Search Results (172)

Background High-sensitivity C-reactive protein (hs-CRP) is a protein that indicates inflammation and the risk of cardiovascular diseases. The intake of dietary amino acids can influence immune and inflammatory reactions. However, studies on the relationship between dietary amino acids and hs-CRP, especially in children, remain scarce. Methods This cross-sectional study analyzed data from the Nutrition and China Children and Lactating Women Nutrition and Health Survey (2016–2019), focusing on 3514 children (724 with elevated hs-CRP ≥ 3 mg/L and 2790 with normal levels). Dietary information was gathered via a food frequency questionnaire, and hs-CRP levels were obtained from blood samples. Boruta algorithm and propensity scores were used to select and match dietary factors and sample sizes. Machine learning (ML) algorithms and logistic regression models assessed the link between amino acid intake and elevated hs-CRP risk, adjusting for age, sex, BMI, and lifestyle factors. Results The odds ratios (ORs) for elevated hs-CRP were significant for several amino acids, including Ile, Leu, Lys, Ser, Cys, Tyr, His, Pro, SAA, and AAA, with values ranging from 1.10 to 2.07. The LightGBM algorithm was the most effective in predicting elevated hs-CRP risk, achieving an AUC of 0.927. Tyrosine, methionine, cysteine, and proline were identified as important features by SHAP analysis and logistic regression. The intake of Ser, Cys, Tyr, and Pro showed a linear increase in the risk of elevated hs-CRP, especially in individuals with low protein intake and normal weight (p < 0.1). Conclusions Intake of amino acids like Ser, Cys, Tyr, and Pro significantly impacts hs-CRP levels in children, indicating that regulating these could help prevent inflammation-related diseases. This study supports future dietary and health management strategies. This is first large-scale ML study linking amino acids to pediatric inflammation in China. The main limitations are the cross-section design and the use of self-reported dietary data. Full article

The integration of chirality into nanomaterials holds significant potential for improving molecular recognition and biomedical technologies. In this work, we fabricated novel chiral horned gold nanostructures (HNS) by controlling the concentration of chiral ligands L-/D-cysteine (Cys). The unique three-dimensional morphology with horns-rotational arrangement enables synergistic optimization of chiral optical responses and surface-enhanced Raman scattering (SERS) performance. The proposed chiral HNSs can be used to recognize amino acid enantiomers, in which homochiral amino acid has distinct affinities to the chiral HNSs of homogeneous handedness. The 4-mercaptobenzoic acid (4-MPBA)-modified D-HNS demonstrates significantly enhanced targeting affinity for D-amino acids in the Escherichia coli (E. coli) cell wall, enabling successful amplification of SERS signals and advancing bacterial detection methodologies. By demonstrating the rotation-selective interaction between chiral HNSs and circularly polarized light (CPL), D-HNS exhibits excellent photothermal conversion efficiency under right-handed circularly polarized light (RCP) irradiation. This enables the synergistic combination of targeted physical disruption and photothermal sterilization, which leads to efficient eradication of E. coli. The D-HNS hydrogel composite system further expands the practical application of photothermal sterilization. Altogether, chiral HNSs have achieved SERS detection of bacteria and efficient polarization photothermal sterilization, which helps further develop applications based on chiral nanomaterials. Full article

This study aimed to assess the nutritional value of whole corn germ (WCG) in the diet of chickens. Amino acid digestibility, fatty acid digestibility, and metabolizable energy were evaluated. A metabolism assay was conducted using the precise feeding method on roosters. A completely randomized design was used, with two treatments and ten replications per rooster in each experimental unit. The treatments were as follows: WCG1, precise feeding with WCG; and WCG2, fasting birds to determine metabolic and endogenous losses in energy and fat. The variables analyzed were coefficients for amino acids in corn germ meal and fatty acid digestibility. The results showed that the standardized digestibility coefficients for amino acids in corn germ meal were (in g/kg) as follows: Lys, 920; Thr, 780; Met + Cys, 800; Arg, 910; His, 890; Ile, 950; Leu, 970; Phe + Tyr, 870; Val, 980; Gly + Ser, 740; Ala, 960; Asp, 870; and Glu, 930. The average fatty acid digestibility and AMEn were 850 g/kg and 4934 kcal/kg, respectively. Corn germ meal, which showed high digestibility of nutrients and energy, is considered an interesting ingredient for diets requiring high energy concentration. Full article

