Amino Acid Research Articles

A Pilot Study of Enterade (VS001), an Oral Amino Acid Formulation, in Malnourished Bangladeshi Children with Environmental Enteric Dysfunction

A Pilot Study of Enterade (VS001), an Oral Amino Acid Formulation, in Malnourished Bangladeshi Children with Environmental Enteric Dysfunction

Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini.

Dipeptide production mediated by dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11 plays a crucial role in growth of Porphyromonas gingivalis, a periodontopathic asaccharolytic bacterium. Given the particular P1-position specificity of DPPs, it has been speculated that DPP5 or DPP7 might be responsible for degrading refractory P1 amino acids, i.e., neutral (Thr, His, Gly, Ser, Gln) and hydrophilic (Asn) residues. The present results identified DPP7 as an entity that processes these residues, thus ensuring complete production of nutritional dipeptides in the bacterium. Activity enhancement by the P1' residue was observed in DPP7, as well as DPP4 and DPP5. Toward the refractory P1 residues, DPP7 uniquely hydrolyzed HX|LD-MCA (X=His, Gln, or Asn) and their hydrolysis was most significantly suppressed in dpp7 gene-disrupted cells. Additionally, hydrophobic P2 residue significantly enhanced DPP7 activity toward these substrates. The findings propose a comprehensive 20 P1×20 P2 amino acid matrix showing the coordination of four DPPs to achieve complete dipeptide production along with subsidiary peptidases. The present finding of a broad substrate specificity that DPP7 accounts for releasing 48 % (192/400) of N-terminal dipeptides could implicate its potential role in linking periodontopathic disease to related systemic disorders.

The efficacy of dietary supplements on health status and performance of football players: a systematic review.

This study aimed to review the efficacy of commonly used supplements on the health status and performance of football players. We searched several databases forrelevant publications published in English upto June 2024 using keywords such as nutritional supplementation, performance, football, and football players. The available literature indicated that l-arginine supplements may improve cardiovascular function, ventilation, the serum level of lactate, and maximal oxygen consumption (VO2 Max) of football players. Branched-chain amino acids (BCAAs) may improve multiple-choice reaction time. Creatine supplements improve jumping, sprinting, change of direction speed, and reduce fatigue. Among thevitamins, vitamin D improves the serum level of injury-related hormones such as cortisol and testosterone. Bvitamins reduce the level of blood lactate in the recovery periods. Vitamin E and vitamin C may improve performance by decreasing oxidative stress and increasing the antioxidant capacity and oxygen delivery to exercising skeletal muscles. Iron supplementation improves endurance capacity. Further studies are warranted to confirm the effects of the supplements on football players, to identify the appropriate dosage ofthe supplements and also to determine their mechanism ofaction.

Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients

Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabolites in PE patients and identify potential predictive biomarkers for suspected PE patients (pregnant women who had already shown PE-related symptoms in the middle to late stages of pregnancy, but were not yet confirmatively diagnosed as PE.), a large-scale serum metabolomic analysis was conducted in this study with a prospective cohort of 328 suspected PE patients in the middle or late pregnancy stages, as well as a retrospective cohort of 30 healthy pregnant women and 30 PE patients. Using liquid chromatography mass spectrometry (LC − MS), serum metabolomic profiling revealed that the development of PE was closely associated with disturbed amino acid metabolism. Moreover, a panel of seven predictive biomarkers including 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, gamma-glutamyl-leucine, 2-hydroxyvaleric acid, LysoPC(16:1(9Z)/0:0), PC(DiMe(13,5)/MonoMe(13,5)), ADP-D-glycero-beta-D-manno-heptose and phenylalanyl-tryptophan were identified for PE development by performing multiple statistical analysis and LASSO regression analysis. The combination of these biomarkers showed promise in the prediction of PE development for suspected PE patients, with an AUC of 0.753 and 0.885 for the discovery and validation cohorts, respectively. These findings highlight the potential of large-scale prospective metabolomic studies combined with machine learning algorithms in identifying key biomarkers for predicting PE development, while retrospective metabolomics studies provide insights into the pathogenesis of PE.

