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Background & Objective: Polycystic ovary syndrome is the prevailing endocrine disorder in females and one of the main causes of anovulatory sterility. It is associated with symptoms, disturbs females of reproductive age and affects their quality of life. Cathepsins are proteases that perform a variety of physiological tasks, including activating the complement system, regulating the immune system, and regulating, tissue homeostasis, and ion channel functioning. There are various subtypes, including aspartic, cysteine, and serine cathepsins. Cat S belongs to the family of cysteine cathepsin proteases. A lysosomal protease can encourage the endo-lysosomal pathway's destruction of undesirable or damaged proteins. The present study was conducted with aim to investigate the relationship between cathepsin S and Insulin Resistance in Iraqi women with PCOS. Materials & Methods: An Observational Case-Control Study was performed. The levels of cathepsin S, Insulin, glucose, and insulin resistance were evaluated for 135 blood samples (90 patients and 45 controls). Cathepsin S and Fasting Insulin were estimated by sandwich ELISA method, while glucose was performed using the COBAS INTEGRA 400 plus analyzer. Insulin resistance was calculated by the HOMA-IR formula. All the test procedures were performed at the College of Medicine’s Research Unit /Al-Nahrain University/ Baghdad-Iraq. The study was conducted from December to the end of March of 2023. Results: The levels of cathepsin S, Insulin, HOMA-IR, and glucose were elevated among PCOS patients with a high significant difference (HS) (P<0.0001) between the patient and the control groups. Conclusion: According to the results of this study, Cat S has the potential to be a novel vital component among PCOS parameters. Insulin Resistance continues to rise among PCOS women leading to a necessity for studying its specific mechanism and its genetic origins. [ABSTRACT FROM AUTHOR]

In artificially controlled pot experiments, perennial ryegrass was mixed with other leguminous plants (white clover and alfalfa) and treated with lead, zinc and cadmium (337 mg·kg, 648 mg·kg, and 9 mg·kg, respectively) to simulate compound pollution conditions. The results showed that the concentrations of heavy metals, transport factors, and bioconcentration factors in mixed planting of ryegrass decreased compared with those in monoculture. Regardless of whether heavy metal pollution was introduced, mixed planting increased the aboveground and underground biomasses of ryegrass. The different mixed planting treatments had no significant impact on the chlorophyll concentration of ryegrass. The mowing time, mixed planting treatment, and heavy metal treatment had impacts on antioxidant and osmotic adjustment substances, and there were some interactions. The mixed planting treatment did not significantly affect glutathione concentration, cysteine concentration, or nonprotein thiol. Mixed planting generally increased the nitrogen and phosphorus concentrations of ryegrass while reducing the stoichiometric ratio of carbon, nitrogen, and phosphorus. These results suggest that the mixed planting of ryegrass with legumes promotes the growth of ryegrass in the presence of high concentrations of heavy metal pollution. However, it does not enhance the ability of ryegrass to remediate heavy metal pollution in the soil. [ABSTRACT FROM AUTHOR]

This article raises the relevancy problems of bimetallic nanostructures using to inhibit corrosion processes specific to various sulfur-containing media, including the extraction and transportation of natural hydrocarbons, in oil and gas condensate equipment. The environmental aspect of the research is the possibility of using bimetallic nanostructures modified with cysteine as environmentally friendly agents that protect steel from corrosion, especially in a thiol medium. There are presented experimental data on the synthesis and study of bimetallic nanostructures based on copper and silver in a thiol medium based on cysteine aminoacid. The research field is conditioned by these days' tendency that advanced developments in many branches of science are directly associated to the application of nanomaterials. The high action efficiency of these materials is achieved due to their highly dispersed state, distinguishing them favorably from conventional macroobjects. The synthesis of Cu/Ag nanostructures was carried out due to the unique properties of bimetals, such as increased activity of atoms in the surface layer, display of quantum effects, etc., that are more pronounced than those in monometallic nanostructures. The main article concept lies within simulation the process of sulfides and other sulfur compounds formation with bimetallic nanoparticles to protect oil and gas equipment from sulfur-containing corrosive agents in aqueous medium. The goal is to synthesize the copper-silver bimetallic microparticles stabilized with apple pectin and verification of the possibility of forming a metal-sulfur bond at the nanoscale level with cysteine aminoacid as a suitable and convenient compound. The objectives include directly the method of synthesis of the bimetallic microstructure Cu-Ag, stabilized with a solution of apple pectin; absorption spectrophotometry of the studied disperse system of bimetallic Cu-Ag microparticles in the visible region; scanning electron microscopy (SEM) of the bimetallic Cu-Ag microparticles obtained; study of chemisorption of L-cysteine hydrochloride on the dispersed phase surface of bimetallic Cu-Ag microparticles; Raman-scattering spectroscopy of the sample obtained after chemisorption. [ABSTRACT FROM AUTHOR]

Objectives: Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation. Methods: HMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC β-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation. Results: Degranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions. Conclusion: These findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases. [ABSTRACT FROM AUTHOR]

A digital image colorimetry method utilizing a smartphone as the detection tool was developed for the determination of acetylcysteine and cysteine in effervescent tablets. The method is based on a simple nitroprusside test specific for free −SH groups in aminothiols, which results in orange-red color sample solutions for colorimetric detection. The analytical response of the colorimetric detection decreased as the amino acid concentration increased. The data of the digital images taken were processed to RGB (red–green–blue) color scales using the Color Detector application. Today's technology allows faster and easier analysis with the use of easily accessible and portable smartphones in colorimetric detection systems. The developed method has good linearity in a linear working range of 5.0–25 mg/L (41.27–206.34 µM) and 4.94–47.30 mg/kg (30.27–289.85 µM) for cysteine and acetylcysteine, respectively. The limit of detection and quantification values for cysteine and acetylcysteine were calculated as 1.0 and 3.4 mg/L (8.25–28.06 µM) and 1.8 and 6.1 mg/kg (11.03–37.38 µM), respectively. The applicability and accuracy of the developed method were tested on drug samples. According to the results, this method has the potential to be used in the routine analysis and quality control of pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

