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Histidine (His) is a semi-essential amino acid and a unique key neurotransmitter involved in numerous physiological processes. An excessive or deficient amount of His in the body can lead to various related diseases. However, since the chemical structures of L-His and its metabolites (such as histamine (Ha), imidazole-4-acetate (ImA), etc. ) are very similar, simple and efficient selective detection of L-His and its related metabolites is of great importance but remains a great challenge. Herein, we successfully designed and synthesized a DMSO-assisted iridium(III) complex (Ir1-DMSO), which can be applied as a "turn-on" photoluminescence (PL) probe for the selective detection and quantification of L-His/Ha. More importantly, Ir1-DMSO exhibited good sensitivity, high selectivity, and anti-interference capability for L-His/Ha/His-containing proteins, which is advantageous due to its simple fabrication and low technical demands. This was attributed to the reaction of Ir1-DMSO with imidazole and amino groups of L-His/Ha. Furthermore, we show the utility of Ir1-DMSO as a PL imaging agent in cultures of E. coli and S. aureus . Considering its diversity of composition and structural flexibility, it can be extended to other solvents and Ir-ligand complexes for various analyses based on specific molecular recognition sensing platforms.

L-cysteine, an indispensable amino acid present in natural proteins, plays pivotal roles in various biological processes. Consequently, precise and selective monitoring of its concentrations is imperative. Herein, we propose a Surface-enhanced Raman Scattering (SERS) sensor for detecting L-cysteine based on the anti-aggregation of 4-mercaptobenzoic acid (4-MBA) and histidine (His) functionalized silver nanoparticles (Ag NPs). The presence of Hg 2+ ions can induce the aggregation of Ag NPs@His@4-MBA due to the unique nanostructures of Ag NPs@His@4-MBA, resulting in a robust SERS intensity of 4-MBA. However, in the presence of L-cysteine, the stronger affinity between L-cysteine and Hg 2+ reduces the concentration of free Hg 2+ , causing the dispersion of the aggregated functionalized Ag NPs and the reduction of the SERS signal intensity of 4-MBA. The developed SERS platform demonstrates excellent performance with a low detection limit of 5 nM (S/N = 3) and linear detection capabilities within the range of 0.01-100 μM for L-cysteine. Additionally, the method was successfully employed for the determination of L-cysteine in spiked serum samples, yielding recoveries ranging from 95.0 % to 108.1 % with relative standard deviations of less than 3.3 %. This study not only presents a novel approach for fabricating highly sensitive and specific SERS biosensors for biomolecule detection but also offers a significant strategy for the development and construction of SERS substrates using anti-aggregation design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Amino acids are not only the building blocks of proteins but also lead to the development of novel nanomaterials with unique properties. Herein, we proposed a simple strategy to produce gold nanoparticles (Au NPs) with peroxidase-like (POD-like) activities by using a series of amino acids as reducing agents, named Au NPs@M (M represents different amino acids). The Au NPs@His was identified as the nanozyme with the most potent catalytic performance, which was used in combination with smartphones to achieve rapid detection of hydrogen peroxide with a detection limit of 0.966 μM. It also enables rapid detection of glucose with a detection limit of 2.904 μM, highlighting the significant contribution of Au NPs@His in expediting the detection of critical biomolecules. This work not only provides a convenient and highly efficient method to identify glucose but also shows the potential of histidine as a reducing agent in constructing Au nanomaterials exerting enzyme-like catalysis., (© 2024 Wiley-VCH GmbH.)

This research aims to assess the effect of amino acids as lipid antioxidants in reducing the formation of volatile aldehydes in frying oil. Methionine, histidine, and glycine at concentrations of 2.5, 5, and 10 mM were added to high oleic sunflower oil (HOSO) to investigate their effects on the distribution and formation of saturated, monounsaturated, and polyunsaturated volatile aldehydes. The results showed that the proportion of saturated volatile aldehydes was greater than that of unsaturated ones; Methionine exhibited the best inhibitory effect, after 12 h of frying, 10 mM methionine reduced the content of saturated volatile aldehydes by 24.21 %, monounsaturated by 52.4 %, and polyunsaturated by 54.73 % compared to the control. Methionine's sulfur-containing side chain was also proven to have strong antioxidant activity. Combined with the results of this study, this can also provide insights for using amino acids as lipid antioxidants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Low fluorescence under visible light excitation and catalytic activity limit many applications of graphene quantum dots in optical detection, biosensing, catalysis and biomedical. The paper reports design and synthesis of histidine, serine and folic acid-functionalized and boron and iron-doped graphene quantum dot (Fe/B-GQD-HSF). The Fe/B-GQD-HSF shows excellent fluorescence behavior and peroxidase-like activity. Excitation of 330 nm ultraviolet light produces the strongest blue fluorescence and excitation of 480 nm visible light produces the strongest yellow fluorescence. The specific activity reaches 92.67 U g -1 , which is higher than that of other graphene quantum dots. The Fe/B-GQD-HSF can catalyze oxidation of 3,3',5,5'-tetramethylbenzidine with H 2 O 2 to form blue compound. Based on this, it was used for colorimetric and fluorescence detection of H 2 O 2 . The absorbance at 652 nm linearly increases with the increase of H 2 O 2 concentration between 0.5 and 100 μM with detection limit of 0.43 μM. The fluorescence signal linearly decreases with the increase of H 2 O 2 concentration between 0.05 and 100 μM with detection limit of 0.035 μM. The analytical method has been satisfactorily applied in detection of H 2 O 2 in food. The study also paves one way for design and synthesis of functional graphene quantum dots with ideal fluorescence behavior and catalytic activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study introduces a novel approach for the sensitive and accurate detection of small molecule metabolites, employing metal-phenolic network (MPN) functionalized AuNPs as both adsorbent and matrix to enhance laser desorption/ionization mass spectrometry (LDI-MS) performance. The MPN comprising tannic acid (TA) and transition metal ions (Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , or Zn 2+ ) was coated on the surface of AuNPs, forming metal-TA network-coated AuNPs (M-TA@AuNPs). The M-TA@AuNPs provided a tunable surface for specific interactions with analytes, displaying distinct enrichment efficacies for different amino acids, especially for Cu-TA@AuNPs exhibiting the highest affinity for histidine (His). Under the optimized condition, the proposed method enabled ultrasensitive detection of His, with good linearity (R 2  = 0.9627) in the low-concentration range (50 nM-1 μM) and a limit of detection (LOD) as low as 0.9 nM. Furthermore, the method was successfully applied to detect His from human urine samples, showcasing its practical applications in clinical diagnostics, particularly in the realm of amino acid-based targeted metabolomics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Histidine phosphorylation (pHis) plays a key role in signal transduction in prokaryotes and regulates tumour initiation and progression in mammals. However, the pHis substrates and their functions are rarely known due to the lack of effective analytical strategies., Results: Herein, we provide a strategy for unbiased enrichment and assignment of the pHis peptides. First, the entire procedure was designed under alkaline conditions to maintain the stability of the N-P bond of pHis and high-pH reverse-phase chromatography was used to efficiently separate the pHis peptides. Second, exploiting the coelution benefits of diethyl labelling, the ratios of light- and heavy-labelled peptides were accurately quantified, and the sites of phosphorylated histidine were assigned. Finally, Cu-IDA bead enrichment and data-independent acquisition mass spectrometry analysis were used to improve the coverage of the histidine phosphoproteome. With this novel strategy, 768 and 1125 potential pHis peptides were identified from lysates of E. coli and HeLa cells, respectively. And these values represent the highest coverage of the histidine phosphoproteome for both cell types., Significance: These data strongly support the presumption that pHis modifications are widely present in bacteria. The study provides an efficient strategy and can lead to a better understanding of pHis-modified substrates and their biological functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gold nanoparticles (Au NPs) have been widely utilized in developing DNAzyme-functionalized nanosensors, most of which were engineered by attaching the thiolated DNAzymes to Au NPs via Au-S bonding. However, the Au NP-DNAzyme nanosensors always suffer from signal distortion when applied in complex environment with abundant thiols, which poses challenge for practical applications. Here, we focus on addressing the root cause of the issue and propose to decorate the Au NPs with a thin layer of platinum, thus facilitating the conjugation of DNAzymes through Pt-S bonding, a thiol-resistant cross-linking. The Pt-S bond stabilized DNAzyme nanosensor effectively minimized false positive signals when detecting l-histidine in infant formulas, as compared to the Au-S stabilized counterpart. This innovative strategy holds promise for high-fidelity biosensing, improving the practical applicability of Au NP-based DNAzyme nanosensor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quantifying reactive aldehyde biomarkers, such as malondialdehyde, acrolein, and crotonaldehyde, is the most preferred approach to determine oxidative stress. However, reported analytical methods lack specificity for accurately quantifying these aldehydes as certain methodologies may produce false positive results due to harsh experimental conditions. Thus, in this research work, a novel HILIC-MS/MS method with endogenous histidine derivatization is developed, which proves to have higher specificity and reproducibility in quantifying these aldehydes from the biological matrix. To overcome the reactivity of aldehyde, endogenous histidine is used for its derivatization. The generated adduct is orthogonally characterized by NMR and LC-HRMS. The method employed a hydrophilic HILIC column and multiple reaction monitoring (MRM) to accurately quantify these reactive aldehydes. The developed method is an unequivocal solution for quantifying stress in in vivo and in vitro studies.