Beckmannia syzigachne is one of the most competitive weeds in winter wheat fields in China. In this study, 120 suspected resistant populations of Beckmannia syzigachne were collected from the Anhui, Hubei, Jiangsu, and Shandong Provinces from 2017 to 2019. In total, 110 populations exhibited different levels of resistance to clodinafop-propargyl, 114 populations expressed different levels of resistance to mesosulfuron-methyl, and 105 populations were resistant to both herbicides at different levels. The resistant weeds were mainly distributed in Anhui and Jiangsu Provinces. The detection results of acetyl coA carboxylase (ACCase) and acetolactate synthase (ALS) genes in the resistant populations indicated that ACCase gene mutations occurred in 97 out of 110 populations resistant to clodinafop-propargyl and ALS gene mutations occurred in 25 out of 114 populations resistant to mesosulfuron-methyl. There were several mutation types, including Ile-1781-Leu, Trp-2027-Cys, Ile-2041-Asn, Ile-2041-Val, Asp-2078-Gly, and Gly-2096-Ala in the ACCase sequence and Pro-197-Ser, Pro-197-Thr, Pro-197-His, Pro-197-Leu, Asp-376-Glu, and Trp-574-Leu in the ALS sequence. Among these mutation types, Pro-197-His, Asp-376-Glu, and Trp-574-Leu in the ALS sequence were the first identified in Beckmannia syzigachne. Full article

Botanical dietary supplements are widely used, but issues of authenticity, consistency, safety, and efficacy that complicate their poorly understood mechanism of action have prompted questions and concerns in the popular and scientific literature. Black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa, Nutt., Ranunculaceae) is a multicomponent botanical therapeutic used as a popular remedy for menopause and dysmenorrhea and explored as a treatment in breast and prostate cancer. However, its use and safety are controversial. A. racemosa tissues contain the bioactive serotonin analog N-methylserotonin, which is thought to contribute to the serotonergic activities of black cohosh–containing preparations. A. racemosa has several TDC-like genes hypothesized to encode tryptophan decarboxylases (TDCs) converting L-tryptophan to tryptamine, a direct serotonin precursor in plants. Expression of black cohosh TDC1, TDC2, and TDC3 in Saccharomyces cerevisiae resulted in the production of tryptamine. TDC1 and TDC3 had approximately fourfold higher activity than TDC2, which was attributable to a variable Cys/Ser active site residue identified by site-directed mutagenesis. Co-expression in yeast of the high-activity black cohosh TDCs with the next enzyme in serotonin biosynthesis, tryptamine 5-hydroxylase (T5H), from rice (Oryza sativa) resulted in the production of serotonin, whereas co-expression with low-activity TDCs did not, suggesting that TDC activity is a rate-limiting step in serotonin biosynthesis. Two T5H-like sequences were identified in A. racemose, but their co-expression with the high-activity TDCs in yeast did not result in serotonin production. TDC expression was detected in several black cohosh tissues, and phytochemical analysis using LC-MS revealed several new tryptamines, including tryptamine and serotonin, along with N-methylserotonin and, interestingly, N-N-dimethyl-5-hydroxytryptamine (bufotenine), which may contribute to hepatotoxicity. Incubation of A. racemosa leaves with tryptamine and N-methyltryptamine resulted in increased concentrations of serotonin and N-methylserotonin, respectively, suggesting that methylation of tryptamine precedes hydroxylation in the biosynthesis of N-methylserotonin. This work indicates a significantly greater variety of serotonin derivatives in A. racemosa than previously reported. Moreover, the activities of the TDCs underscore their key role in the production of serotonergic compounds in A. racemosa. Finally, it is proposed that tryptamine is first methylated and then hydroxylated to form the black cohosh signature compound N-methylserotonin. Full article

