A paper-based point-of-care device for the detection of cysteine using gold nanoparticles from whole blood.

We present a colorimetric probe based on polyvinylpyrrolidone-capped gold nanoparticles (PVP-AuNPs) that is sensitive and selective for cysteine (Cys). A microfluidic paper-based analytical device (µ-PAD) with embedded dried PVP-AuNPs at the polyethersulfone (PES) paper surface is used for Cys detection. When thiol molecules attach to PVP-AuNPs in the presence of Cys, they clump together, and this causes the solution's color to shift from red to blue within 5 minutes. The device is capable of detecting Cys levels between 1.0 µM and 50.0 µM with a limit of detection (LOD) of 0.2 µM under optimized conditions. The stability of the µ-PAD was tested for 100 days, demonstrating re-dispersibility to detect Cys levels in blood. Dried PVP-AuNP-µPADs were integrated with blood plasma separation modules for point-of-care (POC) Cys detection. Consequently, the device shows potential as a self-sustaining, quantification platform with a recovery percentage ranging from 98.44 to 111.9 in clinical samples.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Intact quantitation of cysteine-conjugated antibody-drug conjugates using native mass spectrometry.

RATIONALE: A common strategy for antibody-drug conjugate (ADC) quantitation from in vivo study samples involves measurement of total antibody, conjugated ADC, and free payload concentrations using multiple reaction monitoring (MRM) mass spectrometry. This not only provides a limited picture of biotransformation but can also involve lengthy method development. Quantitation of ADCs directly at the intact protein level in native conditions using high-resolution mass spectrometers presents the advantage of measuring exposure readout as well as monitoring the change in average drug-to-antibody ratio (DAR) and in vivo stability of new linker payloads with minimal method development. Furthermore, site-specific cysteine-conjugated ADCs often rely on non-covalent association to retain their quaternary structure, which highlights the unique capabilities of native mass spectrometry (nMS) for intact ADC quantitation. METHODS: We developed an intact quantitation workflow involving three stages: automated affinity purification, nMS analysis, and data processing in batch fashion. The sample preparation method was modified to include only volatile ion-pairing reagents in the buffer systems. A capillary size-exclusion chromatography (SEC) column was coupled to a quadrupole time-of-flight high-resolution mass spectrometer for high-throughput nMS analysis. Samples from two mouse pharmacokinetic (PK) studies were analyzed using both intact quantitation workflow and the conventional MRM-based approach. RESULTS: A linear dynamic range of 5-100 µg/mL was achieved using 20 µL of serum sample volume. The results of mouse in vivo PK measurement using the intact quantitation workflow and the MRM-based approach were compared, revealing excellent method agreement. CONCLUSIONS: We demonstrated the feasibility of utilizing nMS for the quantitation of ADCs at the intact protein level in preclinical PK studies. Our results indicate that this intact quantitation workflow can serve as an alternative generic method for high-throughput analysis, enabling an in-depth understanding of ADC stability and safety in vivo.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Effects of non-essential protein on D-glucose to control diabetes: DFT approach.

Diabetes is a disease found in every 1 out of 4 people in the world. The glucose molecule is one of the sources of energy in the body and the lack of the digestion of glucose causes diabetes type 1 and type 2. Arginine and cysteine are nonessential amino acids that contain sulfur and help maintain the metabolisms of humans. We explored the glucose-arginine (Glc-arg) and glucose-cysteine (Glc-cys) molecules by finding their structural properties, electronic properties, chemical reactivity, mechanical strength, and transport properties because these non-essential amino acid molecules inhibit glucose-stimulated insulin secretion. Density functional theory (DFT) has been implemented to study all the properties of Glc-arg and Glc-cys using SIESTA software. Glucose-arginine (Glc-arg) inhibits a large percentage of glucose secretion and shows high chemical reactivity.

Amino Acids and Lipids Associated with Long-Term and Short-Term Red Meat Consumption in the Chinese Population: An Untargeted Metabolomics Study.