Microbial diversity, functional attributes, and nutritional proficiency of yogurts produced in Bangladesh

Bangladeshi yogurt is a creamy, tangy dairy product with culinary significance in Bangladesh, often consumed alone or as a complement to spicy dishes. This study investigates the microbial diversity and nutritional composition in 38 samples, spanning commercial and locally produced varieties from eight districts. Through 16S rRNA amplicon sequencing, 650 Operational Taxonomic Units (OTUs) were identified: sour yogurt contained 493 OTUs, and sweet yogurt 441 OTUs. Firmicutes were predominant across both yogurt types, with unique appearances of Gracilibacteria, Gemmatimonadetes, and Spirochaetes in sour yogurt, while Euryarchaeota and Lentisphaerae were found only in sweet yogurt. Streptococcus and Lactobacillus emerged as the most abundant genera, with local sour samples presenting lower Firmicutes levels (84.98%) compared to commercial types (> 99.27%). Among the samples, those from Cox's Bazar exhibited the greatest bacterial diversity. Nutritional assessments revealed that branded yogurts were denser in nutrients, especially solids-not-fat (SNF), total solids, and essential minerals like iron and zinc. In contrast, local yogurts contained higher fat and lower sodium, appealing to consumers favoring richer textures with less salt. Increased acidity in local varieties also matched preferences for tangier flavors. Physicochemical analysis identified a negative association between Lactobacillus levels and pH, while higher fat content reduced overall bacterial diversity except for Lactobacillus, which further decreased mineral bioavailability. Carbohydrate metabolism was dominant in both types, with increased amino acid metabolism (11.72%) and xenobiotics biodegradation (3.94%) in sour yogurt. This study underscores the health-promoting properties of Bangladeshi yogurt, highlighting its unique regional microbiological and biochemical characteristics.

The role of amino acids and protein administration in preventing cardiac surgery-associated acute kidney injury.

Acute kidney injury (AKI) persists as one of the most common complications after cardiac surgery. Beyond being burdened by high morbidity and mortality rates, effective therapeutic options are still lacking. To date, the management of cardiac surgery-associated AKI (CSA-AKI) mainly focuses on preventive strategies, e.g. the implementation of standardized care bundles. Interestingly, recent experimental studies have suggested a potential nephroprotective role for both amino acids (AA) and proteins. As such, these compounds show multiple beneficial renal effects, spanning enhancement of renal blood flow, improved oxygenation, and recruitment of renal functional reserve. Moreover, clinical studies have investigated the therapeutic potential of single AA, AA combinations, and proteins. A recent large multicenter randomized controlled trial showed reduced AKI incidence in cardiac surgery patients receiving intravenous AA supplementation. However, these interventions have not yet demonstrated beneficial effects on major clinical outcomes, such as survival. Given the well-established AA safety profile and the underlying biological rationale supporting their use, this review summarizes the existing literature on the effects of various formulations and combinations of perioperative AA and protein on renal outcomes when administered in cardiac surgery patients.

Association of asparagine in saliva with a lower risk of early childhood caries in undernourished children: a cross-sectional study.

The aim was to investigate the salivary amino acid profile in children with protein-energy undernutrition (PEU) and its association with caries experience in the presence of other risk factors. The study had a cross-sectional design and was carried out with 122 children (12-71months old), classified according to their level ofundernutrition (mild-GI, n = 22; moderate-GII, n = 53) or healthy controls (GC, n = 47). The children were categorized based on the presence of caries into caries-experienced groups (ceos > 0, 22 CG, 12 GI and 18 GII) and caries-free groups (ceos = 0, 25 CG, 10 GI and 36 GII). Total unstimulated and stimulated saliva were collected to determine amino acids and Streptococcus mutans, respectively. Eighteen amino acids were associated with PEU. Undernutrition and caries experience influenced the presence of thefollowing amino acids: L-anserine, asparagine, ethanolamine, gamma-aminobutyric acid,and norleucine. Asparagine was a significant predictor of a lower probability of caries experience in a logistic regression model. Salivary amino acids are associated with undernutrition in children, and the presence of asparagine in saliva relates to a lower caries risk.

Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc.