BackgroundNitric oxide (NO) has been identified as a signaling molecule generated during β-adrenergic receptor stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca2+ release via S-nitrosylation of CaMKIIδ (Ca2+/calmodulin kinase II delta) is emerging. NO donors are routinely used clinically for their cardioprotective effects on the heart, but it is unknown how NO donors modulate the proarrhythmic CaMKII to alter cardiac arrhythmia incidence. We test the role of S-nitrosylation of CaMKIIδ at the Cysteine-273 inhibitory site and cysteine-290 activating site in cardiac Ca2+ handling and arrhythmogenesis before and during β-adrenergic receptor stimulation.MethodsWe measured Ca2+-handling in isolated cardiomyocytes from C57BL/6J wild-type (WT) mice and mice lacking CaMKIIδ expression (CaMKIIδ-KO) or with deletion of the S-nitrosylation site on CaMKIIδ at cysteine-273 or cysteine-290 (CaMKIIδ-C273S and -C290A knock-in mice). Cardiomyocytes were exposed to NO donors, S-nitrosoglutathione (GSNO; 150 μM), sodium nitroprusside (200 μM), and β-adrenergic agonist isoproterenol (100 nmol/L).ResultsBoth WT and CaMKIIδ-KO cardiomyocytes responded to isoproterenol with a full inotropic and lusitropic Ca2+ transient response as well as increased Ca2+ spark frequency. However, the increase in Ca2+ spark frequency was significantly attenuated in CaMKIIδ-KO cardiomyocytes. The protection from isoproterenol-induced Ca2+ sparks and waves was mimicked by GSNO pretreatment in WT cardiomyocytes but lost in CaMKIIδ-C273S cardiomyocytes. When GSNO was applied after isoproterenol, this protection was not observed in WT or CaMKIIδ-C273S but was apparent in CaMKIIδ-C290A. In Langendorff-perfused isolated hearts, GSNO pretreatment limited isoproterenol-induced arrhythmias in WT but not CaMKIIδ-C273S hearts, while GSNO exposure after isoproterenol sustained or exacerbated arrhythmic events.ConclusionsWe conclude that prior S-nitrosylation of CaMKIIδ at cysteine-273 can limit subsequent β-adrenergic receptor-induced arrhythmias, but that S-nitrosylation at cysteine-290 might worsen or sustain β-adrenergic receptor-induced arrhythmias. This has important implications for the administration of NO donors in the clinical setting.

While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multiomics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Among oncologic ROS, H2O2 specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine γ-lyase (CTH), which converts cystathionine to the nonessential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.

Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse human proteins. Determining which of these covalent binding events affect protein function, however, remains challenging. Here we describe a base-editing strategy to infer the functionality of cysteines by quantifying the impact of their missense mutation on cancer cell proliferation. The resulting atlas, which covers more than 13,800 cysteines on more than 1,750 cancer dependency proteins, confirms the essentiality of cysteines targeted by covalent drugs and, when integrated with chemical proteomic data, identifies essential, ligandable cysteines in more than 160 cancer dependency proteins. We further show that a stereoselective and site-specific ligand targeting an essential cysteine in TOE1 inhibits the nuclease activity of this protein through an apparent allosteric mechanism. Our findings thus describe a versatile method and valuable resource to prioritize the pursuit of small-molecule probes with high function-perturbing potential.

This article raises the relevancy problems of bimetallic nanostructures using to inhibit corrosion processes specific to various sulfur-containing media, including the extraction and transporta-tion of natural hydrocarbons, in oil and gas condensate equipment. The environmental aspect of the research is the possibility of using bimetallic nanostructures modified with cysteine as environmentally friendly agents that protect steel from corrosion, especially in a thiol medium. There are presented experimental data on the synthesis and study of bimetallic nanostructures based on copper and silver in a thiol medium based on cysteine aminoacid. The research field is conditioned by these days’ tendency that advanced developments in many branches of sci-ence are directly associated to the application of nanomaterials. The high action efficiency of these materials is achieved due to their highly dispersed state, distinguishing them favorably from conventional macroobjects. The synthesis of Cu/Ag nanostructures was carried out due to the unique properties of bimetals, such as increased activity of atoms in the surface layer, display of quantum effects, etc., that are more pronounced than those in monometallic nanostructures. The main article concept lies within simulation the process of sulfides and oth-er sulfur compounds formation with bimetallic nanoparticles to protect oil and gas equipment from sulfur-containing corrosive agents in aqueous medium. The goal is to synthesize the cop-per-silver bimetallic microparticles stabilized with apple pectin and verification of the possibil-ity of forming a metal-sulfur bond at the nanoscale level with cysteine aminoacid as a suitable and convenient compound. The objectives include directly the method of synthesis of the bi-metallic microstructure Cu-Ag, stabilized with a solution of apple pectin; absorption spectro-photometry of the studied disperse system of bimetallic Cu-Ag microparticles in the visible region; scanning electron microscopy (SEM) of the bimetallic Cu-Ag microparticles obtained; study of chemisorption of L-cysteine hydrochloride on the dispersed phase surface of bimetal-lic Cu-Ag microparticles; Raman-scattering spectroscopy of the sample obtained after chemi-sorption.

BackgroundThe higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood.MethodsWe performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately.ResultsSixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways.ConclusionsAdduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males.ImpactOnly two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.

Uterine artery (UA) hydrogen sulfide (H2S) production is augmented in pregnancy and, on stimulation by systemic/local vasodilators, contributes to pregnancy-dependent uterine vasodilation; however, how H2S exploits this role is largely unknown. S-sulfhydration converts free thiols to persulfides at reactive cysteine(s) on targeted proteins to affect the entire proteome posttranslationally, representing the main route for H2S to elicit its function. Here, we used Tag-Switch to quantify changes in sulfhydrated (SSH-) proteins (ie, sulfhydrome) in H2S-treated nonpregnant and pregnant human UA. We further used the low-pH quantitative thiol reactivity profiling platform by which paired sulfhydromes were subjected to liquid chromatography tandem mass spectrometry-based peptide sequencing to generate site (cysteine)-specific pregnancy-dependent H2S-responsive human UA sulfhydrome. Total levels of sulfhydrated proteins were significantly greater in pregnant vs nonpregnant human UA and further stimulated by treatment with sodium hydrosulfide. We identified a total of 360 and 1671 SSH-peptides from 480 and 1186 SSH-proteins in untreated and sodium hydrosulfide-treated human UA, respectively. Bioinformatics analyses identified pregnancy-dependent H2S-responsive human UA SSH peptides/proteins, which were categorized to various molecular functions, pathways, and biological processes, especially vascular smooth muscle contraction/relaxation. Pregnancy-dependent changes in these proteins were rectified by immunoblotting of the Tag-Switch labeled SSH proteins. Low-pH quantitative thiol reactivity profiling failed to identify low abundance SSH proteins such as KATP channels in human UA; however, immunoblotting of Tag-Switch-labeled SSH proteins identified pregnancy-dependent upregulation of SSH-KATP channels without altering their total proteins. Thus, comprehensive analyses of human UA sulfhydromes influenced by endogenous and exogenous H2S inform novel roles of protein sulfhydration in uterine hemodynamics regulation.