Red meat (RM) consumption is correlated with multiple health outcomes. This study aims to identify potential biomarkers of RM consumption in the Chinese population and evaluate their predictive ability. We selected 500 adults who participated in the 2015 China Health and Nutrition Survey and examined their overall metabolome differences by RM consumption by using elastic-net regression, then evaluate the predictivity of a combination of filtered metabolites; 1108 metabolites were detected. In the long-term RM consumption analysis 12,13-DiHOME, androstenediol (3α, 17α) monosulfate 2, and gamma-Glutamyl-2-aminobutyrate were positively associated, 2-naphthol sulfate and S-methylcysteine were negatively associated with long-term high RM consumption, the combination of metabolites prediction model evaluated by area under the receiver operating characteristic curve (AUC) was 70.4% (95% CI: 59.9-80.9%). In the short-term RM consumption analysis, asparagine, 4-hydroxyproline, and 3-hydroxyisobutyrate were positively associated, behenoyl sphingomyelin (d18:1/22:0) was negatively associated with short-term high RM consumption. Combination prediction model AUC was 75.6% (95% CI: 65.5-85.6%). We identified 10 and 11 serum metabolites that differed according to LT and ST RM consumption which mainly involved branch-chained amino acids, arginine and proline, urea cycle and polyunsaturated fatty acid metabolism. These metabolites may become a mediator of some chronic diseases among high RM consumers and provide new evidence for RM biomarkers.

Extending the HSA-Cys34-Adductomics Pipeline to Modifications at Lys525.

We previously developed an adductomics pipeline that employed nanoflow liquid chromatography and high-resolution tandem mass spectrometry (nLC-HR-MS/MS) plus informatics to perform an untargeted detection of modifications to Cys34 in the tryptic T3 peptide of human serum albumin (HSA) (21ALVLIAFAQYLQQC34PFEDHVK41). In order to detect these peptide modifications without targeting specific masses, the pipeline interrogates MS2 ions that are signatures of the T3 peptide. The pipeline had been pilot-tested with archived plasma from healthy human subjects, and several of the 43 Cys34 adducts were highly associated with the smoking status. In the current investigation, we adapted the pipeline to include modifications to the ε-amino group of Lys525─a major glycation site in HSA─and thereby extend the coverage to products of Schiff bases that cannot be produced at Cys34. Because trypsin is generally unable to digest proteins at modified lysines, our pipeline detects miscleaved tryptic peptides with the sequence 525KQTALVELVK534. Adducts of both Lys525 and Cys34 are measured in a single nLC-HR-MS/MS run by increasing the mass range of precursor ions in MS1 scans and including both triply and doubly charged precursor ions for collision-induced dissociation fragmentation. For proof of principle, we applied the Cys34/Lys525 pipeline to archived plasma specimens from a subset of the same volunteer subjects used in the original investigation. Twelve modified Lys525 peptides were detected, including products of glycation (fructosyl-lysine plus advanced-glycated-end products), acetylation, and elimination of ammonia and water. Surprisingly, the carbamylated and glycated adducts were present at significantly lower levels in smoking subjects. By including a larger class of in vivo nucleophilic substitution reactions, the Cys34/Lys525 adductomics pipeline expands exposomic investigations of unknown human exposure to reactive electrophiles derived from both exogenous and endogenous sources.

A simple and accurate HFCF-UF method for the analysis of homocysteine, cysteine, cysteinyl-glycine, and glutathione in human blood.

The presence of reduced aminothiols, including homocysteine (Hcy), cysteine (Cys), cysteinyl-glycine (CG), and glutathione (GSH), is significantly increased in the pathological state. However, there have been no reports on the relationship between reduced aminothiols (Hcy, Cys, CG, and GSH) and different genders, ages, and drug combinations in human blood. The accurate quantification of these reduced thiols in biological fluids is important for monitoring some special pathological conditions of humans. However, the published methods typically not only require cumbersome and technically challenging processing procedures to ensure reliable measurements, but are also laborious and time-consuming, which may disturb the initial physiological balance and lead to inaccurate results. We developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation coupled with a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method and used it to determine four reduced aminothiols (Hcy, Cys, CG, and GSH) in human blood for the first time. A total of 96 clinical patients were enrolled in our study. The influence of different genders, ages, and drug combinations on the levels of four reduced thiols in human blood was also discussed by SPSS 24.0. The sample preparation was simplified to a single 5 min centrifugation step in a sealed system that did not disturb the physiological environment. The validation parameters for the methodological results were excellent. The procedure was successfully applied to monitoring the concentrations of four reduced aminothiols (Hcy, Cys, CG, and GSH) in 96 clinical blood samples. There were no significant differences in Hcy, Cys, CG, or GSH for the different genders, ages, or combinations with methotrexate or vancomycin (P > 0.05). However, there was a significant increase in Hcy concentration in patients treated with valproic acid who were diagnosed with epilepsy (p=0.0007). It is advisable to measure reduced Hcy level in patients taking valproic acid. The developed HFCF-UF method was simple and accurate. It can be easily applied in clinical research to evaluate oxidative stress in further study.