Intervertebral disc degeneration (IVD) is a leading cause of low back pain, a prevalent musculoskeletal condition. IVD degeneration is characterized by the degradation of nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates (EP). Growth Differentiation Factor 6 (GDF6), part of the bone morphogenetic protein family, has demonstrated potential in maintaining disc integrity. However, its precise role in cellular protein synthesis during IVD degeneration remains unclear. This study employed Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) to investigate the effects of GDF6 on protein synthesis in NP, AF, and EP cells isolated from degenerated human IVDs. Cells were cultured in SILAC media with and without GDF6 treatment. The proteomic profiles were analyzed via mass spectrometry, comparing newly synthesized "heavy" proteins with pre-existing "light" proteins. GDF6 treatment altered protein synthesis in degenerated IVD cells. In NP cells, GDF6 reduced the synthesis of matrisome proteins, including collagens and proteoglycans, while promoting proteins associated with ECM stability, such as LOX, PCOLCE and HAPLN1/3. AF cells demonstrated an upregulation of ECM-stabilizing proteins like POSTN and FMOD. EP cells showed minimal changes, but GDF6 enhanced the synthesis of collagen type II, suggesting improved ECM integrity. Secretome analysis revealed that GDF6 modulated extracellular signalling by promoting ECM-stabilizing proteins and reducing inflammatory markers. GDF6 exerts compartment-specific effects on protein synthesis in degenerated IVDs, promoting ECM stability, reducing fibrosis, and potentially preserving hydration. These findings support the potential of GDF6 as a therapeutic agent in treating IVD degeneration, particularly in NP-targeted therapies. Future studies should optimize GDF6 dosing and delivery to maximize its regenerative potential.

Impaired cognitive function and decreased monoamine neurotransmitters in the DNAJC12 gene knockout mouse model

BackgroundHyperphenylalaninemia, a prevalent amino acid metabolism disorder, often results in cognitive impairment. Recent studies have identified a rare variant of this disorder caused by mutations in the DNAJC12 gene. The specific mechanisms by which DNAJC12 mutations lead to hyperphenylalaninemia and the lack of an animal model for study remain significant gaps in understanding.PurposeThis study aims to elucidate the role of DNAJC12 in intellectual disability and explore the mechanisms by which DNAJC12 deficiency leads to hyperphenylalaninemia through developing a DNAJC12 gene knockout mouse model.MethodsWe thoroughly examined the clinical features and genetic mutations evident in two patients with biallelic mutations in the DNAJC12 gene. Based on the patient’s mutation locations, we determined the target site for the knockout utilizing CRISPR/Cas9 technology. To assess the impact of these mutations on DNAJC12 expression, we used quantitative real-time PCR and Western blotting techniques to measure mRNA and protein levels, respectively. The Morris water maze test was administered to evaluate the cognitive functions of the mice. Additionally, we utilized High-Performance Liquid Chromatography (HPLC) to measure serum aromatic amino acids and brain monoamines, facilitating an investigation into the metabolism of phenylalanine and tyrosine.ResultsWe reported two patients with mutations in the DNAJC12 gene. Case 1 carried the mutations c.158-1G > A and c.262 C > T in the DNAJC12 gene. He presented with nocturnal eye closure, crying, and arching back in reverse tension before treatment, suggesting a neurotransmitter metabolism disorder. Case 2 carried the mutations c.473 C > G, and c.102 deletion in the DNAJC12 gene. He showed elevated blood phenylalanine levels, although further clinical details were not available. Based on the patients’ mutation locations, exons 2–4 of the DNAJC12 gene were targeted and eliminated. In our animal model experiments, DNAJC12 gene knockout mice exhibited a complete absence of DNAJC12 expression at both mRNA and protein levels. These knockout mice showed significant deficits in learning and memory performance as assessed by the Morris water maze test. Quantitative real-time PCR analysis indicated no significant differences in the levels of aromatic amino hydroxylases between knockout and wild-type mice. However, Western blot analysis revealed a substantial reduction in phenylalanine hydroxylase (PAH) protein levels in the liver of knockout mice, while tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression remained unchanged. HPLC analysis demonstrated increased serum Phe concentrations and decreased levels of brain neurotransmitters in the knockout group.ConclusionsWe report two patients with four novel DNAJC12 mutations (c.158-1G > A, c.262 C > T, c.473 C > G, c.102delT), expanding the mutation spectrum. Based on the patients’ mutation location, we established the first DNAJC12 gene knockout mouse model. The knockout mice exhibit hyperphenylalaninemia, impaired cognitive function, and decreased monoamine neurotransmitters. DNAJC12 deficiency may contribute to the clinical phenotype via the PAH pathway, potentially at the post-transcriptional level.