The tomato Tm-22 gene was considered to be one of the most durable resistance genes in agriculture, protecting against viruses of the Tobamovirus genus, such as tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV). However, an emerging tobamovirus, tomato brown rugose fruit virus (ToBRFV), has overcome Tm-22 , damaging tomato production worldwide. Tm-22 encodes a nucleotide-binding leucine-rich repeat (NLR) class immune receptor that recognizes its effector, the tobamovirus movement protein (MP). Previously, we found that ToBRFV MP (MPToBRFV ) enabled the virus to overcome Tm-22 -mediated resistance. Yet, it was unknown how Tm-22 remained durable against other tobamoviruses, such as TMV and ToMV, for over 60 years. Here, we show that a conserved cysteine (C68) in the MP of TMV (MPTMV ) plays a dual role in Tm-22 activation and viral movement. Substitution of MPToBRFV amino acid H67 with the corresponding amino acid in MPTMV (C68) activated Tm-22 -mediated resistance. However, replacement of C68 in TMV and ToMV disabled the infectivity of both viruses. Phylogenetic and structural prediction analysis revealed that C68 is conserved among all Solanaceae-infecting tobamoviruses except ToBRFV and localizes to a predicted jelly-roll fold common to various MPs. Cell-to-cell and subcellular movement analysis showed that C68 is required for the movement of TMV by regulating the MP interaction with the endoplasmic reticulum and targeting it to plasmodesmata. The dual role of C68 in viral movement and Tm-22 immune activation could explain how TMV was unable to overcome this resistance for such a long period.

The biological and pathological functions of cathepsin B occur in acidic lysosomes and at the neutral pH of cytosol, nuclei, and extracellular locations. Importantly, cathepsin B displays different substrate cleavage properties at acidic pH compared to neutral pH conditions. It is, therefore, desirable to develop specific substrates for cathepsin B that measure its activity over broad pH ranges. Current substrates used to monitor cathepsin B activity consist of Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, but they lack specificity since they are cleaved by other cysteine cathepsins. Furthermore, Z-Arg-Arg-AMC monitors cathepsin B activity at neutral pH and displays minimal activity at acidic pH. Therefore, the purpose of this study was to design and validate specific fluorogenic peptide substrates that can monitor cathepsin B activity over a broad pH range from acidic to neutral pH conditions. In-depth cleavage properties of cathepsin B were compared to those of the cysteine cathepsins K, L, S, V, and X via multiplex substrate profiling by mass spectrometry at pH 4.6 and pH 7.2. Analysis of the cleavage preferences predicted the tripeptide Z-Nle-Lys-Arg-AMC as a preferred substrate for cathepsin B. Significantly, Z-Nle-Lys-Arg-AMC displayed the advantageous properties of measuring high cathepsin B specific activity over acidic to neutral pHs and was specifically cleaved by cathepsin B over the other cysteine cathepsins. Z-Nle-Lys-Arg-AMC specifically monitored cathepsin B activity in neuronal and glial cells which were consistent with relative abundances of cathepsin B protein. These findings validate Z-Nle-Lys-Arg-AMC as a novel substrate that specifically monitors cathepsin B activity over a broad pH range.

Herbicides in the widely used chloroacetanilide class harbor a potent electrophilic moiety, which can damage proteins through nucleophilic substitution. In general, damaged proteins are subject to misfolding. Accumulation of misfolded proteins compromises cellular integrity by disrupting cellular proteostasis networks, which can further destabilize the cellular proteome. While direct conjugation targets can be discovered through affinity-based protein profiling, there are few approaches to probe how cellular exposure to toxicants impacts the stability of the proteome. We apply a quantitative proteomics methodology to identify chloroacetanilide-destabilized proteins in HEK293T cells based on their binding to the H31Q mutant of the human Hsp40 chaperone DNAJB8. We find that a brief cellular exposure to the chloroacetanilides acetochlor, alachlor, and propachlor induces misfolding of dozens of cellular proteins. These herbicides feature distinct but overlapping profiles of protein destabilization, highly concentrated in proteins with reactive cysteine residues. Consistent with the recent literature from the pharmacology field, reactivity is driven by neither inherent nucleophilic nor electrophilic reactivity but is idiosyncratic. We discover that propachlor induces a general increase in protein aggregation and selectively targets GAPDH and PARK7, leading to a decrease in their cellular activities. Hsp40 affinity profiling identifies a majority of propachlor targets identified by competitive activity-based protein profiling (ABPP), but ABPP can only identify about 10% of protein targets identified by Hsp40 affinity profiling. GAPDH is primarily modified by the direct conjugation of propachlor at a catalytic cysteine residue, leading to global destabilization of the protein. The Hsp40 affinity strategy is an effective technique to profile cellular proteins that are destabilized by cellular toxin exposure. Raw proteomics data is available through the PRIDE Archive at PXD030635.

Growth of Chlamydomonas reinhardtii in zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding "first responder" proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine, and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ∼80-fold, corresponding to ∼2.8 × 109 molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is an in vivo Cu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.

Proteinaceous cysteines function as essential sensors of cellular redox state. Consequently, defining the cysteine redoxome is a key challenge for functional proteomic studies. While proteome-wide inventories of cysteine oxidation state are readily achieved using established, widely adopted proteomic methods such as OxICAT, Biotin Switch, and SP3-Rox, these methods typically assay bulk proteomes and therefore fail to capture protein localization-dependent oxidative modifications. Here we establish the local cysteine capture (Cys-LoC) and local cysteine oxidation (Cys-LOx) methods, which together yield compartment-specific cysteine capture and quantitation of cysteine oxidation state. Benchmarking of the Cys-LoC method across a panel of subcellular compartments revealed more than 3,500 cysteines not previously captured by whole-cell proteomic analysis. Application of the Cys-LOx method to LPS-stimulated immortalized murine bone marrow-derived macrophages (iBMDM), revealed previously unidentified, mitochondrially localized cysteine oxidative modifications upon pro-inflammatory activation, including those associated with oxidative mitochondrial metabolism.

Abstract Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γmax, γCMC, and Amin, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells.

In spite of 150 years of studying malaria, the unique features of the malarial parasite, Plasmodium, still perplex researchers. One of the methods by which the parasite manages its gene expression is epigenetic regulation, the champion of which is PfGCN5, an essential enzyme responsible for acetylating histone proteins. PfGCN5 is a ∼170 kDa chromatin‐remodeling enzyme that harbors the conserved bromodomain and acetyltransferase domain situated in its C‐terminus domain. Although the PfGCN5 proteolytic processing is essential for its activity, the specific protease involved in this process still remains elusive. Identification of PfGCN5 interacting proteins through immunoprecipitation (IP) followed by LC‐tandem mass spectrometry analysis revealed the presence of food vacuolar proteins, such as the cysteine protease Falcipain 3 (FP3), in addition to the typical members of the PfGCN5 complex. The direct interaction between FP3 and PfGCN5 was further validated by in vitro pull‐down assay as well as IP assay. Subsequently, use of cysteine protease inhibitor E64d led to the inhibition of protease‐specific processing of PfGCN5 with concomitant enrichment and co‐localization of PfGCN5 and FP3 around the food vacuole as evidenced by confocal microscopy as well as electron microscopy. Remarkably, the proteolytic cleavage of the nuclear protein PfGCN5 by food vacuolar protease FP3 is exceptional and atypical in eukaryotic organisms. Targeting the proteolytic processing of GCN5 and the associated protease FP3 could provide a novel approach for drug development aimed at addressing the growing resistance of parasites to current antimalarial drugs. [ABSTRACT FROM AUTHOR]