The analysis of dietary supplements is far less regulated than pharmaceuticals, leading to potential quality issues. Considering their positive effect, many athletes consume supplements containing L-histidine and β-alanine. A new microfluidic method for the determination of L-histidine and β-alanine in dietary supplement formulations has been developed. For the first time, capacitively coupled contactless conductivity detection was employed for the microchip electrophoresis of amino acids in real samples. A linear relationship between detector response and concentration was observed in the range of 10-100 µmol L -1 for L-histidine (R 2  = 0.9968) and β-alanine (R 2  = 0.9954), while achieved limits of detection (3 × S/N ratio) were 4.2 µmol L -1 and 5.2 µmol L -1 , respectively. The accuracy of the method was confirmed using recovery experiments as well as CE-UV-VIS and HPLC-UV-VIS techniques. The developed method allows unambiguous identification of amino acids in native form without chemical derivatization and with the possibility of simultaneous analysis of amino acids with metal cations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

In this study, Cu 2+ modulated silver nanoclusters were constructed for the turn-on, label-free detection of L-histidine. Six Ag NCs protected by oligonucleotides (DNA-Ag NCs) were tested in a series of experiments. Finally, A-DAN-Ag NCs were chosen as the best candidate due to their excellent fluorescent properties. The fluorescence of A-DAN-Ag NCs was quenched using Cu 2+ through energy or electron transfer. However, quenched fluorescence could be restored dramatically in the presence of L-histidine due to Cu 2+ liberation from A-DAN-Ag NCs and because of the chelation between the imidazole group of L-histidine and Cu 2+ . The proposed sensor exhibited high selectivity towards L-histidine over other amino acids, with a limit of detection (LOD) of 0.096 μM ranging from 0 to 8 μM. The proposed sensor succeeded in detecting L-histidine in diluted human urine. Therefore, the sensor has promising practical applications in biological systems.

An assay that integrates histidine-rich peptides (HisRPs) with high-affinity aptamers was developed enabling the specific and sensitive determination of the target lysozyme. The enzyme-like activity of HisRP is inhibited by its interaction with a target recognized by an aptamer. In the presence of the target, lysozyme molecules progressively assemble on the surface of HisRP in a concentration-dependent manner, resulting in the gradual suppression of enzyme-like activity. This inhibition of HisRP's enzyme-like activity can be visually observed through color changes in the reaction product or quantified using UV-visible absorption spectroscopy. Under optimal conditions, the proposed colorimetric assay for lysozyme had a detection limit as low as 1 nM and exhibited excellent selectivity against other nonspecific interferents. Furthermore, subsequent research validated the practical applicability of the developed colorimetric approach to saliva samples, indicating that the assay holds significant potential for the detection of lysozymes in samples derived from humans., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Histidine plays an essential role in most biological systems. Changes in the homeostasis of histidine and histidine-rich proteins are connected to several diseases. Herein, we report a water-soluble Cu(II) coordination polymer, labeled CuCP, for the fluorimetric detection of histidine and histidine-rich proteins and peptides. Single-crystal structure determination of CuCP revealed a two-dimensional wavy network structure in which a carboxylate group connects the individual Cu(II) dimer unit in a syn-anti conformation. The weakly luminescent and water-soluble CuCP shows turn-on blue emission in the presence of histidine and histidine-rich peptides and proteins. The polymer can also stain histidine-rich proteins via gel electrophoresis. The limits of quantifications for histidine, glycine-histidine, serine-histidine, human serum albumin (HSA), bovine serum albumin, pepsin, trypsin, and lysozyme were found to be 300, 160, 600, 300, 600, 800, 120, and 290 nM, respectively. Utilizing the fluorescence turn-on property of CuCP, we measured HSA quantitatively in the urine samples. We also validated the present urinary HSA measurement assay with existing analytical techniques. Job's plot, 1 H NMR, high-resolution mass spectrometry (HRMS), electron paramagnetic resonance (EPR), fluorescence, and UV-vis studies confirmed the ligand displacement from CuCP in the presence of histidine.