Host defense antimicrobial peptides (AMPs) are promising lead molecules with which to develop antibiotics against drug-resistant bacterial pathogens. Thanatin, an inducible antimicrobial peptide involved in the host defense of Podisus maculiventris insects, is gaining considerable attention in the generation of novel classes of antibiotics. Thanatin or thanatin-based analog peptides are extremely potent in killing bacterial pathogens in the Enterobacteriaceae family, including drug-resistant strains of Escherichia coli and Klebsiella pneumoniae. A single disulfide bond that covalently links two anti-parallel β-strands in thanatin could be pivotal to its selective antibacterial activity and mode of action. However, potential correlations of the disulfide covalent bond with structure, activity and target binding in thanatin peptides are currently unclear to. Here, we examined a 16-residue designed thanatin peptide, namely disulfide-bonded VF16QK, and its Cys to Ser substituted variant, VF16QK^Ser, to delineate their structure–activity relationships. Bacterial growth inhibitory activity was only detected for the disulfide-bonded VF16QK peptide. Mechanistically, both peptides vastly differ in their bacterial cell permeabilizations, atomic-resolution structures, interactions with the LPS-outer membrane and target periplasmic protein LptA_m binding. In particular, analysis of the 3-D structures of the two peptides revealed an altered folded conformation for the VF16QK^Ser peptide that was correlated with diminished LPS-outer membrane permeabilization and target interactions. Analysis of docked complexes of LPS–thanatin peptides indicated potential structural requirements and conformational adaptation for antimicrobial activity. Collectively, these observations contrast with those for the disulfide-bonded β-hairpin antimicrobial protegrin and tachyplesin peptides, where disulfide bonds are dispensable for activity. We surmise that the atomistic structures and associated molecular interactions presented in this work can be utilized to design novel thanatin-based antibiotics. Full article

Pathogenic variants in the USH2A gene are the primary cause of both non-syndromic autosomal recessive inherited retinitis pigmentosa (RP) and the syndromic form, characterized by retinal degeneration and sensorineural hearing loss. This study presents a comparative assessment of the genetic variant spectrum in the USH2A gene among Russian patients in two clinical groups. A retrospective analysis was conducted on massive parallel panel sequencing data from 2415 blood samples of unrelated patients suspected of having hereditary retinal diseases. The copy number of USH2A exons was determined using the quantitative MLPA method with the MRC-Holland SALSA MLPA kit. Biallelic pathogenic and likely pathogenic variants in the USH2A gene were identified in 69 patients (8.7%). In the group of patients with isolated hereditary RP (55 patients), the most frequent pathogenic variants were p.(Glu4445_Ser4449delinsAspLeu) (20.9%), p.(Trp3955*) (15.5%), and p.(Cys934Trp) (5.5%). In patients with the syndromic form (14 patients), the most frequent variants were p.(Trp3955*) (35.7%) and c.8682-9A>G (17.9%). It was found that patients with isolated vision impairment rarely had two “null” variants (17.8%), whereas this was common among patients with both hearing and vision impairment (71.4%) (p ≤ 0.05), explaining the severity of the disease and the earlier onset of clinical symptoms in the syndromic form of RP. Ten previously undescribed loss-of-function variants were identified. The estimated prevalence of USH2A-associated retinal dystrophy in Russia was 1.9 per 100,000 individuals. The obtained data on the differences in the spectra of genetic variants in the USH2A gene in the two studied groups highlight the importance of establishing genotype–phenotype correlations and predicting disease severity, aiming at potential early cochlear implantation and selection of target therapy. Full article