To study the effects of pre-and post-processing on total protein, amino acid composition, and nutritional value of Polygonatum, and to clarify the nutritional basis of its edible nutritional value and therapeutic effect. The protein amino acid composition of Polygonatum and processed products were analyzed, and the differences in amino acid composition in the samples were analyzed by principal component analysis (PCA), hierarchical cluster analysis (HCA), and t-test, and the protein nutrition of Polygonatum and processed products were evaluated according to the amino acid reference model of Food and Agriculture Organization of the United Nations / World Health Organization. Results showed that there were 17 kinds of amino acids in Polygonatum before and after processing, and the content of umami amino acids (glutamic acid and aspartic acid) was the highest, and it was rich in medicinal amino acids, essential amino acids, branched-chain amino acids, and so on. More medicinal amino acids and umami amino acids revealed the reasons why Polygonatum, as a traditional medicinal and edible material, could improve the physical functions and make the dishes more delicious. The results of PCA and HCA showed that the roots were divided into two types, including the processed group and the non-processed group, which indicated that processing played an important role in the changes in the amino acid composition of Polygonatum protein. Compared with the non-processed group, serine, cysteine, lysine and arginine were significantly lower, while methionine, isoleucine, valine, leucine, threonine, phenylalanine, proline, and glycine were significantly higher. There was no significant difference in functional amino acids between processed and non-processed groups, and essential amino acids showed a significant increase, all of the results indicated that processing could help not only to keep its work on healthcare but also to improve its nutritional value. In processed and non-processed Polygonatum roots, respectively, the first limited amino acids were lysine and isoleucine. The priority order on protein nutritional value was processed roots > raw roots according to protein nutrition evaluation results. Thus, processing is beneficial to improve the nutritional value and quality of Polygonatum. [ABSTRACT FROM AUTHOR]

Aqueous soft matter, including supramolecular hydrogels capable of exhibiting stimuli–responsive macroscopic phase transitions, has attracted increasing attention for the exploration of functional soft materials. However, the investigation of supramolecular hydrogels that undergo autonomous and multiple macroscopic phase transitions (e.g., gel–sol–gel, sol–gel–sol) in response to the surrounding environment without repeated additions of stimuli has remained largely unexplored. In this study, the oxidation‐responsive autonomous gel–sol–gel transitions of supramolecular hydrogels fabricated via the self‐assembly of a simple fluorenylmethyloxycarbonyl (Fmoc)‐protected, benzylated cysteine (Fmoc‐CBzl) is presented. During the evaluation of the oxidation process of Fmoc‐CBzl, it is revealed that the oxidized products, two diastereomeric sulfoxides (Fmoc‐CBzl‐(R)‐O and Fmoc‐CBzl‐(S)‐O), exhibit significantly different self‐assembly propensities under aqueous conditions. It may be noteworthy that the chirality of sulfoxide is largely overlooked and not effectively used to modulate supramolecular, self‐assembled nanostructures. The difference in the self‐assembly propensities and kinetics of self‐assembly/disassembly as well as co‐assembly will contribute to oxidation‐responsive autonomous gel–sol–gel transitions. [ABSTRACT FROM AUTHOR]

Real-time, in situ, and visual characterization of non-equilibrium self-assembly processes is of great interest because of its importance, but it is challenging because of its complexity. Herein, we construct an adduct of vibration-induced emission (VIE)-active N,N′-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC) and a cysteine derivative, i.e., di-tert-butyl 3,3′-disulfanediylbis(2-formamidopropanoate) (CystBu), where DPAC functions as both a hydrophobic motif and fluorescent reporter while CystBu acts as a hydrophilic group and hydrogen-bonding moiety. The resulting adduct DPAC-CystBu-DPAC is capable of self-assembly and gradually transforming from a non-equilibrium non-dissipative metastable state to a thermodynamically stable state over time. By virtue of the conformation-dependent emission feature of the VIE fluorogen, the whole self-assembly process can be self-monitored by the continuous fluorescence changes from orange-red to blue, in an in situ, real-time, and visual fashion. Moreover, benefiting from the chirality of CystBu and the conformation-flexibility of DPAC, circularly polarized luminescence (CPL) with an asymmetry factor (glum) of up to 7.1 × 10−2 is induced as the kinetically-captured aggregates are transformed into columnar assemblies in a thermodynamically stable state. This work not only opens a new avenue for the real-time and in situ characterization of the self-assembly processes, helping to pave the way for the preparation of complex out-of-equilibrium supramolecular functional systems, but also provides a new type of CPL material. [ABSTRACT FROM AUTHOR]

A green strategy for the selective alkylation of cysteine-containing peptides in a continuous flow reactor has been developed, providing an efficient pathway to alkylated cysteine-containing peptides under mild conditions. This process does not need light, metal catalysts, or oxidative reagents. It provides a useful method for the modification of amino acids and peptides. As one of the low cost and synthetic versatile raw materials, the alkyl thianthenium salt can be used as an alkylation source in the preparation of alkylated cysteine-containing peptides. In addition, the microfluidics technology can shorten the reaction time and improve the efficiency, thus reducing the costs and energy consumption of the synthesis process. A series of alkylated cysteine-containing peptides (41 examples) has been synthesized here with a short residence time (14.0 min), and with good to excellent yields. [ABSTRACT FROM AUTHOR]

The article discusses the cyanopyridine-aminthiol click reaction, a bioconjugation method that allows for precise and selective chemical modifications in complex biological systems. The reaction is efficient, exhibits excellent chemoselectivity, and is stable under mild redox conditions. It is orthogonal to most endogenous reactants, except for cysteine itself and peptides or proteins with N-terminal cysteine residues. The reaction has been used for peptide macrocyclization, the synthesis of macrocyclic peptides, and the creation of DNA-encoded libraries. Future research is needed to explore its potential for broader bioconjugation purposes. [Extracted from the article]

Luminescent cyclometallated iridium(III) complexes bearing a 2-formylphenylboronic acid moiety were designed; one of the complexes was utilised to modify peptides containing an N-terminal cysteine to afford luminescent conjugates with selective organelle-targeting or furin-responsive properties. [ABSTRACT FROM AUTHOR]