Soil organic matter composition affects ecosystem multifunctionality by mediating the composition of microbial communities in long-term restored meadows

BackgroundSoil organic matter composition and microbial communities are key factors affecting ecosystem multifunctionality (EMF) during ecosystem restoration. However, there is little information on their interacting mechanisms in degraded and restored meadows. To fill this knowledge gap, plant, root and soil samples from alpine swamp meadows, alpine Kobresia meadows, severely degraded alpine meadows, short-term restored meadows (< 5 years) and long-term restored meadows (6–14 years) were collected. We leveraged high-throughput sequencing, liquid chromatography and mass spectrometry to characterize soil microbial communities and soil organic matter composition, measured microbial carbon metabolism and determined EMF.ResultsIt emerged that the similarity of soil microorganisms in meadows decreased with increasing heterogeneity of soil properties. Dispersal limitation and ecological drift led to the homogenization of the bacterial community. Based on co-occurrence network analysis, an increase in microbial network complexity promoted EMF. Root total phosphorus and soil organic matter components were the key predictors of EMF, while organic acids and phenolic acids increased the stability of the microbial network in long-term restored meadows. Carbon metabolism did not increase in restored meadows, but the niche breadth of soil microorganisms and the utilization efficiency of small molecular carbon sources such as amino acids did increase.ConclusionsThese findings emphasize the importance of soil organic matter composition in ecological restoration and that the composition should be considered in management strategies aimed at enhancing EMF.

The optimization of calcareous soil cation exchange capacity via the feather hydrolysate and N-P fertilizers integration

Adding organic amendments to agricultural systems as sustainable practices is one of the most important stages toward creating a more sustainable and environmentally friendly food system. By increasing soil fertility and nutritional content, organic fertilizers increase plant productivity. Cation Exchange Capacity (CEC) is a vital indicator of soil fertility and plant nutrient availability, which is considered one of the most significant chemical parameters that affect agricultural soil quality. The main goals of the present study were to generate protein lysate from discarded feathers (enriched in different amino acids) through solid-state fermentation using Box-Behnken design (BBD). Then, assess the efficacy of hydrolyzed feather product (as an organic amendment), time, and N-P fertilizers on soil-CEC planted with maize in calcareous soil utilizing an optimization strategy that employed the central composite design and the response surface methodology (RSM). The results revealed that the protein concentration in the customized conditions was 1173.53 µg ml−1. With a predicted CEC of 31.416 cmolc kg−1, the ideal circumstances for the three variables under investigation of feather hydrolysate, time, and chemical fertilizer were 20.147 ml kg−1 soil, 27 days, and 42.3% of the recommended dose, respectively. Using keratin hydrolysate (20 ml kg−1 soil) as a soil amendment significantly improved the growth parameters of maize. The leaf surface area (SA, m2 gm−1) was increased by 695% and 37% compared to the control (without any addition) and N-P fertilizer treatments (100% of the recommended dose), respectively. Keratin hydrolysate as a sustainable production of value-added organic fertilizer applied to calcareous soil shows a synergistic effect on soil-CEC and plant growth parameters.

CuII(l-Phe)2-H]+ Complex: A Versatile Selector for Wide Enantiomeric Excess Determination and Chiral Recognition in Complicated Matrices by Post-column Infusion LC-Energy-resolved MS/MS.