Pancreatic lipase is an enzyme crucial for breaking down fats through hydrolysis, and inhibiting it is important for managing obesity. This study evaluated the lipase inhibitory profile of the leaf (SALE) and vine (SAVE) of Secamone afzelii, explored the modes of inhibition, identified the primary compounds responsible for this effect, and examined their molecular interactions with lipase using in vitro and in silico techniques. SALE (IC50: 0.41 ± 0.02 mg/mL) exhibited higher lipase inhibitory activity compared to SAVE (IC50: 0.95 ± 0.05 mg/mL), although it was significantly lower than orlistat (IC50: 0.07 ± 0.00 mg/mL) across all concentrations. S. afzelii extracts inhibited lipase activity through an uncompetitive mode of inhibition. Gas chromatography-mas spectroscopy identified 54 and 47 compounds in SALE and SAVE, respectively, with 9,12-octadecadienoic acid (Z, Z)-, n-hexadecanoic acid and 4S,6R-dimethyl-7R-hydroxynonan-3-one identified as the most abundant compounds in both extracts. The binding energy of the top five ligands from S. afzelii ranged from −7.7 to −6.6 kcal/mol, outperforming that of orlistat (−4.4 kcal/mol). The ligands and orlistat had similar binding poses stabilised by hydrogen and π interactions with CYS299, SER301, CYS304, ASN425 and VAL426. These compounds were predicted to possess promising pharmacokinetic, lipophilic and hydrophilic properties. These results offer insights into the traditional use of S. afzelii for treating obesity and valuable information on potential drug candidates that can be optimised for combating this disease. Full article

Two model experiments were conducted to investigate the different protein and amino acid supply of laying hens fed split feeding (SF) diets. In Experiment 1, one conventional (C) and one SF dietary treatment were established, and the diets were implemented for 12 weeks. The concentrations of crude protein, SID Lys, Met, Met + Cys Arg, Val, Thr, Leu, Ile, and Trp of the SF morning diet were the same as in the C diet. The crude protein content of the SF afternoon diet was lower (92%), while the SID values of Lys, Met, Met + Cys were identical compared to the C diet (100%). The SF treatment resulted in a reduced protein/N intake, better feed conversion ratio, higher eggshell thickness and apparent ileal digestibility of Asp, Leu, Lys, Gly, and Ser, and lower concentration of N forms (total, fecal, NH₄⁺, uric acid, urinary) in the excreta compared to the C treatment. In Experiment 2, a control and a low protein (−2% crude protein but the same SID values of Lys, Met, Met + Cys, Thr, Val) SF treatment were compared for 6 weeks. The low protein SF treatment led to a decreased protein/N intake, higher laying rate, lower egg weight, higher ileal digestibility of Ala, Asp, Leu, and Ile, and similar N emission compared to the control SF treatment. Full article

Background/Objectives: 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a form of oxidative DNA damage caused by oxidative stress (OS), which is considered a major factor in male infertility. The cellular defense system against 8-OHdG involves base excision repair (BER) with the enzyme 8-Oxoguanine DNA glycosylase 1 (OGG1). However, studies on the single-nucleotide polymorphism (SNP) OGG1 Ser326Cys have demonstrated that the Cys326Cys genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 Ser326Cys polymorphism and its effect on DNA oxidation were evaluated in 118 infertile men. Methods: Polymorphic screening was performed using TaqMan allelic discrimination assays, and oxidative DNA damage was evaluated through the quantification of 8-OHdG and total antioxidant capacity (TAC); in addition, electrical bioimpedance spectroscopy (EBiS) measurements were used as a reference for different electrical properties associated with 8-OHdG concentrations. Results: The detected Cys (G) allele frequency (0.4) was higher compared to the allele frequency reported in the “Allele Frequency Aggregator” (ALFA) and “Haplotype Map” (HapMap) projects for American populations (0.21–0.29), suggesting that the Cys (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the Cys326Cys (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in Cys326Cys (GG) genotype carriers compared to the other genotypes. Moreover, the EBiS magnitude exhibited potential for the detection of different oxidative damage in DNA samples between genotypes. Conclusions: The Cys326Cys (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility. Full article