Milk is widely recognized as an important food source with health benefits. Different consumer groups have different requirements for the content and proportion of milk fat; therefore, it is necessary to investigate the differential metabolites and their regulatory mechanisms in milk with high and low milk fat percentages (MFP). In this study, untargeted metabolomics was performed on milk samples from 13 cows with high milk fat percentage (HF) and 13 cows with low milk fat percentage (LF) using ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS). Forty-eight potential differentially labeled compounds were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) combined with the weighted gene co-expression network analysis (WGCNA) method. Amino acid metabolism was the key metabolic pathway with significant enrichment of L-histidine, 5-oxoproline, L-aspartic acid, and L-glutamic acid. The negative correlation with MFP differentiated the HF and LF groups. To further determine the potential regulatory role of these amino acids on milk fat metabolism, the expression levels of marker genes in the milk fat synthesis pathway were explored. It was noticed that L-histidine reduced milk fat concentration primarily by inhibiting the triglycerides (TAG) synthesis pathway. L-aspartic acid and L-glutamic acid inhibited milk fat synthesis through the fatty acid de novo and TAG synthesis pathways. This study provides new insights into the mechanism underlying milk fat synthesis and milk quality improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In Japan, the promotion of effective use of many wild deer as food resource has been conducted. However, they are not necessarily utilized effectively. Thus, we focused physiologically functional compounds to find characteristics of Sika deer meats (commercially available) obtained from different regions such as Hokkaido, Wakayama, Tokushima, and Miyazaki prefectures in Japan, making it a valuable resource for future studies and applications. The amount of carnosine, anserine, and balenine in muscle of deer from Wakayama prefecture was significantly lower than that in muscle of deer from other prefectures. The differences of amount of imidazole dipeptides in different prefectures seems to be caused by feed, rearing environment, and breed. The amount of carnitine in deer meat from Hokkaido was significantly lower than that in muscle of deer from other prefectures, while the amount of acetyl-carnitine in deer meat from Miyazaki prefectures was significantly higher than that from other prefectures. The amounts of glutamine, ornithine, and 3-methylhistidine in muscles of deer from Wakayama prefectures were significantly higher than those in muscle of deer from other prefectures. These results might be caused by differences in feeding habits, habitat, the muscle types, and subspecies of deer obtained from four regions in Japan., (© 2024 Japanese Society of Animal Science.)

