Enhanced protection for interfacial lipid ozonolysis by sulfur-containing amino acids.

Sulfur-containing amino acids have been proposed as drugs for lipid oxidation associated with diseases for a long time, but the molecular-level mechanism on the effectiveness of sulfur-containing amino acids against lipid oxidation remains elusive. In this work, with the interfacial sensitivity mass spectrometry method, oxidation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), a widely used model lipid, was significantly inhibited on hung droplet surface in presence of sulfur-containing amino acids, such as cysteine (Cys) and methionine (Met). Both the Cys and Met showed a self-sacrificing protection. The amino acids with -S-R tails (R referring to methyl or t-butyl group) showed more effective against POPG oxidation than those with -SH tails, and this process was not related to the conformations of amino acids. The low effectiveness of Cys during the interfacial chemistry was proved to arise from the formation of disulfide bond. This study extends the current understanding of chemistry of sulfur-containing amino acids and provides insights to aid the sulfur-containing amino acids against cell oxidation.

Smartphone-assisted colorimetric biosensor for the rapid visual detection of natural antioxidants in food samples.

Quantitative monitoring of the concentrations of epigallocatechin gallate (EGCG) and cysteine (Cys) is of great significance for promoting human health. In this study, iron/aluminum bimetallic MOF material MIL-53 (Fe, Al) was rapidly prepared under room temperature using a co-precipitation method, followed by investigating the peroxidase-like (POD-like) activity of MIL-53(Fe, Al) using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate. The results showed that the Michaelis -Menten constants of TMB and H2O2 as substrates were 0.167 mM and 0.108 mM, respectively. A colorimetric sensing platform for detecting EGCG and Cys was developed and successfully applied for analysis and quantitative detection using a smartphone. The linear detection range for EGCG was 15∼80 µM (R2=0.994) and for Cys was 7∼95 µM (R2=0.998). The limits of detection (LOD) were 0.719 µM and 0.363 µM for EGCG and Cys, respectively. This work provides a new and cost-effective approach for the real-time analysis of catechins and amino acids.

Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe.

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Role of various virulence factors involved in the pathogenesis of Entamoeba histolytica.

Developing countries continuously face challenges to get rid of amoebiasis, a protozoan disease caused by Entamoeba histolytica. Every year around 900 million people get affected by amoebiasis, among them only 10 % of people show the symptoms of the disease while 90 % of people do not show any symptoms but still, serve as carriers of the disease. Asymptomatic persons carry cysts of Entamoeba in their fecal matter, which is carried by house flies to contaminate the food and water. Entamoeba histolytica is a very successful pathogen because it has very well-developed virulence factors that function in infection to host as well as in overcoming the host's immune response. However, researchers have very little information about the clear relationship between virulence factors and the virulence of Entamoeba histolytica, through various research, researchers have been able to identify key pathogenic factors that are crucial to the pathogenesis of amoebiasis and have provided valuable insights into the development of the disease. The objective of this review is to underscore various virulence factors (Monosaccharides, Gal/GalNAc lectin, extracellular vesicles, cysteine proteases, amoeba-pores, and actin microfilament) involved in pathogenesis which may be helpful for designing of future drug or therapy.

Systematic expression analysis of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 protein (CAP) superfamily in Arabidopsis.

The Cysteine-rich secretory proteins (CRISPS), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) protein (CAP) superfamily members are found in multiple eukaryotic organisms, including yeasts, animals, and plants. Although one of the plant CAP family genes, PR-1 is known to respond to pathogen infection in plants, the functions of other CAP family genes in Arabidopsis remain largely unknown. In this study, we conducted a comprehensive analysis of the similarities, loci, and expression patterns of 22 Arabidopsis CAP genes/proteins, providing a clue to elucidate their molecular functions. According to the promoter-ß-glucuronidase (GUS) analysis, members of the Arabidopsis CAP family were expressed in various young tissues or organs, such as root and shoot meristems, reproductive tissues, and particularly at the lateral root initiation site before the formation of the lateral root primordium, with distinct expression specificity. In particular, CAP51, CAP52, and CAP53 were specifically expressed in the cortical cells at the lateral root developing regions, suggesting that these genes may function in lateral root development. Thus, the expression patterns of Arabidopsis CAP family genes suggest that CAP family proteins may have certain function in the expressed organs or tissues in Arabidopsis plant.

