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This study presents a method for recovering scandium from Indonesian bauxite residue (red mud) through a sulfation roasting-assisted water leaching process. Ammonium sulfate, (NH4)2SO4, was chosen as the sulfate source for its lower melting point, less corrosivity, decreased toxicity, and the potential for ammonia recovery. A modified mixing system was introduced to improve the distribution of (NH4)2SO4 on red mud particles by combining them in water. A series of experiments were conducted to optimize the sulfation roasting process by examining the effects of the (NH4)2SO4/red mud ratio, temperature, and roasting time. Subsequently, water leaching was optimized while considering the effect of leaching time and liquid-to-solid (L/S) ratio. The leaching of scandium from the roasted red mud showed rapid kinetics, even when using only water. Under the roasting conditions of 1/1 (g/g) (NH4)2SO4/red mud ratio, 700°C, 60 min roasting time, and the leaching conditions of 65°C, 60 min, and 10 mL/g (L/S), over 90% of scandium was recovered, along with 64.4% Al leaching and below 8% Fe leaching. These results were further corroborated through comprehensive analyses such as x-ray diffraction (XRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS). This study offers insights into an alternative, more environmentally friendly method for Sc recovery from red mud, promoting the sustainable use of hazardous waste like red mud. [ABSTRACT FROM AUTHOR]

The limited self-repair capacity of cartilage due to its avascular and aneural nature leads to minimal regenerative ability. Autologous chondrocyte transplantation (ACT) is a popular treatment for cartilage defects but faces challenges due to chondrocyte dedifferentiation in later passages, which results in undesirable fibroblastic phenotypes. A promising treatment for cartilage injuries and diseases involves tissue engineering using cells (e.g., chondrocytes), scaffolds (e.g., Alginate Sulfate (AlgSulf)), and biochemical signals (e.g., Salidroside and TGF-β). This study focuses on investigating the effects of AlgSulf scaffolds with varying degrees of sulfation, Salidroside, and TGF-β on the proliferation, viability, and phenotype maintenance of chondrocytes. The findings demonstrate that AlgSulf films with a degree of sulfation (DS) = 2, treated with a combination of Salidroside and TGF-β, significantly enhanced chondrocyte proliferation (p < 0.001 and p < 0.0001 in P2 and P4, respectively), preserved round cell morphology, and maintained cartilage-specific gene expression (Col2, Aggrecans, and SOX9) while downregulating fibroblastic markers (Col1, MMP13, IL-1β, and IL-6). Our findings suggest the potential of this combination for enhancing cartilage regeneration in tissue engineering applications. [ABSTRACT FROM AUTHOR]

Posttranslational modifications (PTMs) are potential critical quality attributes in biotherapeutic development, as they can affect drug efficacy and safety. Tyrosine sulfation plays a critical role in protein–protein interactions and has been found on many surface receptors as well as antibody complementarity-determining regions (CDR). However, the presence and function of tyrosine sulfation in therapeutic proteins have not been broadly investigated due to difficulties in detecting the modification. Here, we establish an integrated strategy to identify tyrosine sulfation in biotherapeutic proteins. In silico prediction was used to estimate possible modification sites, followed by the elucidation with intact LCMS and native SCX–MS. The combination of these three steps takes less than 1 h, which provides quick and confident preliminary detection of potential CQAs. Taking NB1 as an example, three +80 Da mass shifts were observed from intact mass analysis and three acidic peaks were monitored by SCX, allowing confirmation of modification as either phosphorylation or sulfation. Peptide mapping, Fe3+-IMAC enrichment, and dephosphorylation were further conducted to provide improved signal intensity and differentiation of modification such as sulfation or phosphorylation. With this integrated strategy, we were able to identify for the first time both tyrosine sulfation and serine phosphorylation in one therapeutic protein. [ABSTRACT FROM AUTHOR]