Aggregation of α-synuclein (α-syn) into amyloid is the pathological hallmark of several neurodegenerative disorders, including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. It is widely accepted that α-syn aggregation is associated with neurodegeneration, although the mechanisms are not yet fully understood. Therefore, the inhibition of α-syn aggregation is a potential therapeutic approach against these diseases. This study used the photocatalyst for α-syn photo-oxygenation, which selectively adds oxygen atoms to fibrils. Our findings demonstrate that photo-oxygenation using this photocatalyst successfully inhibits α-syn aggregation, particularly by reducing its seeding ability. Notably, we also discovered that photo-oxygenation of the histidine at the 50th residue in α-syn aggregates is responsible for the inhibitory effect. These findings indicate that photo-oxygenation of the histidine residue in α-syn is a potential therapeutic strategy for synucleinopathies., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Herbivorous animals that regularly consume tannin-rich food are known to secrete certain tannin-binding salivary proteins (TBSPs), especially proline-rich proteins and histidine-rich proteins, as an effective measure to counteract the antinutritive effects of dietary tannins. Due to their high binding capacity, TBSPs complex with tannins in the oral cavity, and thereby protect dietary proteins and digestive enzymes. Although the natural diet of great apes (Hominidae) is biased toward ripe fruits, analyses of food plants revealed that their natural diet contains considerable amounts of tannins, which is raising the question of possible counter-measures to cope with dietary tannins. In our study, we investigated the salivary amino acid profiles of zoo-housed Pan paniscus, Pan troglodytes, Gorilla gorilla, and Pongo abelii, and compared their results with corresponding data from Homo sapiens. Individual saliva samples of 42 apes and 17 humans were collected and quantitated by amino acid analysis, using cation-exchange chromatography with postcolumn derivatization, following acid hydrolysis. We found species-specific differences in the salivary amino acid profiles with average total salivary protein concentration ranging from 308.8 mg/dL in Po. abelii to 1165.6 mg/dL in G. gorilla. Total salivary protein was consistently higher in ape than in human saliva samples (174 mg/dL). All apes had on average also higher relative proline levels than humans did. Histidine levels had the highest concentration in the samples from Po. abelii followed by P. paniscus. In all ape species, the high salivary concentrations of proline and histidine are considered to be indicative of high concentrations of TBSPs in hominids. Given that the species differences in salivary composition obtained in this study correspond with overall patterns of secondary compound content in the diet of wild populations, we assume that salivary composition is resilient to acute and long-lasting changes in diet composition in general and tannin content in particular., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Forest environment has many health benefits, and negative air ions (NAI) is one of the major forest environmental factors. Many studies have explored the effect of forest environment on cardiac autonomic nervous function, while forest NAI in the among function and the underlying mechanism still remain unclear. To explore the associations and molecular linkages between short-term exposure to forest NAI and heart rate variability (HRV), a repeated-measure panel study was conducted among 31 healthy adults. Participants were randomly selected to stay in a forest park for 3 days and 2 nights. Individual exposures including NAI were monitored simultaneously and HRV indices were measured repeatedly at the follow-up period. Urine samples were collected for non-targeted metabolomics analysis. Mixed-effect models were adopted to evaluate associations among NAI, HRV indices and metabolites. The median of NAI concentration was 68.11 (138.20) cm -3 during the study period. Short-term exposure to forest NAI was associated with the ameliorative HRV indices, especially the excitatory parasympathetic nerve. For instance, per interquartile range increase of 5-min moving average of NAI was associated with 9.99 % (95%CI: 8.95 %, 11.03 %) increase of power in high frequency. Eight metabolites were associated with NAI exposure. The down-regulated tyrosine metabolism was firstly observed, followed by other amino acid metabolic alterations. The NAI-related metabolic changes reflect the reduction of inflammation and oxidative stress. HRV indices were associated with 25 metabolites, mainly including arginine, proline and histidine metabolism. Short-term exposure to forest NAI is beneficial to HRV, especially to the parasympathetic nerve activity, by successively disturbing different metabolic pathways which mainly reflect the increased anti-inflammation and the reduced inflammation. The results will provide epidemiological evidences for developing forest therapy and improving cardiac autonomic nervous function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Endogenous benzoic acid causes adverse effects on individual health, but the potential mechanisms often remain elusive. The positive rate of benzoic acid in seventy-two goat milk samples in triplicate was 93.6 %, verifying the presence of endogenous benzoic acid. In this study, we investigated the differences in protein expression and metabolites among goat milk with different final concentrations of benzoic acid via combined proteomics and metabolomics (LOQ 3.25 to 56.63 μg L -1 ) analysis based on UHPLC-Q-Orbitrap HRMS. Integrated analysis showed that benzoic acid reduced the content of l-histidine (from 1.27 to 0.49 mg/L) and 1-methylhistidine (from 1.40 to 0.68 mg/L), due to the increase of benzoic acid (0-30 mg/L) concentration significantly reduced the level and activity of N-methyltransferase. Protein-metabolite interactions suggested that benzoic acid enhanced glutamate-cysteine ligase and glutathione S-transferase expression and affected l-glutamate (from 1.22 to 0.49 mg/L) and glutathione contents, eventually leading to the formation of off-flavors and oxidation of goat milk. Meanwhile, the level of l-phenylalanine (from 4.17 to 1.94 mg/L) and l-tyrosine (from 1.05 to 0.26 mg/L) progressively decreased with the increase of benzoic acid concentration, which had a deleterious effect on the nutritional value and flavor formation of goat milk. These findings clarified the mechanism by which low-dose benzoic acid negatively affects the nutritional quality and flavor formation of goat milk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A direct fluorimetric method, employing μicro-analytical paper-based devices (μ-PADs) for the selective determination of histidine (HIS) is described. The suggested method exploits the fluorescence emission of histidine after its rapid reaction with o-phthalaldehyde (OPA) at a basic medium (pH = 10) on the surface of a paper device with the application of a UV lamp at 354 nm. The devices are inexpensive and are composed of chromatographic paper and wax barriers. The analytical protocol is easily applicable with minimal technical expertise and without the need of expensive experimental apparatus. The user has to add a test sample, illuminate the device with a UV lamp, and read the fluorescence of the sensing area using a simple imaging device such as a cell-phone camera. The method is free from common interferences likely to affect the measurement of histidine and is selective among all other amino acids. This analytical procedure was optimized and validated, paying special attention to its intended application. The detection limits are as low as 1.8 μM with very satisfactory precision ranging from 6.4% (intra-day) to 8.9% (inter-day). Random urine samples from adult volunteers (n = 5) were successfully analyzed and HIS content ranged between 260 and 1114 μmol L -1 with percentage recoveries in the range of 78.2 and 124.6%., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This work firstly developed a near-infrared fluorescence capillary imprinted sensor with high selectivity and sensitivity for the chiral recognition of l-histidine. The near-infrared fluorescence imprinted polymer prepared by sol-gel method using CdTe quantum dots as the near-infrared fluorescence source was self-sucked into activated capillary to form the fluorescence imprinted capillary. The fluorescence imprinted capillary sensor had higher fluorescence response efficiency. With the superior stability, reproducibility and reusability, the fluorescence capillary imprinted sensor displayed higher selectivity toward l-histidine. Under the optimal conditions, the fluorescence intensity (λex = 370 nm, λem = 695 nm) of the fluorescence capillary imprinted sensor was enhanced in proportion to l-histidine concentration ranged from 0.1 pM to 1.8 pM with a limit of detection of 0.08 pM. Spiking experiment showed that the fluorescence capillary imprinted sensor was successfully used for determination of l-histidine in human urine and serum with the recoveries of 99.6-102.7%. The near-infrared fluorescence capillary imprinted sensor possessed significantly potential for high sensitive detection of l-histidine, which realized trace-level analysis for micro-volume sample and provided promising utility for green chemical., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Fecal metabolomic profiles differ between pediatric inflammatory bowel disease (IBD) patients and controls and may provide new insights in the pathophysiology of IBD. The role of amino acids, however, is not fully elucidated. We aimed to assess fecal amino acid profiles in pediatric IBD., Methods: In this case-control study, treatment-naïve, newly diagnosed pediatric IBD patients and a non-IBD control group, matched based on sex and age, were included in 2 tertiary centres. Fecal amino acid profiles were assessed using a targeted high-performance liquid chromatography technique. A random forest classifier method was used to develop a prediction model differentiating IBD from controls and predicting IBD phenotype. The association between IBD localization and amino acid concentrations was tested with ordinal regression models., Results: We included 78 newly diagnosed IBD patients (40 Crohn's disease [CD], 38 ulcerative colitis [UC]) and 105 controls. Patients with IBD could be differentiated from controls with an accuracy of 82% (sensitivity 63%, specificity 97%). Twenty-nine out of the 42 measured unique amino acids were included in the prediction model. Increased levels of tryptophan, taurine, alanine, ornithine, valine, histidine, and leucine were the most differentiating features. Children with CD and UC could be differentiated from the controls with an accuracy of 80% and 90%, respectively. Inflammatory bowel disease phenotype could not be predicted. Tryptophan, valine, and histidine levels were positively associated with more extended disease in UC patients (P < .05)., Conclusions: Fecal amino acids may enhance understanding of the role of host-microbial interactions in the pathophysiology of IBD and may evolve into biomarkers for pediatric IBD diagnostic and personalized medicine., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

A one-step analysis method was developed for four types of amino acids using a microfluidic paper-based analytical device fabricated from chromatography filtration paper and laminate films. Aminoacyl-tRNA synthetase was used to detect each amino acid. The obtained laminated paper-based analytical device (LPAD) contained four enzymatic reaction areas. Colorimetric detection was performed based on the molybdenum blue reaction. A model method for the simple, easy, and simultaneous detection of several amino acid concentrations was suggested, in contrast to the conventional methods such as HPLC or LC-MS. The method provided a selective quantification at the ranges of 3.6-100 μM for tryptophan, 10.1-100 μM for glycine, 5.9-100 μM for histidine and 5.6-100 μM for lysine with a detection limit of 1.1 μM, 3.3 μM, 1.9 μM and 1.8 μM, respectively. LPAD fabrication was considerably simple, and the subsequent detection process was easy and required a short period of time (within 15 min)., (© 2022. The Author(s).)