Peroxidase-mimetic activity of FeOCl nanosheets for the colorimetric determination of glutathione and cysteine.

For the first time the enzyme mimic activity of iron oxychloride (FeOCl) nanosheets has been studied. The intrinsic peroxidase-mimetic activity of the nanosheets in the presence of H2O2 was approved by the efficient oxidation of tetramethylbenzidine (TMB). The Michaelis-Menten constant of the nanosheets toward TMB was about six times lower than that of natural horseradish peroxidase. The superiority of the nanosheets' catalytic property ascribes to their H2O2 activation ability. Based on the inhibition of the nanozymes' catalytic reaction, an assay was developed for the quantitative measurement of glutathione (GSH) and cysteine (Cys). The linear range for both biomolecules was over the range of 3-33 µM. The LOD values (3σ/slope) for GSH and Cys were 2.23 µM and 2.76 µM, respectively. Importantly, we succeeded in colorimetric discrimination of GSH and Cys kinetically. We achieved high selectivity toward GSH and Cys. This work extends the feasibility of using FeOCl as nanozymes to construct biosensors, colorimetric probes for medical diagnosis, and nanozyme-based cancer therapy.

Nanozyme based on CoFe2O4 modified with MoS2 for colorimetric determination of cysteine and glutathione.

A nanozyme based on CoFe2O4 modified with MoS2 was constructed for colorimetric determination of cysteine (Cys) and glutathione (GSH). Firstly, ferrite CoFe2O4 is synthesized, and it is then modified by MoS2 to form a flower-like polymer (MoS2@CoFe2O4). In the presence of H2O2, a redox interaction takes place, and the resulting hydroxyl promoted a colorimetric conversion from colorless to blue in the presence of 3,3',5,5'-tetramethylbenzidine (TMB). However, once Cys or GSH is added, they are capable to compete with the interaction of the hydroxyl with TMB, resulting in an inhibition of the colorimetric conversion. The colorimetric distinction is sensitive to the amount of target. The results obtained proved that the catalytic efficiency of MoS2@CoFe2O4 is 4.4-fold and 1.8-fold to that of MoS2 and CoFe2O4. Meanwhile, the Km values to TMB and H2O2 are 0.067 and 0.048 mM, respectively, which are 6.5-fold and 77-fold, respectively smaller than those of natural peroxidase such as HPR. This indicates that the MoS2@CoFe2O4 possesses a favorable interaction affinity. Additionally, the colorimetric distinction caused by the competition between TMB and cysteine or glutathione is obvious. The signal responses to cysteine and glutathione are linear in the range 0.5~15 µM and 0.5~35 µM, and the LODs are 0.10 and 0.21 µM, respectively. In practical assay of Cys in serum, the RSD of the sample tests is 4.6%, and the recoveries for the spiked assays are 95.3% and 96.0% with the RSD of 2.1% and 4.2%, respectively.

Metabolites Associated with Early Cognitive Changes Implicated in Alzheimer's Disease.

BACKGROUND: Understanding metabolic mechanisms associated with cognitive changes preceding an Alzheimer's disease (AD) diagnosis could advance our understanding of AD progression and inform preventive methods. OBJECTIVE: We investigated the metabolomics of the early changes in executive function and delayed recall, the earliest aspects of cognitive function to change in the course of AD development, in order to better understand mechanisms that could contribute to early stages and progression of this disease. METHODS: This investigation used longitudinal plasma samples from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort of participants who were dementia free at enrollment and enriched with a parental history of AD. Metabolomic profiles were quantified for 2,324 fasting plasma samples among 1,200 participants, each with up to three study visits, which occurred every two years. Metabolites were individually tested for association with executive function and delayed recall trajectories across age. RESULTS: Of 1,097 metabolites tested, levels of seven were associated with executive function trajectories, including an amino acid cysteine S-sulfate and three fatty acids, including erucate (22 : 1n9), while none were associated with delayed recall trajectories. Replication was attempted for four of these metabolites that were present in the Vietnam Era Twin Study of Aging (VETSA). Although none reached statistical significance, three of these associations showed consistent effectdirections. CONCLUSION: Our results suggest potential metabolomic mechanisms that could contribute to the earliest signs of cognitive decline. In particular, fatty acids may be associated with cognition in a manner that is more complex than previously suspected.

Near-infrared fluorogenic receptor for selective detection of cysteine in blood serum and living cells.

