LP + PK, and LP + PK + SC sausages, respectively) than the noninoculated sausage (339.73 mg/kg). Meanwhile, the LP + PK and LP + SC + PK sausages had the highest contents of esters (996.70 µg/kg) and alcohols (603.46 µg/kg), respectively. A sensory evaluation demonstrated that the LP + SC + PK sausage had the highest fermented odor and the lowest fatty odor. Pearson correlation analysis revealed that FAAs were correlated with most key volatile compounds and BAs. This study provides new insights into flavor development and BA inhibition in dry sausages through coinoculation.

Cryo-EM structure of ACE2-SIT1 in complex with Tiagabine.

The pharmacology of amino acid transporters in the SLC6 family is poorly developed compared to that of the neurotransmitter transporters. To identify new inhibitors of the proline transporter SIT1 (SLC6A20), its expression in Xenopus laevis oocytes was optimized. Trafficking of SIT1 was augmented by co-expression of angiotensin-converting enzyme 2 (ACE2) in oocytes but there was no strict requirement for co-expression of ACE2. A pharmacophore-guided screen identified tiagabine as a potent non-competitive inhibitor of SIT1. To understand its binding mode, we determined the cryo-electron microscopy (cryo-EM) structure of ACE2-SIT1 bound with tiagabine. The inhibitor binds close to the orthosteric proline binding site, but due to its size extends into the cytosolic vestibule. This causes the transporter to adopt an inward-open conformation, in which the intracellular gate is blocked. This study provides the first structural insight into inhibition of SIT1 and generates tools for a better understanding of the ACE2-SIT1 complex. These findings may have significance for SARS-CoV-2 binding to its receptor ACE2 in human lung alveolar cells where SIT1 and ACE2 are functionally expressed.

RBPs: an RNA editor's choice.

RNA-binding proteins (RBPs) play a key role in gene expression and post-transcriptional RNA regulation. As integral components of ribonucleoprotein complexes, RBPs are susceptible to genomic and RNA Editing derived amino acid substitutions, impacting functional interactions. This article explores the prevalent RNA Editing of RBPs, unravelling the complex interplay between RBPs and RNA Editing events. Emphasis is placed on their influence on single amino acid variants (SAAVs) and implications for disease development. The role of Proteogenomics in identifying SAAVs is briefly discussed, offering insights into the RBP landscape. RNA Editing within RBPs emerges as a promising target for precision medicine, reshaping our understanding of genetic and epigenetic variations in health and disease.

Biological features and quality comprehensive analysis of twelve germplasm resources of the genus Allium from Tibet.

Introduction: Allium is important vegetables and seasonings in China, Tibet is rich in unique resources of the genus Allium, but lacks development and utilization. Methods: We compared the biological features and comprehensively evaluating the quality of twelve germplasm resources of the genus Allium collected from Tibet. Results: The results revealed that nine germplasm resources were bolting and bloom normally except for SC015, SC019, and SC048, all twelve germplasm resources were able to vegetative growth. The individual differences in moisture, soluble sugar, and protein content among the twelve germplasm resources were relatively small, with pyruvic acid content ranging from 0.11 to 1.12 mg/g and a large variation coefficient. A total of 8 categories and 97 volatile compounds were detected in twelve germplasm resources, the majority possessed the highest proportions of aldehydes and organosulfur compounds, but there were certain differences between the different Allium species. Additionally, 11 to 16 types of free amino acids were present in all germplasm resources, proline exhibited the highest content. The total content of essential and non-essential amino acids in SC009 was the highest. Carbon (C) accounted for the largest proportion of all elements, and the contents of other mineral elements varied greatly among the different plants. Conclusion: In conclusion, combined with biological performance and comprehensive evaluation of quality, SC009 is the excellent germplasm resource suitable for growth and capable of reproduction with good quality. These results improved the exploitation and utilization of the genus Allium in Tibet, as well as provided germplasm resources for high-quality breeding of the genus Allium.

L-Cysteine: A promising nutritional supplement for alleviating anxiety disorders.

Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases.

Tuning the Functionality of Designer Translating Organelles with Orthogonal tRNA Synthetase/tRNA Pairs.