This work describes the diagnostic study on the building materials, mostly carbonated, belonging to Santa Maria Cathedral and the Medieval Wall of Vitoria‐Gasteiz (Spain) with the aim to design the best conservation procedure. Both the studies of the lithology and the secondary compounds originated by environmental impacts on the Cathedral and on the Medieval Wall were carried out using laboratory instruments (μ‐Raman and micro‐energy‐dispersive X‐ray spectroscopy, X‐ray diffraction and ion chromatography) on selected samples provided by the restorers. The systematic presence of black crusts in the stones of the Cathedral was related to the growth of microcrystalline structures of secondary compounds and biological patinas and the deposition of atmospheric particles from traffic and house heating systems. In fact, the main components identified were carbon, and iron compounds such as hematite, goethite, magnetite and lepidocrocite. In addition, the detection of lead compounds (lead‐rich hydroxyapatite) suggested in the same way the impact of the urban environment on the degradation and blackening of stone materials. The presence of sulfates, mainly gypsum, and, to a lesser extent, epsomite, anhydrite and bloedite could be caused by the sulfation of carbonated compounds as a result of an acid attack of atmospheric pollutants. The results on the secondary products of the Medieval Wall showed a greater presence of degradation by microorganisms compared to the Cathedral. This is probably related to the large garden surrounding the fortification, where the grass is in direct contact to the lower part of the structure. Markers of biological activity, such as carotenoid pigments and calcium oxalate weddellite, together with other soluble oxalates were identified. The presence of ammonium nitrate, characterised by means ion chromatography, causes a chemical degradation of carbonate stone materials over time, due to the acidic nature of the ammonium ion. In both cases considered in this study, the presence of nitrate compounds, nitratine and potassium nitrate, was attributed to both natural factors (ammonium nitrate is coming from the decomposition of plant and animal excretions), and anthropogenic contamination. [ABSTRACT FROM AUTHOR]

Aberrant protein glycosylation is a hallmark alteration of cancer and is highly associated with cancer progression. Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, but the N-glycosylation of its glycoproteins has not been well characterized. In this work, we analyzed multiple freshly prepared PTC specimens along with paired normal tissue obtained from thyroidectomies. Glycomic analyses focused on Asn-linked (N)-glycans and employed mass spectrometry (MS), along with Western blot approaches of total solubilized materials that were examined for binding by specific lectins and a monoclonal antibody (mAb) O6, specific for 3-O-sulfated galactose residues. We observed major differences in PTC versus paired normal specimens, as PTC specimens exhibited higher levels of N-glycan branching and bisection with N-acetylglucosamine residues, consistent with RNAseq data. We also found that 3-O-sulfated galactose was present in N-glycans of multiple glycoproteins from both PTC and control specimens, as recognized by the O6 mAb and as confirmed by MS analyses. These results provide new insights into the N-glycans present in glycoproteins of thyroid cancer and context for further studies of these altered glycans as biomarkers and targets for therapeutics. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to describe the pharmacokinetics of paracetamol and its metabolites in extreme preterm neonates in the context of patent ductus arteriosus treatment. Factors associated with inter-individual variability and metabolic pathways were studied. The association between drug exposure and clinical outcomes were investigated. Methods: Preterm neonates of 23–26 weeks' gestational age received paracetamol within 12 h after birth. Plasma concentrations of paracetamol and its metabolites were measured throughout 5 days of treatment. Clinical success was defined as ductus closure on two consecutive days or at day 7. Aspartate aminotransferase and alanine aminotransferase levels were used as surrogates for liver damage. Results: Data from 30 preterm neonates were available for pharmacokinetic analysis. Paracetamol pharmacokinetics were described using a two-compartment model with significant positive effects of weight on clearance and of birth length on peripheral compartment volume. Paracetamol was mainly metabolised into sulphate (89%) then glucuronide (6%), and the oxidative metabolic pathway was reduced (4%). The glucuronidation pathway increased with gestational age, whereas the sulfation pathway decreased. No difference was observed in drug exposure between successful and unsuccessful patients. No increase in aspartate aminotransferase and alanine aminotransferase levels were observed during treatment, and no association was found with either paracetamol or oxidative metabolite exposures. Conclusion: The relative proportions of the metabolic pathways were characterised with gestational age. In the range of observed drug exposures, no association was found with clinical response or liver biomarkers. These findings may suggest that paracetamol concentrations were within the range that already guarantee a maximum effect on ductus closure. [ABSTRACT FROM AUTHOR]

Carrageenans are polysaccharides from red algae which are widely used as food additives and in other applications. Their structure is often described by different disaccharide repeating units, although it was already demonstrated that reality is more complex. In many studies, commercial carrageenans were used to establish structure function relationships, but a structural and compositional analysis was rarely conducted. Therefore, the aim of our study was to systematically and comprehensively characterize a broad collection of commercial carrageenans with different specifications from different manufacturers. For a more detailed characterization, an analytical approach based on partial enzymatic hydrolysis in combination with HPLC–MS and HPSEC-RI was developed and applied. Furthermore, rheology was used to gain detailed insights into the functionality of selected samples. Our results demonstrate that significant structural variation can be observed for commercial carrageenans. The samples contained different cations and the carrageenan type specified by the manufacturer did not always represent the structure of the corresponding polysaccharides. This was especially true for λ-carrageenans: Of the six commercial samples analyzed, none contained structural elements from the λ-type. Instead, the corresponding carrageenans contained κ-, ι- and ν-units. The application of the developed enzymatic-chromatographic approach showed that different hybrid carrageenans are present. In addition, the rheological analysis of the commercial carrageenan samples showed clear differences in the gelling properties upon calcium addition which could influence their behavior in different applications. Our results demonstrate that before an investigation of structure–function relationships, commercial carrageenan samples should be analyzed for their structure and composition. We also showed that the enzymatic-chromatographic approach described in this study is well suited for this purpose. [ABSTRACT FROM AUTHOR]