Histidine (His) is an essential amino acid that plays an important biological role and associated with various pathological conditions. A simple and reliable method for the determination of endogenous histidine in human saliva was optimized and validated. The analyte was separated from the saliva matrix by cation exchange chromatography and detected fluorimetrically (λ ex /λ em  = 360/440 nm) after online, specific post-column derivatization (PCD) reaction with o-phthalaldehyde. The chemical and instrumental variables of the post-column reaction were optimized using Box-Behnken experimental design to achieve maximum sensitivity. Method validation was carried out employing the total-error concept. Histidine could be analyzed reliably in the range of 0.5-5.0 μΜ, with an LOD (S/N = 3) of 50 nM. Monte Carlo simulations and capability analysis were used to investigate the ruggedness of the PCD reaction. The sampling strategy, sample preparation and stability were also investigated. Seventeen saliva samples were successfully analyzed with histidine levels being in the range of 2.7-19.5 μΜ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The present study aimed to report a novel electrochemical sensor through electropolymerization of o -aminophenol ( o -AP) and m -dihydroxy benzene ( m -DB) as monomers on the surface of the glassy carbon electrode (GCE) for the determination of histidine (His) as a template molecule. The developed sensor exhibited satisfactory sensitivity and high selectivity, and also offered a linear range between 0.005 and 10.0 μM with a detection limit of 0.9 nM. Finally, it is worth mentioning that we also aimed at employing the proposed sensor for the detection of His in blood serum samples.

A novel kind of chiral open-tubular (OT) column was established with homochiral zeolitic imidazolate framework-8 nanomaterials using L-histidine as the chiral carbon center (L-His-ZIF-8). The morphologies of L-His-ZIF-8 nanoparticles and chiral OT column were characterized by scanning electron microscopy. The effects of L-His-ZIF-8 concentrations, pH values, and concentrations of the running buffer on the resolution of the selected chiral compounds were investigated based on miniaturized capillary electrochromatography with amperometric detection system (mini-CEC-AD), respectively. The separation performances of the prepared L-His-ZIF-8@OT chiral columns were explored under the optimal conditions, and the RSDs of run-to-run, day-to-day, and column-to-column reproducibility were less than 6.7% using salbutamol raceme as the model enantiomers. The prepared chiral OT columns have been successfully applied to the enantioseparation of one pair of amino acid enantiomers, two pairs of racemic drugs, and three pairs of neurotransmitter enantiomers. Under the optimum conditions, the prepared OT columns were applied to real-world sample analysis of salbutamol aerosol. The limits of detection of salbutamol raceme were 0.90 μg·mL -1 (S/N = 3), and the recovery was 80.4-82.7%. The assay results indicated that this kind of chiral OT column modified with homochiral L-His-ZIF-8 possesses good reproducibility and stability. This developed mini-OT-CEC-AD system has some attractive characteristics of sensitivity and low cost, providing a potential way for the separation of chiral compounds., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Histamine is a biogenic amine that is formed from histidine by action of the enzyme histidine decarboxylase and can be toxic at high intakes. Thus, the quantification of these analytes in foods constitutes a significant axis of food safety. In this study we present the development, validation and application of a new method for the determination of histamine and its precursor histidine in fish products and oriental sauces. The analytes were separated rapidly through a cation exchange column using an acidic mobile phase (7 mmol L -1 nitric acid) and reacted downstream with o-phthalaldehyde in post-column mode in the absence of nucleophilic reagents. The derivatives were detected spectrofluorimetrically at λ ex /λ em.  = 360/440 nm. Following investigation of the chromatographic and post-column conditions, the method was validated as for its intended applications. The limits of detection were 0.16 and 0.17 μmol L -1 for histidine and histamine respectively (ca. 0.1 mg kg -1 ) and the precision was better than 5%. Various food samples were successfully analyzed without matrix interferences following minimal pretreatment. The percent recoveries ranged between 91.3 and 117.9%., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An interesting phenomenon is described that the fluorescence signal of poly(adenine) (A) DNA-templated gold nanoclusters (AuNCs) is greatly improved in the presence of L-histidine by means of L-histidine-DNA interaction. The modified nanoclusters display strong fluorescence emission with excitation/emission maxima at 290/475 nm. The fluorescence quantum yield (QY) is improved from 1.9 to 6.5%. Fluorescence enhancement is mainly ascribed to the L-histidine-DNA interaction leading to conformational changes of the poly(A) DNA template, which offer a better microenvironment to protect AuNCs. The assay enables L-histidine to be determined with good sensitivity and a linear response that covers the 1 to 50 nM L-histidine concentration range with a 0.3 nM limit of detection. The proposed method has been applied to the determination of imidazole-containing drugs in pharmaceutical samples. A turn-on fluorescent method has been designed for the sensitive detection of L-histidine as well as imidazole-containing drugs on the basis of the L-histidine-DNA interaction.

Antimicrobial peptides (AMPs) are part of the innate immune system of many species. AMPs are short sequences rich in charged and non-polar residues. They act on the lipid phase of the plasma membrane without requiring membrane receptors. Polybia-MP1 (MP1), extracted from a native wasp, is a broad-spectrum bactericide, an inhibitor of cancer cell proliferation being non-hemolytic and non-cytotoxic. MP1 mechanism of action and its adsorption mode is not yet completely known. Its adsorption to lipid bilayer and lytic activity is most likely dependent on the ionization state of its two acidic and three basic residues and consequently on the bulk pH. Here we investigated the effect of bulk acidic (pH 5.5) and neutral pH (7.4) solution on the adsorption, insertion, and lytic activity of MP1 and its analog H-MP1 to anionic (7POPC:3POPG) model membrane. H-MP1 is a synthetic analog of MP1 with lysines replaced by histidines. Bulk pH changes could modulate this peptide efficiency. The combination of different experimental techniques and molecular dynamics (MD) simulations showed that the adsorption, insertion, and lytic activity of H-MP1 are highly sensitive to bulk pH in opposition to MP1. The atomistic details, provided by MD simulations, showed peptides contact their N-termini to the bilayer before the insertion and then lay parallel to the bilayer. Their hydrophobic faces inserted into the acyl chain phase disturb the lipid-packing.

An enzyme showing l-histidine oxidase (HisO) activity by the formation of hydrogen peroxide was newly purified from Achromobacter sp. TPU 5009. This enzyme was found to be a heterodimer of two proteins (molecular mass, 53.8 and 58.3 kDa), the partial determination of which indicated they are homologs of l-histidine ammonia-lyase (AchHAL) and urocanate hydratase (AchURO). The enzyme was stable in a pH range of 5.0-11.0, with >90% of the original activity maintained below 60°C at pH 7.0. To characterize AchHAL and AchURO, each of their genes was cloned and expressed in a heterologous expression system. Heterologous AchHAL catalyzed the elimination of the α-amino group of l-histidine to urocanate and ammonia, while heterologous AchURO catalyzed the hydration of urocanate to imidazolone propionate. Since imidazolone propionate is highly unstable in the presence of oxygen at neutral pH, it was immediately decomposed and hydrogen peroxide was non-enzymatically produced. Our results indicate that this natural enzyme showing apparent HisO activity is composed of AchHAL and AchURO, which formed hydrogen peroxide after the spontaneous decomposition of imidazolone propionate., (Copyright © 2021. Published by Elsevier B.V.)