It is not known why the number of proteinogenic amino acids is limited to 20. Since Miller’s experiment, many studies have shown that amino acids could have been generated under prebiotic conditions. However, the amino acid compositions obtained from simulated experiments and exogenous origins are different from those of life. We hypothesized that some simple precursor compounds generated by high-energy reactions were selectively combined by organic reactions to afford a limited number of amino acids. To this direction, we propose two scenarios. One is the reaction of HCN with each side-chain precursor (the aminomalononitrile scenario), and the other is alkylation of the “complex glycine precursor”, which is the main product of proton irradiation of the primordial atmosphere (the new polyglycine scenario). Here, selective formation of the 20 amino acids is described focusing on the latter scenario. The structural features of proteinogenic amino acids can be described systematically. The scenario consists of three stages: a high-energy reaction stage (Gly, Ala, Asn, and Asp were established); an alkylation stage (Gln, Glu, Ser, Thr, Val, Ile, Leu, and Pro were generated in considerable amounts); and a peptide formation stage (Phe, Tyr, Trp, His, Lys, Arg, Cys, and Met were selected due to their structural advantages). This scenario is a part of the evolution of Garakuta World, in which many prebiotic materials are contained. Full article

Peptides are receiving significant attention in pharmaceutical sciences due to their applications as anti-inflammatory drugs; however, many aspects of their interactions and mechanisms at the molecular level are not well-known. This work explores the molecular structure of two peptides—(i) cysteine (Cys)–asparagine (Asn)–serine (Ser) (CNS) as a molecule in the gas phase and solvated in water in zwitterion form, and (ii) the crystal structure of the dipeptide serine–asparagine (SN), a reliable peptide indication whose experimental cell parameters are well known. A search was performed by means of atomistic calculations based on density functional theory (DFT). These calculations matched the experimental crystal structure of SN, validating the CNS results and useful for assignments of our experimental spectroscopic IR bands. Our calculations also explore the intercalation of CNS into the interlayer space of montmorillonite (MNT). Our quantum mechanical calculations show that the conformations of these peptides change significantly during intercalation into the confined interlayer space of MNT. This intercalation is energetically favorable, indicating that this process can be a useful preparation for therapeutic anti-inflammatory applications and showing high stability and controlled release processes. Full article

The aim of this study was to develop new materials with adsorbent properties that can be used for the adsorption recovery of Au(III) from aqueous solutions. To achieve this result, it is necessary to obtain inexpensive adsorbent materials in a granular form. Concomitantly, these materials must have a high adsorption capacity and selectivity. Other desired properties of these materials include a higher physical resistance, insolubility in water, and materials that can be regenerated or reused. Among the methods applied for the separation, purification, and preconcentration of platinum-group metal ions, adsorption is recognised as one of the most promising methods because of its simplicity, high efficiency, and wide availability. The studies were carried out using three supports: cellulose (CE), chitosan (Chi), and diatomea earth (Diat). These supports were functionalised by impregnation with extractants, using the ultrasound method. The extractants are environmentally friendly and relatively cheap amino acids, which contain in their structure pendant groups with nitrogen and sulphur heteroatoms (aspartic acid—Asp, l-glutamic acid—Glu, valine—Val, DL-cysteine—Cys, or serine—Ser). After preliminary testing from 75 synthesised materials, CE-Cys was chosen for the further recovery of Au(III) ions from aqueous solutions. To highlight the morphology and the functionalisation of the material, we physicochemically characterised the obtained material. Therefore, the analysis of the specific surface and porosity showed that the CE-Cys material has a specific surface of 4.6 m²/g, with a porosity of about 3 nm. The FT-IR analysis showed the presence, at a wavelength of 3340 cm⁻¹, of the specific NH bond vibration for cysteine. At the same time, pHpZc was determined to be 2.8. The kinetic, thermodynamic, and equilibrium studies showed that the pseudo-second-order kinetic model best describes the adsorption process of Au(III) ions on the CE-Cys material. A maximum adsorption capacity of 12.18 mg per gram of the adsorbent material was achieved. It was established that the CE-Cys material can be reused five times with a good recovery degree. Full article