Identification of Pathogenic Missense Mutations of NF1 Using Computational Approaches.

Neurofibromatosis type 1 (NF1) is a prevalent autosomal dominant disorder caused by mutations in the NF1 gene, leading to multisystem disorders. Given the critical role of cysteine residues in protein stability and function, we aimed to identify key NF1 mutations affecting cysteine residues that significantly contribute to neurofibromatosis pathology. To identify the most critical mutations in the NF1 gene that contribute to the pathology of neurofibromatosis, we employed a sophisticated computational pipeline specifically designed to detect significant mutations affecting the NF1 gene. Our approach involved an exhaustive search of databases such as the Human Gene Mutation Database (HGMD), UniProt, and ClinVar for information on missense mutations associated with NF1. Our search yielded a total of 204 unique cysteine missense mutations. We then employed in silico prediction tools, including PredictSNP, iStable, and Align GVGD, to assess the impact of these mutations. Among the mutations, C379R, R1000C, and C1016Y stood out due to their deleterious effects on the biophysical properties of the neurofibromin protein, significantly destabilizing its structure. These mutations were subjected to further phenotyping analysis using SNPeffect 4.0, which predicted disturbances in the protein's chaperone binding sites and overall structural stability. Furthermore, to directly visualize the impact of these mutations on protein structure, we utilized AlphaFold3 to simulate both the wild-type and mutant NF1 structures, revealing the significant effects of the R1000C mutation on the protein's conformation. In conclusion, the identification of these mutations can play a pivotal role in advancing the field of precision medicine and aid in the development of effective drugs for associated diseases.

N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.

OBJECTIVE: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH-wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo-angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib-dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. METHODS: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N-Acetyl-L-Cysteine (NAC) might be used to reduce senescence-associated adverse effects of axitinib treatment without altering its anti-tumor activity. RESULTS: We demonstrate that the use of the antioxidant molecule N-Acetyl-Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib-dependent toxicity. CONCLUSION: Overall, we found that NAC co-treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib-dependent toxicity.

Two-Dimensional Biodegradable l-Cysteine-Iodine Nanosheets for Computed Tomography-Guided Cancer Synergistic Sonodynamic Therapy and Chemotherapy.

Biodegradable versatile inorganic nanomaterials are highly desirable in the field of nanomedicine. Here, for the first time, we report a kind of novel two-dimensional biodegradable l-cysteine-iodine (l-Cys-I) nanosheet with high computed tomography (CT) imaging ability and sonosensitization efficacy. Such l-Cys-I nanosheets consist of iodine molecules and l-Cys, where the iodine molecules are coordinated and stabilized by l-Cys and cross-linked to form nanosheets through disulfide bonds. The large and convenient functional surface is further modified with targeting moieties DSPE-PEG-RGD and cancer drug doxorubicin (DOX) to construct a nanotheranostic nanoplatform (CIRD). Under ultrasound irradiation, the CIRD nanosheets assist in tremendous reactive oxygen species generation and controllable DOX release, leading to remarkable anticancer performance both in vitro and in vivo due to the synergistic sonodynamic therapy (SDT) and chemotherapy. Our results validate that the CIRD nanosheets enable effective body excretion and negligible systemic toxicity owing to the biodegradation properties. The CIRD nanosheets, with biodegradability, biocompatibility, and versatility, hold great promise in nanotheranostics.

Novel Colorimetric and Near-Infrared Ratiometric Fluorescent Probe for Sensing Cysteine in Food Samples, Plants, and Living Cells.