Site-specific incorporation of noncanonical amino acids (ncAAs) can be realized by genetic code expansion (GCE) technology. Different orthogonal tRNA synthetase/tRNA (RS/tRNA) pairs have been developed to introduce a ncAA at the desired site, delivering a wide variety of functionalities that can be installed into selected proteins. Cytoplasmic expression of RS/tRNA pairs can cause a problem with background ncAA incorporation into host proteins. The application of orthogonally translating organelles (OTOs), inspired by the concept of phase separation, provides a solution for this issue in mammalian cells, allowing site-specific and protein-selective ncAA incorporation. So far, only Methanosarcina mazei (Mm) pyrrolysyl-tRNA synthetase (PylRS) has been used within OTOs, limiting the method's potential. Here, we explored the implementation of four other widely used orthogonal RS/tRNA pairs with OTOs, which, to our surprise, were unsuccessful in generating mRNA-selective GCE. Next, we tested several experimental solutions and developed a new chimeric phenylalanyl-RS/tRNA pair that enables ncAA incorporation in OTOs in a site-specific and protein-selective manner. Our work reveals unaccounted design constraints in the spatial engineering of enzyme functions using designer organelles and presents a strategy to overcome those in vivo. We then discuss current limitations and future directions of in-cell engineering in general and protein engineering using GCE specifically.

Hypothalamic neurons fully or partially expressing the dopaminergic phenotype: development, distribution, functioning and functional significance. A review.

The hypothalamus is a key link in neuroendocrine regulations, which are provided by neuropeptides and dopamine. Until the late 1980 s, it was believed that, along with peptidergic neurons, hypothalamus contained dopaminergic neurons. Over time, it has been shown that besides dopaminergic neurons expressing the dopamine transporter and dopamine-synthesizing enzymes - tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) - the hypothalamus contains neurons expressing only TH, only AADC, both enzymes or only dopamine transporter. The end secretory product of TH neurons is L-3,4-dihydroxyphenylalanine, while that of AADC neurons and bienzymatic neurons lacking the dopamine transporter is dopamine. During ontogenesis, especially in the perinatal period, monoenzymatic neurons predominate in the hypothalamic neuroendocrine centers. It is assumed that L-3,4-dihydroxyphenylalanine and dopamine are released into the neuropil, cerebral ventricles, and blood vessels, participating in the regulation of target cell differentiation in the perinatal period and the functioning of target cells in adulthood.

Integration of microbiome, metabolomics and transcriptome for in-depth understanding of berberine attenuates AOM/DSS-induced colitis-associated colorectal cancer.

A type of colorectal cancer (CRC)，Colitis-associated colorectal cancer (CAC)， is closely associated with chronic inflammation and gut microbiota dysbiosis. Berberine (BBR) has a long history in the treatment of intestinal diseases, which has been reported to inhibit colitis and CRC. However, the mechanism of its action is still unclear. Here, this study aimed to explore the potential protective effects of BBR on azoxymethane (AOM)/dextransulfate sodium (DSS)-induced colitis and tumor mice, and to elucidate its potential molecular mechanisms by microbiota, genes and metabolic alterations. The results showed that BBR inhibited the gut inflammation and improved the function of mucosal barrier to ameliorate AOM/DSS-induced colitis. And BBR treatment significantly reduced intestinal tumor development and ki-67 expression of intestinal tissue along with promoted apoptosis. Through microbiota analysis based on the 16 S rRNA gene, we found that BBR treatment improved intestinal microbiota imbalance in AOM/DSS-induced colitis and tumor mice, which were characterized by an increase of beneficial bacteria, for instance Akkermanisa, Lactobacillus, Bacteroides uniformis and Bacteroides acidifaciens. In addition, transcriptome analysis showed that BBR regulated colonic epithelial signaling pathway in CAC mice particularly by tryptophan metabolism and Wnt signaling pathway. Notably, BBR treatment resulted in the enrichment of amino acids metabolism and microbiota-derived SCFA metabolites. In summary, our research findings suggest that the gut microbiota-amino acid metabolism-Wnt signaling pathway axis plays critical role in maintaining intestinal homeostasis, which may provide new insights into the inhibitory effects of BBR on colitis and colon cancer.

l-Arginine supplementation for pregnant and lactating sows may improve the performance of piglets: A systematic review.

The objective was to conduct a systematic review to clarify the effects of l-arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin-like growth factor 1 (IGF-1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l-arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF-1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets.

Nutrient Sensing of mTORC1 signaling in cancer and aging.

The mechanistic target of rapamycin complex 1 (mTORC1) is indispensable for preserving cellular and organismal homeostasis by balancing the anabolic and catabolic processes in response to various environmental cues, such as nutrients, growth factors, energy status, oxygen levels, and stress. Dysregulation of mTORC1 signaling is associated with the progression of many types of human disorders including cancer, age-related diseases, neurodegenerative disorders, and metabolic diseases. The way mTORC1 senses various upstream signals and converts them into specific downstream responses remains a crucial question with significant impacts for our perception of the related physiological and pathological process. In this review, we discuss the recent molecular and functional insights into the nutrient sensing of the mTORC1 signaling pathway, along with the emerging role of deregulating nutrient-mTORC1 signaling in cancer and age-related disorders.

Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.