Simple Summary: Methionine (Met) and cysteine (Cys) are usually performance-limiting amino acids in broiler feed. To balance diets in order to meet birds' requirements, DL-Methionine (DL-Met) or the hydroxy analogue of methionine (MHA), which is a precursor of methionine, are common supplements. Based on a multitude of simultaneous dose–response trials, a 65% bioefficacy is recommended for MHA relative to DL-Met. This recommendation has often been tested under various experimental conditions. The present meta-analysis of effect sizes from 95 data sets revealed very little heterogeneity of data combined with the small effect sizes of DL-Met treatments when DL-Met replaced MHA at a weight ratio of 65:100. The effect sizes of DL-Met treatments were not different from MHA treatments, which confirms that 100 units of an MHA product can be replaced by 65 units of DL-Met without compromising performance. The data analysis also revealed that this result was not affected by the broiler strain, the diet type, or the MHA product type being used in the feeding experiments. Moreover, the broiler feeding trials supposed to challenge the 65% bioefficacy recommendation were successful at any dietary Met+Cys supply, including the most sensitive test conditions at marginal Met+Cys supply. While the supplementation of methionine (Met) sources in broiler feeds has been established for several decades, there is debate on the nutritional value of the methionine hydroxy analogue of methionine (MHA) relative to DL-Met. Based on a recommendation suggesting that MHA is 65% as effective as DL-Met, many feeding trials have been conducted to challenge this recommendation. A literature search found 25 publications contributing 95 data sets suitable to compute Hedges' g effect sizes used in the meta-analysis. The data had very little heterogeneity of almost zero and the small effect sizes of the DL-Met results were not significantly different from MHA. Data were split in various subgroups, finally suggesting that neither broiler strain (Cobb 500, Ross 308), diet type (corn, wheat based), origin of data (peer-reviewed, grey literature), nor MHA product (MHA-free acid, MHA-calcium salt) impacted the outcome of the meta-analysis. Moreover, distinguishing data in groups with dietary Met+Cysteine (Cys) levels below, at, or above requirement demonstrated that there was no interaction with general Met+Cys supply. It is therefore concluded that MHA products can be replaced by DL-Met in a weight-to-weight ratio of 100:65 in any production condition without compromising broiler performance [ABSTRACT FROM AUTHOR]

A sensitive and interference-free method based on hydride generation high-resolution continuum source quartz tube atomic absorption spectrometry in dilute HCl was developed for total and inorganic As (tAs, iAs) determination in soil, sediments, and sludge. Sample preparation involved microwave-assisted digestion in aqua regia for tAs and extraction in 10 mol L−1 HCl for iAs. In both cases, the prereduction of As(V) to As(III) was carried out with L-cysteine, while derivatization to arsine with 0.6% NaBH4 was performed in the presence of 0.2% L-cysteine in 0.01 mol L−1 HCl (pH 2.00 ± 0.01). Inorganic arsenic determination was validated with 87 ± 7% extraction efficiency. The recovery of tAs in certified reference materials was 98 ± 23%, while the value for iAs in spiked samples was 95 ± 10%. The method was selective for iAs determination and did not require separation of iAs by liquid-liquid extraction in an organic solvent. The results were verified using the Tukeyʼs multiple comparison test for p > 0.05 (experimental values 0.063 to 0.999). The method is greatly simplified due to no requirement for the separation of iAs species, absence of spectral interference, similar derivatization conditions for tAs/iAs, and possibility of using external calibration. The limits of detection for tAs and iAs were 0.006 mg kg−1. Concentrations of 0.37–545 mg kg−1 tAs and 0.33–280 mg kg−1 iAs in real samples were determined with precisions from 3.7 to 12.2% and 6.8 to 15.0%. [ABSTRACT FROM AUTHOR]

Synapse maintenance is essential for generating functional circuitry, and decrement in this process is a hallmark of neurodegenerative disease. Yet, little is known about synapse maintenance in vivo. Cysteine string protein a (CSPa), encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is necessary for synapse maintenance and linked to neurodegeneration. To investigate the transcriptional changes associated with synapse maintenance, we performed single-nucleus transcriptomics on the cortex of young CSPa knockout (KO) mice and littermate controls. Through differential expression and gene ontology analysis, we observed that both neurons and glial cells exhibit unique signatures in the CSPa KO brain. Significantly, all neuronal classes in CSPa KO brains show strong signatures of repression in synaptic pathways, while up-regulating autophagy-related genes. Through visualization of synapses and autophagosomes by electron microscopy, we confirmed these alterations especially in inhibitory synapses. Glial responses varied by cell type, with microglia exhibiting activation. By imputing cell-cell interactions, we found that neuron-glia interactions were specifically increased in CSPa KO mice. This was mediated by synaptogenic adhesion molecules, with the classical Neurexin1-Neuroligin 1 pair being the most prominent, suggesting that communication of glial cells with neurons is strengthened in CSPa KO mice to preserve synapse maintenance. Together, this study provides a rich dataset of transcriptional changes in the CSPa KO cortex and reveals insights into synapse maintenance and neurodegeneration. [ABSTRACT FROM AUTHOR]

Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γmax, γCMC, and Amin, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells. [ABSTRACT FROM AUTHOR]

The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as a first step in their disruption process. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i. e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as an oxidizing agent due to its biological role as a metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate‐κS and the trends for the different substrates were rationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic Density Functional Theory (DFT) calculations at ZORA‐M06/TZ2P ae // ZORA‐BLYP‐D3(BJ)/TZ2P. CCCC is oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate‐κO was attempted to assess whether this step may affect the ligand dissociation; however, it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as a trigger for ligand dissociation, possibly leading to metal ejection; molecular docking simulations also support this hypothesis. [ABSTRACT FROM AUTHOR]

Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown. [ABSTRACT FROM AUTHOR]

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research. [ABSTRACT FROM AUTHOR]

Short peptide sequences consisting of two cysteine residues separated by three other amino acids display complete change from random coil to α‐helical secondary structure in response to addition of Ag+ ions. The folded CXXXC/Ag+ complex involves formation of multinuclear Ag+ species and is stable in a wide pH range from below 3 to above 8. The complex is stable through reversed‐phase HPLC separation as well as towards a physiological level of chloride ions, based on far‐UV circular dichroism spectroscopy. In electrospray MS under acidic conditions a peptide dimer with four Ag+ ions bound was observed, and modelling based on potentiometric experiments supported this to be the dominating complex at neutral pH together with a peptide dimer with 3 Ag+ and one proton at lower pH. The complex was demonstrated to work as a N‐terminal nucleation site for inducing α‐helicity into longer peptides. This type of silver‐mediated peptide assembly and folding may be of more general use for stabilizing not only peptide folding but also for controlling oligomerization even under acidic conditions. [ABSTRACT FROM AUTHOR]

N -Methylisothiazolinone (MIT) is a thiol group modifier and antimicrobial agent. Arthrobacter sarcosine oxidase (SoxA), a diagnostic enzyme for assaying creatinine, loses its activity upon the addition of MIT, and its inactivation mechanism remains unclear. In this study, SoxA was chemically modified using MIT (mo-SoxA), and its structural and chemical properties were characterized. Spectral analysis data, oxygen consumption rates, and reactions were compared between intact SoxA and mo-SoxA. These demonstrate that the oxidative half-reaction toward oxygen is inhibited by MIT modification. The oxidase activity of mo-SoxA was approximately 2.1% of that of intact SoxA, and its dehydrogenase activity was approximately 4.2 times higher. The C-to-S mutants revealed that cooperative modification of 2 specific cysteine residues caused a drastic change in the enzyme reaction mode. Based on the modeled tertiary structures, the putative entrance for oxygen uptake is predicted to be blocked by the chemical modification of the 2 cysteine residues. [ABSTRACT FROM AUTHOR]