Cysteine (Cys) is a crucial biothiol that acts a significant function in food samples and biological systems, including plant roots and living cells. Hence, we developed a novel colorimetric and near-infrared ratiometric fluorescent probe (CT), composed of coumarin and tetrahydroacridine-conjugated indole salt, for the detection of Cys. Upon reaction with Cys, the probe undergoes a specific N-substitution reaction, resulting in a notable colorimetric change and a significant ratiometric fluorescent response in both visible and near-infrared emission channels. These dual-channel ratiometric fluorescence changes are completely independent, enabling the probe to obtain great selectivity, sensitivity, and exceptional detection accuracy. Leveraging these attributes, the probe was employed to provide accurate quantitative analysis of Cys in food samples. Furthermore, confocal imaging demonstrated that the probe could monitor both exogenous and endogenous Cys levels in living cells and track Cys changes in plant roots under heavy metal stress. This work presents a dependable and accurate imaging solution for tracking and identifying Cys of real food, plants, and living cells.

Multi-defense Pathways against Electrophiles through Adduct Formation by Low Molecular Weight Substances with Sulfur Atoms.

There is a variety of electrophiles in the environment. In addition, there are precursor chemicals that undergo metabolic activation by enzymes and conversion to electrophiles in the body. Although electrophiles covalently bind to protein nucleophiles, they also form adducts associated with adaptive or toxic responses. Low molecular weight compounds containing sulfur are capable of blocking such adduct formation by capturing the electrophiles. In this review, we present out findings on the capture and inactivation of electrophiles by 1) intracellular glutathione, 2) reactive sulfur species and 3) extracellular cysteine (formed during the production of sulfur adducts). These actions not only substantially suppress electrophilic activity but also regulate protein adduct formation.

Mammalian D-Cysteine controls insulin secretion in the pancreas.

D-amino acids are being recognized as important molecules in mammals with function. This is a first identification of endogenous D-cysteine in mammalian pancreas. D-cysteine is synthesized by serine racemase (SR) and SR-/- mice produce 6-10 fold higher levels of insulin in the pancreas and plasma including higher glycogen and ketone bodies in the liver. The excess insulin is stored as amyloid in secretory vesicles and exosomes. In glucose stimulated insulin secretion in mouse and human islets, equimolar amount of D-cysteine showed higher inhibition of insulin secretion compared to D-serine, another closely related stereoisomer synthesized by SR. In mouse models of diabetes (Streptozotocin (STZ) and Non Obese Diabetes (NOD) and human pancreas, the diabetic state showed increased expression of D-cysteine compared to D-serine followed by increased expression of SR. SR-/- mice show decreased cAMP in the pancreas, lower DNA methyltransferase enzymatic and promoter activities followed by reduced phosphorylation of CREB (S133), resulting in decreased methylation of the Ins1 promoter. D-cysteine is efficiently metabolized by D-amino acid oxidase and transported by ASCT2 and Asc1. Dietary supplementation with methyl donors restored the high insulin levels and low DNMT enzymatic activity in SR-/- mice. Our data show that endogenous D-cysteine in the mammalian pancreas is a regulator of insulin secretion.

Structure and functional studies of Avt1, a novel peptide from the sea anemone Aulactinia veratra.

Sea anemones are a rich source of peptide toxins spanning a diverse range of biological activities, typically targeting proteins such as ion channels, receptors and transporters. These peptide toxins and their analogues are usually highly stable and selective for their molecular targets, rendering them of interest as molecular tools, insecticides and therapeutics. Recent transcriptomic and proteomic analyses of the sea anemone Aulactinia veratra identified a novel 28-residue peptide, designated Avt1. Avt1 was produced using solid-phase peptide synthesis, followed by oxidative folding and purification of the folded peptide using reversed-phase high-performance liquid chromatography. The liquid chromatography-mass spectrometry profile of synthetic Avt1 showed a pure peak with molecular mass 6 Da less than that of the reduced form of the peptide, indicating the successful formation of three disulfide bonds. The solution structure determined by NMR revealed that Avt1 adopts an inhibitor cystine knot (ICK) fold, in which a ring is formed by two disulfide bonds with a third disulfide penetrating the ring to create the pseudo-knot. This structure provides ICK peptides with high structural, thermal and proteolytic stability. Consistent with its ICK structure, Avt1 was resistant to proteolysis by trypsin, chymotrypsin and pepsin, although it was not a trypsin inhibitor. Avt1 at 100 nM showed no activity in patch-clamp electrophysiological assays against several mammalian voltage-gated ion channels, but has structural features similar to toxins targeting insect sodium ion channels. Although sequence homologues of Avt1 are found in a number of sea anemones, this is the first representative of this family to be characterised structurally and functionally.