A novel near-infrared fluorescent probe, namely propane-2,2-diylbis(2-((E)-2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)-4,1-phenylene) diacrylate (BTA), was synthesized for selective detection of cysteine over other biologically significant amino acids. Upon addition of cysteine, the probe BTA displays a dramatic increase in fluorescence intensity at 715 nm along with a fast response time (4 min). The limit of detection (LOD) was calculated as 0.12 µM. In addition, the synthesized probe BTA was effectively utilized for the recognition of cysteine in blood serum and living cells.

Easy-to-Prepare Mini-Chemosensor Array for Simultaneous Detection of Cysteine and Glutathione Derivatives.

We herein propose an easy-to-prepare mini-chemosensor array constructed by two-types of off-the-shelf coumarin dyes for simultaneous classification and quantification of sulfur-containing amino acids (SCAAs) (i.e., l-cysteine, l-cystine, l-homocysteine, glutathione, and glutathione disulfide). The detection mechanism of SCAAs relied on a coordination-based sensor array (CBSA) utilizing the competitive binding among the coumarin dye, a Zn2+ ion and SCAAs. The reversible feature of the coordination bond of the coumarin-Zn2+ resulted in UV/vis spectral shifts and fluorescence enhancement in response to the analytes, offering the multianalyte detection in high accuracy. Furthermore, a mixture of glutathione and l-cysteine was successfully quantified in a sample containing human blood serum. This study would be an important example of the optical chemosensor array toward the rapid and accurate detection of biomarkers.

Identification and quantitation of hinge cysteinylation on endogenous IgG2 antibodies from human serum.

Cysteinylation is a post-translational modification (PTM) that occurs when a cysteine residue on a protein forms a disulfide bond with a terminal cysteine molecule. This PTM has been found in the hinge region of several recombinant therapeutic IgG2 antibodies, but the impact of cysteinylation on the safety and immunogenicity of therapeutics remains unclear. In this study, we characterized recombinant and endogenous IgG2 antibodies to quantify their levels of hinge cysteinylation, if present. To the best of our knowledge, this is the first study to identify and quantify hinge cysteinylation in endogenous IgG2 antibodies from healthy human serum. We used anti-IgG2 immunopurification of human serum to specifically enrich for endogenous IgG2 antibodies, and then subjected the resulting samples to Lys-C peptide mapping coupled with targeted mass spectrometry techniques. Using this analytical workflow, we found that all healthy human serum samples tested (N = 10) contained quantifiable levels of hinge cysteinylation (0.8 ± 0.3%) in their endogenous human IgG2s (IgG2-A isoform). These findings demonstrate that hinge cysteinylation in therapeutic IgG2s, at least up to a certain level, is well tolerated in humans and pose minimal safety or immunogenicity risks.

Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences.

AIMS: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects. RESULTS: Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments. The increase in GSH correlated with a decrease in γ-glutamyltranspeptidase (γ-GT) activity of the different tissues. In vitro and ex vivo experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH. CONCLUSION: s. The prominent in vivopharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress. In particular, by inhibition of γ-GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation. The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting. All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage.

Association of Plasma Total Cysteine and Anthropometric Status in 6-30 Months Old Indian Children.

High-quality protein has been associated with child growth; however, the role of the amino acid cysteine remains unclear. The aim was to measure the extent to which plasma total cysteine (tCys) concentration is associated with anthropometric status in children aged 6-30 months living in New Delhi, India. The study was a prospective cohort study including 2102 children. We calculated Z-scores for height-for-age (HAZ), weight-for-height (WHZ), or weight-for-age (WAZ) according to the WHO Child Growth Standards. We used multiple regression models to estimate the association between tCys and the anthropometric indices. A high proportion of the children were categorized as malnourished at enrolment; 41% were stunted (HAZ ≤ -2), 19% were wasted (WHZ ≤ -2) and 42% underweight (WAZ ≤ -2). Plasma total cysteine (tCys) was significantly associated with HAZ, WHZ and WAZ after adjusting for relevant confounders (p < 0.001). Low tCys (≤25th percentile) was associated with a decrease of 0.28 Z-scores for HAZ, 0.10 Z-scores for WHZ, and 0.21 Z-scores for WAZ compared to being >25th percentile. In young Indian children from low-to-middle socioeconomic neighborhoods, a low plasma total cysteine concentration was associated with an increased risk of poor anthropometric status.

[Aminothiols in blood plasma at different subtypes of ischemic stroke]. / Aminotioly plazmy krovi pri razlichnykh podtipakh ishemicheskogo insul'ta.