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan–cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system. [ABSTRACT FROM AUTHOR]

The carboxyl‐terminal (C‐terminal) S‐[(Z)‐2‐aminovinyl]‐cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post‐translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD‐like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species. The collaborative actions of LanD‐like proteins with diverse enzymes involved in dehydration, dethiolation or cyclization lead to the construction of structurally distinct peptide natural products with analogous C‐terminal macrocyclic moieties. This concept summarizes existing knowledge regarding biosynthetic pathways of AviCys analogs to emphasize the diversity of biosynthetic mechanisms that paves the way for future genome mining explorations into diverse peptide natural products. [ABSTRACT FROM AUTHOR]

Zinc anodes in aqueous batteries face challenges such as dendrite growth and interfacial instability. This study investigates the use of cysteine as an electrolyte additive to address these issues. By establishing the correlation between the size of zinc nuclei and the surface tensions/contact angle at the electrolyte‐anode interface, it is demonstrated that the addition of cysteine in the electrolyte alters the surface tensions/contact angle at the electrolyte‐anode interface and the nucleation process of zinc. This alteration results in the formation of smaller and more dispersed nuclei, as opposed to the formation of larger island grains. This has a profound impact on the subsequent deposition growth process, enabling smooth and uniform zinc electrodeposition without the formation of dendrites. Additionally, cysteine molecules create a stable interface during zinc plating and stripping, effectively preventing corrosion from side reactions. The incorporation of cysteine in the electrolyte significantly enhances cycling stability and extends the lifespan of zinc anodes in aqueous batteries. [ABSTRACT FROM AUTHOR]

Soybean meal is the main protein source for animal feed, but it has low content of the essential amino acids cysteine (Cys) and methionine (Met). In this research, an exotic germplasm (PI 399000) was crossed with 'Woodruff' to develop an F5‐derived recombinant inbred line (RIL) population for mapping quantitative trait loci for seed composition. The population was grown in six environments, and protein, oil, Cys, and Met were determined with near‐infrared spectroscopy. RILs were genotyped with the SoySNP6K BeadChip, and 1865 SNPs were used for analysis. QTL analysis identified three loci on chromosomes (Chrs) 6, 15 and 17 in at least five environments for protein; two QTLs on Chrs 14 and 17 in all environments for oil; three QTLs on Chrs 3, 6 and 10 for Cys and Met in at least three environments; and two QTLs for seed size on Chrs 17 and 20 in all environments. Stacking of protein and Cys + Met QTLs can increase both traits simultaneously, and 13 breeding lines were identified with improved seed composition. The markers linked to the QTLs can be used to assist the development of cultivars with improved meal quality. [ABSTRACT FROM AUTHOR]

Camellia oleifera is a native woody oil plant in southern China and is infected with anthracnose wherever it is grown. We previously identified Colletotrichum fructicola as the major causal agent of anthracnose on C. oleifera and found that CfAtg8 regulates the pathogenicity and development of C. fructicola. Here, we revealed that CfAtg4 interacts with CfAtg8, contributing to the formation of autophagosomes. The CfAtg81–160 allele, which only contains 1–160 amino acids of the CfAtg8, partially recovered the autophagosome numbers and autophagy defects of the ΔCfatg4 mutant. Consequently, these recoveries resulted in the restoration of the defects of the ΔCfatg4 mutant in growth and responses to different external stresses, albeit to an extent. Importantly, we illustrated the critical roles of CfAtg81–160 in appressoria formation, and pathogenicity. Collectively, our findings provide new insights into the importance of the interaction between CfAtg8 and CfAtg4 in the growth, autophagy and pathogenicity of the phytopathogenic fungi. [ABSTRACT FROM AUTHOR]

l -cysteine, a primary building block of mycothiol, plays an essential role in the defense mechanism of Mycobacterium tuberculosis (Mtb). However, it is unclear how Mtb regulates cysteine biosynthesis as no study has reported the cysteine regulatory complex (CRC) in Mtb. Serine acetyltransferase (SAT) and cysteine synthase (CS) interact to form CRC. Although Mt CS has been characterized well, minimal information is available on Mt SAT, which synthesizes, O-acetylserine (OAS), the precursor of cysteine. This study fills the gap and provides experimental evidence for the presence of Mt CRC and a non-canonical multi-oligomeric Mt SAT. We employed multiple analytical methods to characterize the oligomeric and kinetic properties of Mt SAT and Mt CRC. Results show that Mt SAT, lacking >75 N-terminal amino acids exists in three different assembly states; trimer, hexamer, and dodecamer, compared to the single hexameric state of SAT of other bacteria. While hexamers display the highest catalytic turnover, the trimer is the least active. The predominance of trimers at low physiologically relevant concentrations suggests that Mt SAT displays the lowest catalytic potential known. Further, the catalytic potential of Mt SAT is also significantly reduced in CRC state, in contrast to enhanced activity of SAT in CRC of other organisms. Our study provides insights into multi-oligomeric Mt SAT with reduced catalytic potential and demonstrates that both Mt SAT and Mt CS of Mycobacterium interact to form CRC, although with altered catalytic properties. We discuss our results in light of the altered biochemistry of the last step of canonical sulfate-dependent cysteine biosynthesis of Mycobacterium. [Display omitted] • Serine acetyltransferase from Mycobacterium tuberculosis (Mt SAT) lacks four N-terminal helices. • Mt SAT exists in three states, with the trimer demonstrating the least catalytic efficiency. • Only hexamers can form cysteine regulatory complex (CRC) with cysteine synthase, not trimers. • Together, results indicate that compromised catalytic efficiency of Mt SAT may be an evolutionary adaptation. [ABSTRACT FROM AUTHOR]

Reactive carbonyl species such as methylglyoxal (MGO) act as potent glycating agents that are implicated in several oxidative stress-induced diseases, including, but not limited to, cancer, diabetes and neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. In the present study, a combined approach of initial computational studies and in vitro analysis was utilized to investigate the therapeutic benefit of L-cysteine (CYS), a thiol-containing compound. Based on the reactive analysis using global and local density functional theory (DFT) descriptors, the data reported here has revealed that CYS matches its electron-donating capacity with the electron acceptor, methylglyoxal, making the former a good candidate sequestering agent for the latter. Furthermore, in vitro analysis shows that CYS exhibits significant inhibitory effects towards damaging protein structural alteration and formation of advanced glycation end products (AGEs). Such assessment came about through Congo red binding Assay and Antiglycation Assay using BSA-MGO and BSA-glucose model systems. Additionally, CYS also demonstrates a significant protective effect towards MGO-induced oxidative stress in mouse C2C12 myotubes. Therefore, this thiol-containing compound is a promising therapeutic tool for several glycation or AGEs-induced pathological conditions. The use of more relevant cellular and animal models of desired disease studies is recommended to better understand the mechanistic basis of CYS's potential therapeutic effect. This study utilizing the combined approach of computational and in-vitro analysis, provides helpful data to maximize the potential impact of CYS by designing related molecules that could serve as novel treatment strategies that are effective, safe, and accessible to all in the future. [ABSTRACT FROM AUTHOR]