The conserved cysteines at position 18, 36, and 49 of Autographa californica multiple nucleopolyhedrovirus VP39 are essential for virus replication.

Autographa californica nucleopolyhedrovirus orf89 (vp39) encodes the major capsid protein VP39. Multiple alignments of protein sequences showed that VP39 has 8 conserved cysteine (Cys) residues. Cysteine residues play an important role in proper function of a protein. To determine the importance of these conserved cysteine residues for virus proliferation, a series of recombinant viruses harboring VP39-Cys mutants were constructed. Viral growth curves and transmission electron microscopy showed that mutation of Cys29, Cys132, Cys169, Cys229, or Cys232 of VP39 to alanine did not affect budded virion production; however, the mutation of Cys18, Cys36, or Cys49 to alanine resulted in interruption of capsid assembly. Co-immunoprecipitation assays showed that mutations of these 8 cysteines individually or simultaneously had no effect on self-association of VP39. Immunofluorescence analysis by confocal microscopy revealed that the subcellular localization of VP39 with mutations in Cys18, Cys36 or Cys49 was exclusively distributed in the cytoplasm of a cell regardless of virus infection or not, while the wild-type VP39 or the VP39 carrying mutations in Cys29, Cys132, Cys169, Cys229, or Cys232 was distributed throughout the cytoplasm and the nucleus. Our results demonstrated that Cys18, Cys36, and Cys49 are essential for the proper localization of VP39, which is a prerequisite for successful nucleocapsid assembly of the virus.

Evaluation of electrodeposition synthesis of gold nanodendrite on screen-printed carbon electrode for nonenzymatic ascorbic acid sensor.

Gold nanodendrite (AuND) is a type of gold nanoparticles with dendritic or branching structures that offers advantages such as large surface area and high conductivity to improve electrocatalytic performance of electrochemical sensors. AuND structures can be synthesized using electrodeposition method utilizing cysteine as growth directing agent. This method can simultaneously synthesize and integrate the gold nanostructures on the surface of the electrode. We conducted a comprehensive study on the synthesis of AuND on screen-printed carbon electrode (SPCE)-based working electrode, focusing on the optimization of electrodeposition parameters, such as applied potential, precursor solution concentration, and deposition time. The measured surface oxide reduction peak current and electrochemical surface area from cyclic voltammogram were used as the optimization indicators. We confirmed the growth of dendritic gold nanostructures across the carbon electrode surface based on FESEM, EDS, and XRD characterizations. We applied the SPCE/AuND electrode as a nonenzymatic sensor on ascorbic acid (AA) and obtained detection limit of 16.8 µM, quantification limit of 51.0 µM, sensitivity of 0.0629 µA µM-1, and linear range of 180-2700 µM (R2 value = 0.9909). Selectivity test of this electrode against several interferences, such as uric acid, dopamine, glucose, and urea, also shows good response in AA detection.

Design and Synthesis of Benzimidazole Carboxamide Cysteine Protease Inhibitors as Promising Anti-leishmanial Agents.