A chemoselective as well as enantioselective fluorescent probe has been developed to determine both the concentration and enantiomeric composition of the biologically important amino acid histidine by measuring the fluorescence responses when excited at two different wavelengths.

Specific and expeditious identification and enrichment of target proteins in living cells is often a challenging task. The hexahistidine (6His) tag is frequently used to label artificially engineered proteins produced in prokaryotic or eukaryotic cells. Utilizing the interaction between 6His-tag and nitrilotriacetic acid (NTA) mediated by divalent metal ions (Ni 2+ , Cu 2+ , Zn 2+ or Co 2+ ), we designed and synthesized a series of Nap-G/Biotin/ANA-FFpYGK-NTA probes that, assisted by alkaline phosphatase (ALP), self-assemble into nanofibers. The probe consists of an NTA group that specifically binds to 6His-tag, an FFpY group that promotes self-assembly facilitated by ALP, and a hydrophobic (Nap-G/ANA/Biotin) capping group for various applications. We demonstrate that the ANA-FFpYGK-NTA(Ni 2+ ) nanofibers are fit for real-time tracking of His-tagged protein in living cells, and the Biotin-FFpYGK-NTA(Ni 2+ ) nanofibers are for isolating His-tagged proteins and other proteins that they interact with.

A comprehensive review of optical biosensors for the detection of biomarkers associated with rheumatoid arthritis (RA) is presented here, including microRNAs (miRNAs), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), interleukin-6 (IL-6) and histidine, which are biomarkers that enable RA detection and/or monitoring. An overview of the different optical biosensors (based on fluorescence, plasmon resonances, interferometry, surface-enhanced Raman spectroscopy (SERS) among other optical techniques) used to detect these biomarkers is given, describing their performance and main characteristics (limit of detection (LOD) and dynamic range), as well as the connection between the respective biomarker and rheumatoid arthritis. It has been observed that the relationship between the corresponding biomarker and rheumatoid arthritis tends to be obviated most of the time when explaining the mechanism of the optical biosensor, which forces the researcher to look for further information about the biomarker. This review work attempts to establish a clear association between optical sensors and rheumatoid arthritis biomarkers as well as to be an easy-to-use tool for the researchers working in this field.

A laminated paper-based analytical device (LPAD) for histidine detection was fabricated from a chromatography filtration paper and laminate films. Histidine recognition was effected by histidyl-tRNA synthetase (HisRS), and its detection was signaled colorimetrically based on the molybdenum blue reaction. The analytical conditions and detectable concentration range of histidine were examined. The method provided selective quantification from 1 to 100 μM histidine. LPAD fabrication is considerably simple, involving only the craft-cutting of the chromatography filtration paper and laminate film, and is cost-effective.

Two-state ratiometric biosensors change conformation and spectral properties in response to specific biochemical inputs. Much effort over the past two decades has been devoted to engineering biosensors specific for ions, nucleotides, amino acids, and biochemical potentials. The utility of these biosensors is diminished by empirical errors in fluorescence-ratio signal measurement, which reduce the range of input values biosensors can measure accurately. Here, we present a formal framework and a web-based tool, the SensorOverlord, that predicts the input range of two-state ratiometric biosensors given the experimental error in measuring their signal. We demonstrate the utility of this tool by predicting the range of values that can be measured accurately by biosensors that detect pH, NAD + , NADH, NADPH, histidine, and glutathione redox potential. The SensorOverlord enables users to compare the predicted accuracy of biochemical measurements made with different biosensors, and subsequently select biosensors that are best suited for their experimental needs.

Due to its key roles in regulating the occurrence and development of cancer, protein histidine phosphorylation has been increasingly recognized as an important form of post-translational modification in recent years. However, large-scale analysis of histidine phosphorylation is much more challenging than that of serine/threonine or tyrosine phosphorylation, mainly because of its acid lability. In this study, MoS 2 -Ti 4+ nanomaterials were synthesized using a solvothermal method and taking advantage of the electrostatic adsorption between MoS 2 nanosheets and Ti 4+ . The MoS 2 -Ti 4+ nanomaterials have the advantage of the combined affinity of Ti 4+ and Mo toward phosphorylation under medium acidic conditions (pH = 3), which is crucial for preventing hydrolysis and loss of histidine phosphorylation during enrichment. The feasibility of using the MoS 2 -Ti 4+ nanomaterial for phosphopeptide enrichment was demonstrated using mixtures of β-casein and bovine serum albumin (BSA). Further evaluation revealed that the MoS 2 -Ti 4+ nanomaterial is capable of enriching synthetic histidine phosphopeptides from 1000 times excess tryptic-digested HeLa cell lysate. Application of the MoS 2 -Ti 4+ nanomaterials for large-scale phosphopeptide enrichment results in the identification of 10 345 serine, threonine, and tyrosine phosphosites and the successful mapping of 159 histidine phosphosites in HeLa cell lysates, therefore indicating great potential for deciphering the vital biological roles of protein (histidine) phosphorylation.

Background and Aims: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease., Methods: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces., Results: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease., Conclusions: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease., Podcast: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Small-scale models that simulate large-scale freezing of bulk drug substance of biopharmaceuticals are highly needed to define freezing and formulation parameters based on process understanding. We evaluated a novel scale-down device (SDD), which is based on a specially designed insulation cover, with respect to changes in concentration after freezing, referred to as cryoconcentration, and 3D temperature profiles. Furthermore, the effect of the initial monoclonal antibody (mAb) concentration on cryoconcentration was addressed., Methods: 2 L and 125 mL bottles were utilized. Temperatures were mapped using type T thermocouples. Frozen blocks were cut and mAb and histidine concentrations were analysed by HPLC. In addition, concentration- and temperature-dependent viscosities were measured., Results: 3D freezing profiles in the SDD were comparable to large-scale bottles. The SDD accurately predicted cryoconcentration of both mAb and histidine of large-scale freezing. Concentric changes in concentration were evident as well as an unforeseen diluted core at the last point to freeze. At low initial mAb concentration cryoconcentration was substantial, while high initial mAb concentration suppressed cryoconcentration almost completely., Conclusion: The novel SDD gives detailed insights into large-scale freezing of mAb solutions using only a fraction of the simulated volume. It is a promising material- and cost-saving tool to understand large-scale freezing processes.