Background: A large class of proteolytic enzymes known as cysteine cathepsins are created as pro-enzymes and are activated in slightly acidic conditions. They are crucial for both healthy cellular function and illness. Cysteine cathepsins are a family of proteases that play important roles in a variety of cellular processes, including protein turnover, cell adhesion, and migration. Main body: In breast cancer, cysteine cathepsins have been shown to be overexpressed in tumor cells and to be associated with poor prognosis. This review article discusses the role of cysteine cathepsins in breast cancer, focusing on their diagnostic potential. The article provides an overview of cysteine cathepsins, including their structure, function, and regulation in addition to the evidence for the overexpression of cysteine cathepsins in breast cancer and their association with a poor prognosis. Conclusions: The current review demonstrates the potential use of cysteine cathepsins as biomarkers for early detection and diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

This study presents a novel approach to modifying copolymers with active azide end-groups through click chemistry, specifically targeting the incorporation of cysteine amino acid. The synthesis commenced with the reaction between cysteine amino acid and propargyl amine, yielding the alkyne-terminated amino acid Boc-Cys(Bnz)-PA compound. Through the click chemistry methodology, the copolymer with active azide ends was modified with alkyne-terminated Cys-PA. Thermal characterization of the copolymers was performed via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). DSC measurements revealed an increase in glass transition temperature (Tg) from 65 °C to 83 °C upon the modification with cysteine, indicating enhanced thermal stability. However, TGA data suggested a decrease in thermal stability as evidenced by lower initial degradation temperatures for the modified copolymer compared to the unmodified counterpart.The degradation activation energies of the copolymers were estimated using the Flynn-Wall-Ozawa method across various conversion ranges, demonstrating higher thermal degradation activation energy for the modified copolymer compared to the unmodified one. Dielectric behavior analysis conducted at room temperature over a frequency range from 100 Hz to 20 kHz revealed a decreasing trend in dielectric constant and dielectric loss values with increasing frequency for all copolymer structures. The alternating current (AC) conductivities at 30 kHz were calculated as 1.84 × 10−7 S cm−1, and 4.75 × 10−7 S cm−1 for P(VBCl-co-VBN3 0.77) and (P(VBCl-co-(VBN3-click-Cys)0.77), respectively, indicating a frequency-dependent conductivity enhancement with increasing frequency. Overall, the results suggest that these polymeric materials, containing amino acid structures, hold promise as dielectric materials for low-frequency and low-voltage devices such as sensors, owing to their tunable thermal and dielectric properties achieved through click chemistry modification. [ABSTRACT FROM AUTHOR]

In the system L-cysteine-H3PO3–H2O, a new salt with a dimeric cation, (L-CysH⋯L-Cys)(H2PO3), has been obtained. The compound exhibits incongruent solubility and is synthesized using an equimolar ratio of L-cysteine and phosphorous acid. It crystallizes in the orthorhombic space group P212121. The dimeric (L-CysH⋯L-Cys) cation is formed due to a strong O–H⋯O hydrogen bond with an O⋯O distance of 2.498(2) Å. Phosphite anions in the structure are linked to infinite chains. An IR spectrum is recorded and discussed based on its structure. [ABSTRACT FROM AUTHOR]

SUMMARY: Glutathione (GSH) is required for various physiological processes in plants, including redox regulation and detoxification of harmful compounds. GSH also functions as a repository for assimilated sulfur and is actively catabolized in plants. In Arabidopsis, GSH is mainly degraded initially by cytosolic enzymes, γ‐glutamyl cyclotransferase, and γ‐glutamyl peptidase, which release cysteinylglycine (Cys‐Gly). However, the subsequent enzyme responsible for catabolizing this dipeptide has not been identified to date. In the present study, we identified At4g17830 as a Cys‐Gly dipeptidase, namely cysteinylglycine peptidase 1 (CGP1). CGP1 complemented the phenotype of the yeast mutant that cannot degrade Cys‐Gly. The Arabidopsis cgp1 mutant had lower Cys‐Gly degradation activity than the wild type and showed perturbed concentrations of thiol compounds. Recombinant CGP1 showed reasonable Cys‐Gly degradation activity in vitro. Metabolomic analysis revealed that cgp1 exhibited signs of severe sulfur deficiency, such as elevated accumulation of O‐acetylserine (OAS) and the decrease in sulfur‐containing metabolites. Morphological changes observed in cgp1, including longer primary roots of germinating seeds, were also likely associated with sulfur starvation. Notably, At4g17830 has previously been reported to encode an N2‐acetylornithine deacetylase (NAOD) that functions in the ornithine biosynthesis. The cgp1 mutant did not show a decrease in ornithine content, whereas the analysis of CGP1 structure did not rule out the possibility that CGP1 has Cys‐Gly dipeptidase and NAOD activities. Therefore, we propose that CGP1 is a Cys‐Gly dipeptidase that functions in the cytosolic GSH degradation pathway and may play dual roles in GSH and ornithine metabolism. Significance Statement: In this study, we identified At4g17830 (CGP1) as a Cys‐Gly dipeptidase that functions in the glutathione (GSH) degradation pathway and revealed its importance in plant metabolism and growth, especially under sulfur starvation. Notably, CGP1 has been reported as an N2‐acetylornithine deacetylase (NAOD) that participates in the ornithine biosynthesis pathway; therefore, our findings imply that CGP1 is a bifunctional enzyme that plays vital roles in both sulfur and nitrogen metabolism. [ABSTRACT FROM AUTHOR]

SUMMARY: Meloidogyne incognita is one of the most widely distributed plant‐parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion. Virus‐induced gene silencing of MiCE108 impaired the parasitism of M. incognita in Nicotiana benthamiana. The ectopic expression of MiCE108 in Arabidopsis suppressed the deposition of callose, the generation of reactive oxygen species, and the expression of marker genes for bacterial flagellin epitope flg22‐triggered immunity, resulting in increased susceptibility to M. incognita, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst) DC3000. The MiCE108 protein physically associates with the plant defense protease RD21A and promotes its degradation via the endosomal‐dependent pathway, or 26S proteasome. Consistent with this, knockout of RD21A compromises the innate immunity of Arabidopsis and increases its susceptibility to a broad range of pathogens, including M. incognita, strongly indicating a role in defense against this nematode. Together, our data suggest that M. incognita deploys the effector MiCE108 to target Arabidopsis cysteine protease RD21A and affect its stability, thereby suppressing plant innate immunity and facilitating parasitism. [ABSTRACT FROM AUTHOR]