INTRODUCTION: More than 20 protozoan species of Leishmania are responsible for causing Leishmaniasis, an infection spread by blood-feeding phlebotomine sandflies. A narrow pool of drugs is currently available rendering the current drug stratagem to treat this infection . Development of novel, less toxic, and more effective regimens is thus a need of the hour. Design and synthesis of benzo[d]imidazole carboxamides as agents to combat Leishmaniasis are also required. METHODS: 14 benzo[d]imidazole carboxamides were synthesized and gauged against L. donovani promastigotes and intramacrophage amastigote forms. All of the tested compounds exhibited significant anti-promastigote properties with IC50 well below 10 uM. Compounds 4a, 4b, and 4d, showing the highest anti-parasitic activity against promastigote forms (IC50 0.91- 1.33 µM), were also found to be associated with better anti-leishmanial potential (IC50 0.78- 1.67 µM) against the intramacrophage amastigotes comparable to Amphotericin-B (0.13 µM), a drug used for Leishmaniasis. Compound (4a), namely N-(2-(trifluoromethyl)-1Hbenzo[ d]imidazol-5-yl)benzo[d][1,3]-5-carboxamide-dioxole, was found to be most potent against L. donovani amastigotes among all the tested compounds, and demonstrated better antileishmanial properties (IC50 0.78 µM) when compared to the standard. Compound 4a was also assessed for its toxicity profile against THP-1 human monocytic cells. To establish the molecular target(s) in silico, molecular docking studies were performed against cysteine protease, a putative virulence factor of Leishmania parasites, and nucleoside diphosphate kinase, an enzyme with a critical role in nucleotide recycling, also associated with resistance in Leishmania strains. Compound 4a showed better binding affinity than the standard to these targets; furthermore, the molecular dynamic simulation studies further affirmed the stability of compound 4a, within the active site of the targets. In vitro, cysteine protease inhibitory activity (IC50 8.53 µM) using Bz-Arg-AMC hydrochloride fluorogenic peptide substrate established the promising potential of 4a as a cysteine protease inhibitor. RESULT: Computational ADMET analysis indicated appropriate pharmacokinetic profile and physicochemical characteristics for all members of the synthesized library. CONCLUSION: Both in vitro and in silico studies indicate that the synthesized imidazole carboxamides can act as potent hits and that N-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5- yl)benzo[d][1,3]-5-carboxamide-dioxole 4a can be an effective hit molecule which can be further developed into potent lead molecule (s) to fight Leishmania donovani.

Promotion of RNF168-Mediated Nucleosomal H2A Ubiquitylation by Structurally defined K63-Polyubiquitylated Linker Histone H1.

The chemical synthesis of histones with homogeneous modifications is a potent approach for quantitatively deciphering the functional crosstalk between different post-translational modifications (PTMs). Here, we developed an expedient site-specific (poly)ubiquitylation strategy (CAEPL, Cysteine-Aminoethylation coupled with Enzymatic Protein Ligation), which integrates the Cys-aminoethylation reaction with the process of ubiquitin-activating enzyme UBA1-assisted native chemical ligation. Using this strategy, we successfully prepared monoubiquitylated and K63-linked di- and tri-ubiquitylated linker histone H1.0 proteins, which were incorporated into individual chromatosomes. Quantitative biochemical analysis of different RNF168 constructs on ubiquitylated chromatosomes with different ubiquitin chain lengths demonstrated that K63-linked polyubiquitylated H1.0 could directly stimulate RNF168 ubiquitylation activity by enhancing the affinity between RNF168 and chromatosome. Subsequent cryo-EM structural analysis of the RNF168/UbcH5c-Ub/H1.0-K63-Ub3 chromatosome complex revealed the potential recruitment orientation between RNF168 UDM1 domain and K63-linked ubiquitin chain on H1.0. Finally, we explored the impact of H1.0 ubiquitylation on RNF168 activity in the context of asymmetric H1.0-K63-Ub3 di-nucleosome substrate, revealing a comparable stimulation effect of both the inter- and intra-nucleosomal crosstalk. Overall, our study highlights the significance of access to structurally-defined polyubiquitylated H1.0 by CAEPL strategy, enabling in-depth mechanistic investigations of in-trans PTM crosstalk between linker histone H1.0 and core histone H2A ubiquitylation.

Advances in Cysteine Protease B Inhibitors for Leishmaniasis Treatment.

The expression and release of cysteine proteases by Leishmania spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting Leishmania parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant (Ki) and half maximal inhibitory concentration (IC50) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 µM, respectively. On the other hand, all peptidic compounds evaluated for Ki (43.8%) and IC50 (31.3%) obtained values < 1 µM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis.

A radioactive and fluorescent dual modality cysteine cathepsin-B activity-based probe for the detection and treatment evaluation in rheumatoid arthritis.