OBJECTIVE: To evaluate the hemostasis of plasma aminothiols in different subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 177 patients, aged 62 (55-68) years, admitted in the first 8-24 hours since IS onset. The pathogenetic subtype of IS was clarified according to the results of clinical and instrumental examination by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Determination of the total plasma aminothiols levels, their reduced forms and redox status was performed using the ultra-efficient Acquity H-Class UPLC liquid chromatograph (Waters, CSHA). RESULTS: Large-artery atherosclerosis was diagnosed in 24.3% patients, cardioembolic stroke in 20.3%, lacunar stroke in 55.4%. Significant differences in total levels of cysteine (Cys), glutathione (Gsh) and homocysteine (Hcy) were identified in patients with different IS subtypes. Patients with large-artery atherosclerosis and lacunar stroke showed the highest level of Hcy, patients with cardioembolic stroke had the lowest levels of Cys and Gsh. CONCLUSION: Total levels of plasma aminothiols are associated with different subtypes of IS.

Protein succination as a potential surrogate biomarker of airway obstruction. The ilervas project.

BACKGROUND: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. The latter can alter metabolite intermediates in the Krebs cycle leading to the formation of the cysteine-fumarate adduct S-(2-succino) cysteine (2SC) in proteins (protein succination). Protein succination has not been described in airways diseases. RESEARCH QUESTION: To assess differences in levels of AGEs and 2SC between patients with AO and normal spirometry. STUDY DESIGN: and Methods: In this case-control study, we investigated 35 moderate to severe AO patients and 31 subjects with normal spirometry, matched for age, gender, body mass index (BMI), tobacco history, prediabetes and adherence to Mediterranean diet. Plasma 2SC and AGEs concentrations were measured by GS/MS, and AGEs in skin were determined measuring autofluorescence (SAF). Multivariate logistic regression models explored the association between AGEs in the skin, 2SC and the presence of AO. RESULTS: The population was predominantly middle-age (mean of 58.7 years-old), overweight (median of BMI 26.7 kg/m2) and male subjects (69.7%). Patients with AO showed higher values of SAF (p = 0.04) and 2SC (p = 0.047). No differences were observed for plasma AGEs. SAF and 2SC were significantly associated with the presence of AO after adjusting for age, gender, smoking history, BMI and Mediterranean diet score (p = 0.041 and p = 0.038, respectively). INTERPRETATION: Skin AGEs and 2SC are increased in patients with moderate to severe AO and independently associated with its presence. Further studies should confirm these findings and explore their potential role as a biomarker for the disease.

Association of Maternal Plasma Total Cysteine and Growth among Infants in Nepal: A Cohort Study.

Cysteine is a semi-essential amino acid that has been positively associated with growth in children. However, transgenerational effects remain unclear. The aim of this analysis was to assess whether maternal plasma total cysteine (tCys) concentration is associated with various growth indicators in infants living in peri-urban settings in Bhaktapur, Nepal. We used data from the 561 mothers enrolled in an ongoing randomized controlled trial. We built linear regression models to evaluate the associations between maternal tCys and birth weight, length-for-age Z-scores (LAZ) and weight-for-length Z-scores (WLZ) at birth and six months of age. Maternal tCys was inversely associated with birth weight among boys after adjusting for confounders (p < 0.05). In addition, there was a negative association between maternal tCys and LAZ at birth (p < 0.01). No associations between maternal tCys and the other anthropometric indicators were found significant, although there was a tendency for maternal tCys to be associated positively with WLZ at birth among girls (p < 0.10). This is a first study evaluating transgenerational relation of tCys on growth in infants. Further, larger and more comprehensive studies are needed to determine if and how maternal tCys alters child growth.

High-sensitivity Detection of Cysteine and Glutathione Using Au Nanoclusters Based on Aggregation-induced Emission.

Gold nanoclusters (AuNCs) stabilized by glutathione (GSH) have been synthesized using a simple one-pot method, which were used as a fluorescence-enhanced probe for the detection of cysteine (Cys) and GSH. The detection is based on the finding that the weak yellow fluorescence of the AuNCs, with excitation/emission maxima of 430/600 nm, can be enhanced by Cys and GSH via NCs aggregation. This method is selective for Cys and GSH. According to the fluorescence enhancement, the detection ranges of AuNCs for Cys and GSH are 2.49 µM ~ 0.80 mM and 1.99 µM ~ 0.44 mM, with the detection limit of 0.42 µM and 0.27 µM, respectively. In addition, the probe has good anti-interference performance over other common biomolecules. Importantly, the probe is successfully used for the determination of Cys in human serum samples, displaying the potential application of the probe in the detection of biological sulfhydryl molecules in actual samples.