The polyhistidine tag (His-tag) is one of the most popular protein tags used in the life sciences. Traditionally, the detection of His-tagged proteins relies on immunoblotting with anti-His antibodies. This approach is laborious for certain applications, such as protein purification, where time and simplicity are critical. The His-tag can also be directly detected by metal ion-loaded nickel-nitrilotriacetic acid-based chelator heads conjugated to fluorophores, which is a convenient alternative method to immunoblotting. Typically, such chelator heads are conjugated to either green or red fluorophores, the detection of which requires specialized excitation sources and detection systems. Here, we demonstrate that post-run staining is ideal for His-tag detection by metal ion-loaded and fluorescently labeled chelator heads in PAGE and blot membranes. Additionally, by comparing the performances of different chelator heads, we show how differences in microscopic affinity constants translate to macroscopic differences in the detection limits in environments with limited diffusion, such as PAGE. On the basis of these results, we devise a simple approach, called UVHis-PAGE, that uses metal ion-loaded and fluorescently labeled chelator heads to detect His-tagged proteins in PAGE and blot membranes. Our method uses a UV transilluminator as an excitation source, and the results can be visually inspected by the naked eye., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Raducanu et al.)

Selenoneine is a novel organic selenium compound markedly found in the blood, muscles, and other tissues of fish. This study aimed to determine whether selenoneine attenuates hepatocellular injury and hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice lacking farnesoid X receptor (FXR) were used as a model for fatty liver disease, because they exhibited hepatomegaly, hepatic steatosis, and hepatic inflammation. Fxr -null mice were fed a 0.3 mg Se/kg selenoneine-containing diet for four months. Significant decreases in the levels of hepatomegaly, hepatic damage-associated diagnostic markers, hepatic triglycerides, and total bile acids were found in Fxr -null mice fed with a selenoneine-rich diet. Hepatic and blood clot total selenium concentrations were 1.7 and 1.9 times higher in the selenoneine group than in the control group. A marked accumulation of selenoneine was found in the liver and blood clot of the selenoneine group. The expression levels of oxidative stress-related genes ( heme oxygenase 1 ( Hmox1 ), glutathione S-transferase alpha 1 ( Gsta1 ), and Gsta2 ), fatty acid synthetic genes ( stearoyl CoA desaturase 1 ( Scd1 ) and acetyl-CoA carboxylase 1 ( Acc1 )), and selenoprotein ( glutathione peroxidase 1 ( Gpx1 ) and selenoprotein P ( Selenop )) were significantly decreased in the selenoneine group. These results suggest that selenoneine attenuates hepatic steatosis and hepatocellular injury in an NAFLD mouse model.

Histamine, one of the most toxic and commonly encountered biogenic amines (BA) in food, is produced by the microbial decarboxylation of histidine. It may accumulate at high concentrations in fish and fermented food. Cheese has some of the highest histamine concentrations, the result of the histidine-decarboxylase activity of certain lactic acid bacteria (LAB). The present work describes the nucleotide sequence and transcriptional organization of the gene cluster responsible for histamine biosynthesis (the HDC cluster) in Lactobacillus vaginalis IPLA 11064 isolated from cheese. The influence of histidine availability and pH on histamine production and the expression of the HDC cluster genes is also examined. As expected, the results suggest that the production of histamine under acidic conditions improves cell survival by maintaining the cytosol at an appropriate pH. However, the transcriptional regulation of the HDC cluster is quite different from that described in other dairy histamine-producing LAB, probably due to the lack of a termination-antitermination system in the histidyl-tRNA synthetase gene (hisS)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Due to the disruption by other nonanalyte factors, single-emission probes have been limited in complicated detecting systems. In this work, a pH-modulated luminescence chameleon system based on lanthanide-based MOF (Eu 3+ @Mn-MOF), with stable structure and miraculous dual-emitting fluorescent properties, was synthesized by a postsynthetic modification (PSM) strategy of a simple hydrothermal and agitation method. Amazingly, not only can the Eu 3+ @Mn-MOF emit a broad emission at 500 nm attributed to the ligand-based fluorescence emission but it can also exhibit the characteristic emission of Eu 3+ ions responding to the antenna effect. Moreover, the Eu 3+ @Mn-MOF displays an interesting luminescence color transition between acidic and basic solutions. Inspired by this phenomenon, a pH-modulated luminescence chameleon system was first constructed and employed to detect histidine, a kind of basic amino acid for a variety of biological matters, causing a unique fluorescence signal of the ratio-dependent color to change from yellow to light pink which differs from the color change of other water-soluble amino acids. Therefore, Eu 3+ @Mn-MOF can be as a practical pH-modulated luminescence chameleon system chemsensor for sensing histidine with low detection limit, high sensitivity, and rapid sensing time. In conclusion, the postsynthetic modified Eu 3+ @Mn-MOF has outstanding applications in the fields of chemical detection and human health.

A far-red fluorescence "off-on" sensing strategy is described for sequential ratiometric determination of Cu 2+ and L-histidine (L-His) based on fluorescence resonance energy transfer (FRET) system. N,S,P co-doped carbon dots (N,S,P-CDs) and N-acetyl-L-cysteine functionalized gold nanoclusters (NAC-AuNCs) are used in the FRET system, which serve as energy donor and acceptor, respectively. After adding NAC-AuNCs into the solution of N,S,P-CDs, the fluorescence of N,S,P-CDs is effectively quenched, while the far-red fluorescence of NAC-AuNCs appears. Cu 2+ can decrease fluorescence of NAC-AuNCs, and then L-His can effectively recover the fluorescence of NAC-AuNCs. The possible reason is that the stronger affinity between Cu 2+ and L-His can pull Cu 2+ away from the surface of NAC-AuNCs. Through it all, the emission intensity of N,S,P-CDs remains nearly constant, so the ratio of fluorescence intensities at 485 and 625 nm exhibits a linear correlation to the Cu 2+ and L-His concentration, respectively. The sensing platform shows good selectivity towards Cu 2+ and L-His with a linear range of 0.65-26.58 μM and 3.13-56.25 μM and determination limits of 0.50 μM and 0.374 μM, respectively. The proposed method has been successfully used for Cu 2+ and L-His determination in real samples with satisfying results. Graphical abstract.