Activated macrophages are key effector cells and specific markers in patients with rheumatoid arthritis (RA). Cysteine cathepsin B (CTS-B) is highly expressed in macrophages and positively associated with RA activity and severity. This study aims to evaluate an activity-based multi-modality diagnostic agent, 68Ga-BMX2, which targets CTS-B to visualize the arthritis activity and evaluate the treatment efficacy. A CTS-B activity-based probe, BMX2, was labeled efficiently with 68Ga to produce 68Ga-BMX2 for fluorescent and positron emission tomography (PET) multi-modality imaging. The affinity and specificity of BMX2 binding with the CTS-B enzyme in macrophages were determined by radioactive experiment using RAW 264.7 cell lines, with CA074 and BMX5 as the inhibitors to test the specificity of the binding. Then, PET and fluorescence imaging were acquired on collagen-induced arthritis (CIA) mice. Additionally, the treatment monitoring capability of 68Ga-BMX2 PET/CT imaging was tested with methotrexate (MTX). RAW 264.7 macrophage cells showed significant uptake of 68Ga-BMX2. The binding of BMX2 with CTS-B in RAW 264.7 macrophage cells is time-dependent and could be blocked by CA074 and BMX5. In vivo optical and PET imaging showed high signals in the right hind arthritis in CIA mice from 68Ga-BMX2 and BMX2 accumulated for at least 120 h. Additionally, 68Ga-BMX2 signals were significantly reduced in the MTX-treated CIA mice compared to the control group. The 68Ga-BMX2, a radioactive and fluorescent dual-modality diagnostic agent targeting CTS-B, demonstrated a practical approach for CIA PET and fluorescence imaging. The 68Ga-BMX2 multimodality imaging could significantly monitor the treatment response in the CIA mice.

Investigating the Effects of Pink-Generating Ligands on Enhancing Color Stability and Pigment Properties in Pork Sausage Model Systems Cured with Sodium Nitrite or White Kimchi Powder.

In this study, we investigated the effects of different nitrite sources (sodium nitrite or white kimchi powder) and pink-generating ligands (cysteine, histidine, or nicotinamide) on the development and stability of cured meat color in pork sausage model systems over 30 d of refrigerated storage. The samples were prepared in a 2 × 3 factorial design with two nitrite sources and three ligands, and their physicochemical properties were evaluated on days 0, 15, and 30. Although white kimchi powder induced cured color development similar to that of synthetic sodium nitrite, it resulted in higher cooking loss and lower residual nitrite content in cured pork sausages (p < 0.05). The addition of cysteine resulted in significantly higher CIE a* values, cured meat pigment, and curing efficiency than histidine and nicotinamide (p < 0.05), while yielding lower pH values, residual nitrite content, and total pigment content (p < 0.05). The storage duration significantly reduced the residual nitrite and total pigment contents of the products. These findings suggest that white kimchi powder can serve as a natural alternative to sodium nitrite in pork sausage models and that the incorporation of cysteine has a favorable impact on the development and enhancement of cured meat color.

The Facile Production of p-Chloroaniline Facilitated by an Efficient and Chemoselective Metal-Free N/S Co-Doped Carbon Catalyst.

The catalytic hydrogenation of the toxic and harmful p-chloronitrobenzene to produce the value-added p-chloroaniline is an essential reaction for the sustainable chemical industry. Nevertheless, ensuring satisfactory control of its chemoselectivity is a great challenge. In this work, a N/S co-doped metal-free carbon catalyst has been fabricated by using cysteine as a source of C, N, and S. The presence of calcium citrate (porogen agent) in the mixture subjected to pyrolysis provided the carbon with porosity, which permitted us to overcome the issues associated with the loss of heteroatoms during an otherwise necessary activation thermal treatment. Full characterization was carried out and the catalytic performance of the metal-free carbon material was tested in the hydrogenation reaction of p-chloronitrobenzene to selectively produce p-chloroaniline. Full selectivity was obtained but conversion was highly dependent on the introduction of S due to the synergetic effect of S and N heteroatoms. The N/S co-doped carbon (CYSCIT) exhibits a mesoporous architecture which favors mass transfer and a higher doping level, with more exposed N and S doping atoms which act as catalytic sites for the hydrogenation of p-chloronitrobenzene, resulting in enhanced catalytic performance when compared to the N-doped carbon obtained from melamine and calcium citrate (MELCIT) used as a reference.