Water softening is a treatment process required to manage calcium and magnesium cations in water streams. Moreover, detection of such cations in water samples using simple portable techniques is required for monitoring and inspection of water quality. Nanocomposites can provide solutions for such multiple challenges while showing high performance and cost-effectiveness. In this work, the Cu-Fe layered double hydroxides (LDH)/cysteine-based electrodes were synthesized and are used as active materials for the electrochemical detection of calcium ions. The electrode materials were characterized using XRD, FTIR, and SEM. The synthesized electrode showed a limit of detection and a limit of quantification of 0.21 µM and 0.73 µM, respectively. The concentration range of detection was 5–30 µM. The intermolecular interactions of Ca ions with cysteine-free LDH and cysteine-LDH were investigated by Monte Carlo and molecular dynamics simulations. Monte Carlo simulations revealed that the (001) surface is favored for Ca(II) adsorption within the LDH structure with an energy of adsorption equals to 372.46 kcal/mol. This work paves the road towards developing cost-effective disposable electrode based on portable electrochemical detection of Ca ions for on-site water softening applications. [ABSTRACT FROM AUTHOR]

Purpose: High glucose (HG)-induced oxidative stress is associated with apoptosis in pancreatic β-cells. The protective effect of astaxanthin-s-allyl cysteine diester (AST-SAC) against HG-induced oxidative stress in pancreatic β-cells (βTC-tet cell line) in in vitro was studied. Materials and Methods: βTC-tet cell line was exposed to HG in the presence and absence of AST-SAC. Various parameters such as cell viability, reactive oxygen species generation, mitochondrial membrane potential, DNA fragmentation and expression of proteins involved in apoptosis [p53, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cytochrome c and caspase 3] were studied. Results: Pre-treatment of βTC-tet cells with AST-SAC (4, 8 and 12 μg/ml) in the presence of HG (25 mM) protected the viability of the cells in a dose-dependent manner. AST-SAC treatment mitigated the oxidative stress thereby preventing the mitochondrial dysfunction, DNA damage and apoptosis in βTC-tet cells against HG toxicity. Treatment with AST-SAC prevented the increased expression of p53 under HG conditions. Further, AST-SAC treatment maintained the level of pro-apoptotic (Bax, cleaved caspase-3 and cytochrome c) and anti-apoptotic (Bcl-2) proteins to that of the control level under HG exposed conditions in βTC-tet cells. Conclusion: Altogether, AST-SAC alleviated HG-induced oxidative damage and apoptosis in pancreatic β-cells by enhancing the antioxidant status and altering apoptotic-related protein expression. [ABSTRACT FROM AUTHOR]

In the ratiometric fluorescent (RF) strategy, the selection of fluorophores and their respective ratios helps to create visual quantitative detection of target analytes. This study presents a framework for optimizing ratiometric probes, employing both two-component and three-component RF designs. For this purpose, in a two-component ratiometric nanoprobe designed for detecting methyl parathion (MP), an organophosphate pesticide, yellow-emissive thioglycolic acid-capped CdTe quantum dots (Y-QDs) (analyte-responsive), and blue-emissive carbon dots (CDs) (internal reference) were utilized. Mathematical polynomial equations modeled the emission profiles of CDs and Y-QDs in the absence of MP, as well as the emission colors of Y-QDs in the presence of MP separately. In other two-/three-component examples, the detection of dopamine hydrochloride (DA) was investigated using an RF design based on blue-emissive carbon dots (B-CDs) (internal reference) and N-acetyl L-cysteine functionalized CdTe quantum dots with red/green emission colors (R-QDs/G-QDs) (analyte-responsive). The colors of binary/ternary mixtures in the absence and presence of MP/DA were predicted using fitted equations and additive color theory. Finally, the Euclidean distance method in the normalized CIE XYZ color space calculated the distance between predicted colors, with the maximum distance defining the real-optimal concentration of fluorophores. This strategy offers a more efficient and precise method for determining optimal probe concentrations compared to a trial-and-error approach. The model's effectiveness was confirmed through experimental validation, affirming its efficacy. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH), involves oxidative stress caused by the overproduction of reactive oxygen species (ROS). Small-molecule antioxidants have not been approved for antioxidant chemotherapy because of severe adverse effects that collapse redox homeostasis, even in healthy tissues. To overcome these disadvantages, we have been developing poly(ethylene glycol)- block -poly(cysteine) (PEG- block -PCys)-based self-assembling polymer nanoparticles (NanoCyses), releasing Cys after in vivo degradation by endogenous enzymes, to obtain antioxidant effects without adverse effects. However, a comprehensive investigation of the effects of polymer design on therapeutic outcomes has not yet been conducted to develop our NanoCys system for antioxidant chemotherapy. In this study, we synthesized different poly(L -cysteine) (PCys) chains whose sulfanyl groups were protected by tert -butyl thiol (S t Bu) and butyryl (Bu) groups to change the reactivity of the side chains, affording NanoCys(SS) and NanoCys(Bu), respectively. To elucidate the importance of the polymer design, these NanoCyses were orally administered to MASH model mice as a model of oxidative stress-related diseases. Consequently, the acyl-protective NanoCys(Bu) significantly suppressed hepatic lipid accumulation and oxidative stress compared to NanoCys(SS). Furthermore, we substantiated that shorter PCys were much better than longer PCys for therapeutic outcomes and the effects related to the liberation properties of Cys from these nanoparticles. Owing to its antioxidant functions, NanoCyses also significantly attenuated hepatic inflammation and fibrosis in the MASH mouse model. [Display omitted] [ABSTRACT FROM AUTHOR]

Cysteines (Cys) are chemically reactive amino acids containing sulfur that play diverse roles in plant biology. Recent proteomics investigations in Arabidopsis thaliana have revealed the presence of thiol post-translational modifications (PTMs) in several Cys residues. These PTMs are presumed to impact protein structure and function, yet mechanistic data regarding the specific Cys susceptible to modification and their biochemical relevance remain limited. To help address these limitations, we have conducted a wide-ranging analysis by integrating published datasets encompassing PTM proteomics (comparing S-sulfenylation, persulfidation, S-nitrosylation and S-acylation), genomics and protein structures, with a specific focus on proteins involved in plant lipid metabolism. The prevalence and distribution of modified Cys residues across all analyzed proteins is diverse and multifaceted. Nevertheless, by combining an evaluation of sequence conservation across 100+ plant genomes with AlphaFold-generated protein structures and physicochemical predictions, we have unveiled structural propensities associated with Cys modifications. Furthermore, we have identified discernible patterns in lipid biochemical pathways enriched with Cys PTMs, notably involving beta-oxidation, jasmonic acid biosynthesis, fatty acid biosynthesis and wax biosynthesis. These collective findings provide valuable insights for future investigations targeting the mechanistic foundations of Cys modifications and the regulation of modified proteins in lipid metabolism and other metabolic pathways. [ABSTRACT FROM AUTHOR]