Bile acid (BA) imbalance may be directly associated with gastric cancer and indirectly influence stomach carcinogenesis via overexpression of histidine decarboxylase (HDC), which converts histidine (His) into histamine (HIST). Moreover, the progression of gastric cancer, could change the gut microbiome, including bacteria spp. that produce secondary BAs. Gastric juice has various metabolites that could indicate gastric cancer-related stomach conditions. Therefore, profiling of HIST, His, and BAs in gastric juice is crucial for understanding the etiological mechanisms of gastric cancer. We used a profiling method to simultaneously determine targeted metabolites in gastric juice using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We successfully analyzed 70 human gastric juice samples from patients with chronic superficial gastritis (CSG, n = 20), intestinal metaplasia (IM, n = 12), and gastric cancer (n = 38). Furthermore, we investigated the relevance between BA metabolism and gastric cancer. There were statistical differences in the metabolism of cholic acid (CA) into deoxycholic acid (DCA) based on the progression of CSG into IM and gastric cancer. Hence, the progression of gastric cancer might be related to the alterations in gut microbiome composition. We provide insight into the etiological mechanisms of the progression of gastric cancer and biomarkers to diagnose and treat gastric cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated by proteolysis of the N-terminus, which exposes a tethered ligand that interacts with the receptor. Numerous studies have focused on the signaling pathways mediated by PARs. However, the structural basis for initiation of these pathways is unknown. Here, we describe a strategy for the expression and purification of PAR4. This is the first PAR family member to be isolated without stabilizing modifications for biophysical studies. We monitored PAR4 activation with histidine hydrogen-deuterium exchange. PAR4 has nine histidines that are spaced throughout the protein, allowing a global view of solvent accessible and nonaccessible regions. Peptides containing each of the nine His residues were used to determine the t 1/2 for each His residue in apo or thrombin-activated PAR4. The thrombin-cleaved PAR4 exhibited a 2-fold increase ( p > 0.01) in t 1/2 values observed for four histidine residues (His 180 , His 229 , His 240 , and His 380 ), demonstrating that these regions have decreased solvent accessibility upon thrombin treatment. In agreement, thrombin-cleaved PAR4 also was resistant to thermolysin digestion. In contrast, the rate of thermolysin proteolysis following stimulation with the PAR4 activation peptide was the same as that of unstimulated PAR4. Further analysis showed the C-terminus is protected in thrombin-activated PAR4 compared to uncleaved or agonist peptide-treated PAR4. The studies described here are the first to examine the tethered ligand activation mechanism for a PAR family member biophysically and shed light on the overall conformational changes that follow activation of PARs by a protease.

A simple, green and nondestructive method based on terahertz fingerprint peaks has been developed for rapid in situ analysis of l-histidine and α-lactose in dietary supplements. Fingerprint absorption peaks of l-histidine and α-lactose located at 0.77 and 0.53 THz could be directly used for identification and quantitation of these analytes in commercial dietary supplements. Compared with the partial least squares regression model (PLSR), the linear least squares regression (LLSR) method based on peak areas presented better performance, with the linear correlation coefficients of 0.9899 and 0.9910 for l-histidine and α-lactose, respectively. Furthermore, analysis time per sample can be shortened to less than 1 min due to the narrower spectral acquisition region. The accuracies were 94.8-110% and 98.9-110%, comparable to those of ion chromatography for l-histidine and high-performance liquid chromatography for α-lactose. The results presented great potential of the developed method for rapid in situ analysis of nutrients in dietary supplements., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A fluorometric assay for histidine (His) is described. It is based on the inhibitory effect of His on nanocubes consisting of cobalt-containing Prussian Blue analog (CoFe NCbs), which have a strong oxidation effect on thiamine (THI) in the presence of NaOH. THI is nonfluorescent but the oxidized form (thiochrome; ThC) has a strong blue fluorescence, with excitation/emission maxima at 370/445 nm. His inhibits the oxidation effect of the CoFe NCbs due to the strong interaction between its imidazole side chain and the amino groups of the CoFe NCbs. This method is fast and has good sensitivity and selectivity. The lower detection limit is 14.3 nM of His, the linear range extends from 0.05 to 2.5 μM, and the relative standard deviation is calculated to be 1.5%. The method was successfully employed to quantify His in spiked serum samples. Graphical abstractSchematic representation of cobalt-containing Prussian Blue nanocubes (CoFe NCbs)-thiamine (THI)-based fluorometric assay for Histine (His). His inhibits the generation of thiochrome (ThC; the oxidized form of THI). The detection limit is 14.3 nM with the linear range of 0.05-2.5 μM.

In the current study, an electrochemical biosensing signal amplification system was utilized with thionine-chitosan-gold nanoparticles (Chit-GNPs) that absorbed horseradish peroxidase (HRP) and anti-His tagged protein monoclonal antibody derived from Balb/c mice. In addition, transmission electron microscopy (TEM) was used to characterize the nanogold solution and atomic force microscopy (AFM) was used to characterize the sensor assembly. To evaluate the quality of the immunosensor, the amperometric I-t curve method was applied to determine His-IL23 in PBS. The results indicated that the response current exhibited an optimal linear correlation with the His-IL23 concentration that ranged from 0.01 to 10 3  ng/ml. The lowest detection limit was noted at 3.3 pg/ml (S/N = 3). The linear equation was deduced as follows: △I = 0.02lgC + 0.037 (R 2  = 0.9628). Moreover, it was validated with high sensitivity, reproducibility and rapid response. Apparently, the immunosensor may be a very useful tool for the detection and quantification of His-tagged proteins. In addition, the signal amplification system can be used for the preparation of other immunosensors and to assist in bioassays.

We recently found that [Eu(pda) 2 ] - (pda: 1,10-phenanthroline-2,9-dicarboxylic acid), which has an achiral structure in crystals, exhibits circularly polarized luminescence (CPL) in aqueous solutions containing chiral amino acids such as arginine and histidine. CPL measurements were performed for agar gel, which includes an aqueous solution of [Eu(pda) 2 ] - and chiral arginine or histidine. The spectral shape, concentration, and pH dependences on CPL intensity in the agar gels were very close to those in aqueous solutions, indicating that the CPL of the Eu III complex in the agar gels was induced by mechanism similar to that in aqueous solutions. We performed spatially resolved CPL measurements using a laboratory-built microscopic CPL spectroscopic system for agar-gel samples, where d- and l- amino acids were separately dispersed. We successfully recorded CPL imaging maps showing spatial dispersions of d- and l-amino acid in the agar gels., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, quartz crystal microbalance (QCM) biosensor is prepared for the detection of l-histidine by attachment of l-histidine imprinted poly(EGDMA-MAH/Cu(II)) nanoparticles on QCM electrode. The imprinted nanoparticles with the size of 86.43 nm were synthesized via miniemulsion polymerization reaction. Prepared QCM sensors were characterized with ellipsometer, contact angle measurements and FTIR. The thickness measurements demonstrated that the particle thin films were almost monolayer. l-histidine solutions with a concentration range between 6.44 μM and 225.6 μM were introduced to QCM system to determine the adsorption kinetics. Selectivity of the l-histidine imprinted nanoparticles were examined using d-histidine and l-tryptophan as competitor molecules. l-histidine imprinted QCM biosensors was also used for RNAase, lysozyme, cytochrome-C and BSA to investigate the competitive adsorption of surface histidine exposed proteins.