Enantiomeric measurement of complicated matrices always challenges LC-MS/MS. Efforts were made here to pursue a fit-for-purpose chiral selector (CS) for LC-MS/MS and to clarify the enantioselective mechanisms. After assaying diverse candidates for 22 pairs of enantiomers, differentiation was successful for 15 pairs when employing [CuII(l-Phe)2-H]+ as the CS. With d- vs l-proline (Pro) as representatives, diastereomeric complex ions such as [CuII(d-Pro)(l-Phe)2-H]+ and [CuII(l-Pro)(l-Phe)2-H]+ were formed and their featured fragment ions such as [CuII(d/l-Pro)(l-Phe)-H]+ and [CuII(l-Phe)2-H]+ exhibited different abundance ratios (R). R was linearly correlated with enantiomeric excess (ee %), and Rmax, termed as the R value at optimal collision energy, enabled chiral recognition. Crystallization was successful for both [CuII(d-Pro)(l-Phe)-2H] and [CuII(l-Phe)2-2H] complexes, and X-ray spectroscopy revealed that the distorted square planar configuration by tetrahedrally coordinating Cu2+ to two nitrogen atoms and two oxygen atoms from (Phe)2 or (d-Pro)(l-Phe) led to enantioselectivity. The diastereomeric complex was constructed by an octahedron core consisting of six spatially orthometric coordination bonds around nuclear CuII. ΔG differences for the generations of [CuII(d/l-Pro)(l-Phe)-H]+ and [CuII(l-Phe)2-H]+ contributed to enantioselective MS/MS behaviors. Because of mirror images between [CuII(d-Pro)(l-Phe)2-H]+ and [CuII(l-Pro)(d-Phe)2-H]+, l-Pro solely completed ee % determination. By correlating R to ee %, simultaneous ee % determination for nine pairs of amino acid (AA) enantiomers was reached in cell medium extracts. Through correlating Rmax to ΔG, chiral recognition, even configurational determination, was achieved for AA enantiomers and pyranocoumarin enantiomers in the complicated matrices. Together, [CuII(l-Phe)2-H]+ is an eligible CS to facilitate post-column infusion LC-energy-resolved MS/MS allowing wide ee % determination and chiral recognition in complicated samples.

Comparative genetic analysis of pathogenic and attenuated strains of Junín virus.

Junín virus (JUNV) is a mammarenavirus that causes Argentine hemorrhagic fever (AHF). Mammarenaviruses are RNA viruses with an ambisense, bi-segmented genome containing four genes encoding the glycoproteins (GPC), the nucleoprotein (NP), the RNA polymerase (L) and the matrix protein (Z). Several JUNV strains with different pathogenicity have already been fully sequenced. We performed a comprehensive and comparative analysis of their genetic differences and phylogeny, focusing on the synonymous codon usage patterns of the JUNV proteins. We found a nucleotide identity of > 95% between strains, with significant differences between all genes for GC% and Z and L genes for GC3%. Analysis of relative synonymous codon usage showed that codons AGA and AGG of the amino acid arginine were overrepresented, while CGC, CGA and CGG of arginine, GCG of alanine, ACG of threonine, CCG of proline and TCG of serine were underrepresented in the GPC, NP and L genes. A weak codon usage bias was observed, with GPC having a significantly higher effective number of codons. Moreover, selection could explain at least 83% of the observed bias. Analysis of the codon adaptation index revealed a better adaptation for B cells and kidney and a lower one for endothelial cells. We also observed a possible reassortment event between the MC2 and Romero strains. This work provides a new perspective on the genetic diversity of JUNV strains, which may contribute to the development of new approaches for future research into the evolutionary model, origin and host adaptation of JUNV causing AHF.

Nutrient Composition and Antioxidant Properties of Fish Protein Hydrolysate from Bullet Tuna (Auxis rochei)

Background: Bullet Tuna (Auxis Rochei) is commonly found in Indonesian waters and its distribution in the world includes warm waters (tropical and subtropical). The utilization of this fish is still minimal because people prefer to consume it as a daily side dish. The high protein content in Bullet Tuna has the potential to be processed into fish protein hydrolysate (FPH) which has a higher economic value for applying in the food and pharmaceutical fields. Methods: This study aims to obtain FPH from Bullet Tuna using the bromelain enzyme. The method used to produce FPH was hydrolyzing muscle tissue with variations of the bromelain at 2, 3, 4, 5 and 6% (w/v) at 55ºC for 6 hours. Result: Characteristics of the best FPH obtained by the addition of bromelain 6% (w/v) were observed as protein content of 77.80%, nitrogen content of 12.45%, water content of 7.32%, fat content of 0.97%, ash content of 11.88% and degree of hydrolysis of 60.46%. It had 15 types of amino acids and an antioxidant activity value of 94.05 ppm. Results suggested that the FPH of Bullet Tuna produced showed a promising additive for food and industrial applications.

ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism

BackgroundProstate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is the early identification of aggressive cases for targeted treatment, while avoiding unnecessary interventions in slow-progressing cases. Therefore, there is a critical need for genetic biomarkers that can distinguish between aggressive and non-aggressive PrCa cases. Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. However, the function of ANO7 in the prostate remains unknown.MethodsWe performed RNA-sequencing (RNA-seq) on RWPE1 cells engineered to express ANO7 protein, alongside the analysis of a single-cell RNA-sequencing (scRNA-seq) dataset and RNA-seq from prostate tissues. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to identify key pathways. Additionally, we assessed oxidative phosphorylation (OXPHOS), glycolysis, and targeted metabolomics. Image analysis of mitochondrial morphology and lipidomics were also performed to provide further insight into the functional role of ANO7 in prostate cells.ResultsANO7 expression resulted in the downregulation of metabolic pathways, particularly genes associated with the MYC pathway and oxidative phosphorylation (OXPHOS) in both prostate tissue and ANO7-expressing cells. Measurements of OXPHOS and glycolysis in the ANO7-expressing cells revealed a metabolic shift towards glycolysis. Targeted metabolomics showed reduced levels of the amino acid aspartate, indicating disrupted mitochondrial function in the ANO7-expressing cells. Image analysis demonstrated altered mitochondrial morphology in these cells. Additionally, ANO7 downregulated genes involved in fatty acid metabolism and induced changes in lipid composition of the cells, characterized by longer acyl chain lengths and increased unsaturation, suggesting a role for ANO7 in regulating lipid metabolism in the prostate.ConclusionsThis study provides new insights into the function of ANO7 in prostate cells, highlighting its involvement in metabolic pathways, particularly OXPHOS and lipid metabolism. The findings suggest that ANO7 may act as a key regulator of cellular lipid metabolism and mitochondrial function in the prostate, shedding light on a previously unknown aspect of ANO7’s biology.

Severe deviation in protein fold prediction by advanced AI: a case study

Artificial intelligence (AI) and deep learning are making groundbreaking strides in protein structure prediction. AlphaFold is remarkable in this arena for its outstanding accuracy in modelling proteins fold based solely on their amino acid sequences. In spite of these remarkable advances, experimental structure determination remains critical. Here we report severe deviations between the experimental structure of a two-domain protein and its equivalent AI-prediction. These observations are particularly relevant to the relative orientation of the domains within the global protein scaffold. We observe positional divergence in equivalent residues beyond 30 Å, and an overall RMSD of 7.7 Å. Significant deviation between experimental structures and AI-predicted models echoes the presence of unusual conformations, insufficient training data and high complexity in protein folding that can ultimately lead to current limitations in protein structure prediction.

Deep Learning Combined with Quantitative Structure‒Activity Relationship Accelerates De Novo Design of Antifungal Peptides.

Novel antifungal drugs that evade resistance are urgently needed for Candida infections. Antifungal peptides (AFPs) are potential candidates due to their specific mechanism of action, which makes them less prone to developing drug resistance. An AFP de novo design method, Deep Learning-Quantitative Structure‒Activity Relationship Empirical Screening (DL-QSARES), is developed by integrating deep learning and quantitative structure‒activity relationship empirical screening. After generating candidate AFPs (c_AFPs) through the recombination of dominant amino acids and dipeptide compositions, natural language processing models are utilized and quantitative structure‒activity relationship (QSAR) approaches based on physicochemical properties to screen for promising c_AFPs. Forty-nine promising c_AFPs are screened, and their minimum inhibitory concentrations (MICs) against C. albicans are determined to be 3.9-125 µgmL-1, of which four leading c_AFPs (AFP-8, -10, -11, and -13) has MICs of <10 µgmL-1 against the four tested pathogenic fungi, and AFP-13 has excellent therapeutic efficacy in the animal model.