Parkinson’s disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disorder inducing movement alterations as a result of the loss of dopaminergic (DAergic) neurons of the pars compacta in the substantia nigra and protein aggregates of alpha synuclein (α-Syn). Although its etiopathology agent has not yet been clearly established, environmental and genetic factors have been suggested as the major contributors to the disease. Mutations in the glucosidase beta acid 1 (GBA1) gene, which encodes the lysosomal glucosylceramidase (GCase) enzyme, are one of the major genetic risks for PD. We found that the GBA1 K198E fibroblasts but not WT fibroblasts showed reduced catalytic activity of heterozygous mutant GCase by −70% but its expression levels increased by 3.68-fold; increased the acidification of autophagy vacuoles (e.g., autophagosomes, lysosomes, and autolysosomes) by +1600%; augmented the expression of autophagosome protein Beclin-1 (+133%) and LC3-II (+750%), and lysosomal–autophagosome fusion protein LAMP-2 (+107%); increased the accumulation of lysosomes (+400%); decreased the mitochondrial membrane potential (∆Ψm) by −19% but the expression of Parkin protein remained unperturbed; increased the oxidized DJ-1Cys106-SOH by +900%, as evidence of oxidative stress; increased phosphorylated LRRK2 at Ser935 (+1050%) along with phosphorylated α-synuclein (α-Syn) at pathological residue Ser129 (+1200%); increased the executer apoptotic protein caspase 3 (cleaved caspase 3) by +733%. Although exposure of WT fibroblasts to environmental neutoxin rotenone (ROT, 1 μM) exacerbated the autophagy–lysosomal system, oxidative stress, and apoptosis markers, ROT moderately increased those markers in GBA1 K198E fibroblasts. We concluded that the K198E mutation endogenously primes skin fibroblasts toward autophagy dysfunction, OS, and apoptosis. Our findings suggest that the GBA1 K198E fibroblasts are biochemically and molecularly equivalent to the response of WT GBA1 fibroblasts exposed to ROT. Full article

Ascorbate peroxidases (APXs) are key components of the ascorbate–glytathione cycle, which plays an important role in removing excess reactive oxygen species (ROS) in plants. Herein, MaAPX1 was verified as being involved in the ripening and senescence of banana fruit, exhibiting responsiveness to the accumulation of ROS and the oxidation of proteins. Site-directed mutation was applied to explore the mechanism of MaAPX1 activity changes. We found that the 32-site cysteine (Cys, C) served as a potential S-nitrosylation site. The mutant MaAPX1^C32S activity was decreased significantly when Cys32 was mutated to serine (Ser, S). Intriguingly, the neighboring conserved 36-site methionine (Met, M), which is adjacent to Cys32, displayed an enzyme activity that was approximately five times higher than that of the wild-type MaAPX1 when mutated to lysine (Lys, K). Utilizing LC-MS/MS spectroscopy coupled with stopped-flow analysis showed that the enhanced MaAPX1^M36K activity might be due to the increased S-nitrosylation level of Cys32 and the promotion of intermediate (compound I, the first intermediate product of the reaction of APX with H₂O₂) production. Molecular docking simulations showed that the S-N bond between Cys32 and Lys36 in MaAPX1^M36K might have a function in protecting the thiol of Cys32 from oxidation. MaAPX1^M36K, a promising mutant, possesses immense potential for improving the antioxidant capabilities of APX in the realm of bioengineering technology research. Full article