Thin Films of Poly(ionic liquids) Containing l-Alanine and l-Serine Amino Acids for Immobilization of Laccase

Thin Films of Poly(ionic liquids) Containing <scp>l</scp>-Alanine and <scp>l</scp>-Serine Amino Acids for Immobilization of <i>Laccase</i>

A Dual-Functional Fluorescent Chemosensor Derived from Naphthalene Dithiouryl for Cu2+: Applications in Water Analysis, Logic Gates, Swab Tests, and Pesticide Monitoring.

A chemosensor (CNS) built on a naphthalene fluorophore was developed, featuring a disulfide-bridged dimer structure. The probe CNS was completely characterized by the usual spectral analysis methods like 1H NMR, 13C NMR, and HR-MS. The CNS probe selectively detects Cu2+ ions and subsequently recognizes the amino acid tryptophan in a semi-aqueous medium of DMF:H2O solution. The detection of Cu2+ ions occur via three distinct mechanisms: suppression of the photoinduced electron-transfer process (PET), arrested rotation of diuryl groups leading to conformational change, and a blue-shifted fluorescence enhancement through intramolecular charge-transfer (ICT). With a 1:1 complexation ratio and a detection limit of 2.14 x 10-4 M, the CNS probe has been successfully applied in various practical scenarios, including real water sample analysis, glyphosate detection, smartphone-based color detection, and Cu2+ ion testing using a cotton-swab method.

Blocking the shikimate pathway amplifies the impact of carvacrol on biofilm formation in Candida albicans.

Candida albicans typically thrives in a commensal relationship with humans but is also an opportunistic fungal pathogen. As an opportunistic pathogen, C. albicans relies heavily on its ability to assimilate nutrients, for which it must compete with the host and other microorganisms. Amino acid biosynthesis, sensing, and uptake play pivotal roles in C. albicans growth and pathogenicity. C. albicans biosynthesizes aromatic amino acids and co-enzyme Q de novo through the shikimate pathway, including the Aro1, Aro2, and Aro7 enzymes, but also has amino acid transporters for uptake from the environment. Thus, antifungal approaches targeting aromatic amino acid biosynthesis must simultaneously inhibit amino acid biosynthesis and uptake. Herein, we investigate the plant-based antifungal, carvacrol, in conjunction with aromatic amino acid biosynthetic mutants, as a potential anti-candidal strategy. Growth of the WT, ARO2, and ARO7 strains were inhibited by 150 µg/mL carvacrol, whereas the ARO1 mutant was slightly more sensitive (with MIC 125 µg/mL). All repressed mutants exposed to carvacrol are partially rescued in the presence of para-aminobenzoic acid (PABA) (CoQ precursor), indicating that blocking the shikimate pathway impacts both aromatic amino acid and CoQ biosynthesis. Moreover, carvacrol at sublethal concentrations significantly inhibits ARO1 adhesion and hyphal formation, along with pre-attached and pre-formed hyphae, ultimately impacting biofilm metabolic activity and biomass accumulation and significantly reducing biofilm growth. In summary, carvacrol increases the sensitivity of C. albicans to ARO1 repression, with attenuated adhesion, hyphal formation, mycelial growth and biofilm formation, likely by blocking aromatic amino acid uptake.IMPORTANCEThe opportunistic pathogen Candida albicans remains the leading cause of candidemia and invasive candidiasis (IC), causing significant morbidity and mortality in immunocompromised patients. Our current arsenal of effective antifungal drugs is limited in number, mechanistic diversity, and efficacy, are cytotoxic and associated with antifungal resistance, necessitating the development of novel antifungals and combination therapies. Here, we show how simultaneously blocking the shikimate pathway, through ARO1 repression, and disrupting aromatic amino acid uptake by carvacrol prevent C. albicans biofilm formation. Thus, inhibitors of the Aro1 enzyme in combination with carvacrol are expected to shut down C. albicans biofilm formation and virulence.