The fibroblast growth factor-2 (FGF-2) is a critical protein for biological processes such as angiogenesis and tissue regeneration. Recently, hydrogels based on semi-synthetic sulfated polysaccharides have been developed for the controlled delivery of FGF-2. These affinity-based FGF-2 carriers utilizing hydrogels based on sulfated polysaccharides enable sustained delivery of FGF-2, yet choice of materials is limited. Here, we demonstrate a novel synthetic sulfated polysaccharide-based hydrogel based on bacterial polyglucuronic acid (PGU). We synthesized phenol-grafted sulfated PGU (PGUS-Ph), an enzymatically cross-linkable PGU derivative that exhibited an enhanced affinity for FGF-2. The aqueous solution of PGUS-Ph, when combined with FGF-2, could be injected into affected sites and form a hydrogel in a minimally invasive manner. The FGF-2 released from the PGUS-Ph hydrogel induced blood vessel formation, as proven by a chick embryo-based angiogenesis assay. Our results indicate that the PGUS-Ph has the potential as an enzymatically cross-linkable and minimally invasively injectable affinity-based FGF-2 delivery system. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Over the past two decades, the global incidence of gout has markedly increased, affecting people worldwide. Considering the side effects of xanthine oxidase (XO) inhibitor drugs (e.g. allopurinol and febuxostat) used in the treatment of hyperuricemia and gout, the potential application of phytochemicals has been widely studied. In addition, XO also takes part in the elimination of certain drugs, including 6‐mercaptopurine. In the current explorative study, we aimed to examine the potential effects of tea catechins, resveratrol, silymarin flavonolignans and some of their conjugated metabolites on XO‐catalyzed xanthine and 6‐mercaptopurine oxidation, applying in vitro assays and modeling studies.Catechins, resveratrol and resveratrol conjugates exerted no or only weak inhibitory effects on XO. Silybin A, silybin B and isosilybin A were weak, silychristin was a moderate, while 2,3‐dehydrosilychristin was a potent inhibitor of the enzyme. Sulfate metabolites of silybin A, silybin B and isosilybin A were considerably stronger inhibitors compared to the parent flavonolignans, and the sulfation of 2,3‐dehydrosilychristin slightly increased its inhibitory potency. Silychristin was the sole flavonolignan tested, where sulfate conjugation decreased its inhibitory effect.2,3‐Dehydrosilychristin seems to be a promising candidate for examining its in vivo antihyperuricemic effects, because both the parent compound and its sulfate conjugate are highly potent inhibitors of XO. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Many relevant metabolites, as well as chemical commodities, contain at least one sulfate ester group. Consequently, biocatalytic strategies to attach sulfate to a molecule under mild conditions are of high interest. In order to expand the enzymatic toolbox available, five new arylsulfate sulfotransferases (ASSTs) were identified in this study. Overexpression in Escherichia coli and enzyme purification resulted in soluble proteins which catalyzed the sulfate transfer to an acceptor substrate using p-nitrophenyl sulfate (pNPS) as sulfate donor. Optimal reaction conditions were established with respect to temperature and pH, as well as their tolerance to organic co-solvents and melting temperature. Additionally, the kinetic parameters (Vmax, KM, and kcat) were determined. The substrate scope for the acceptor showed that a structurally diverse spectrum of alcohols is accepted. The substrates included phenolic alcohols with one, two, and three hydroxy groups, linear and cyclic aliphatic alcohols, and amines. The phenolic substrates were accepted reaching activities of up to 154 U/mg purified enzyme. Additionally, also the aliphatic alcohols (both linear and cyclic) were accepted at reduced activity, showing that these enzymes are not limited to phenolic alcohols. Moreover, catalytic activity was detected when using aniline as an acceptor substrate implying their ability to sulfate also amino groups. Finally, the consecutive sulfation of di- and trihydroxy compounds was observed, resulting in the detection of the corresponding disulfated molecules. Key points: • Five novel arylsulfate sulfotransferases were identified and characterized. • Accepted substrates included aromatic and aliphatic alcohols, as well as aniline. • Disulfation of di- and trihydroxy aromatic compounds was studied and confirmed. [ABSTRACT FROM AUTHOR]

Osteoporosis is a degenerative bone disease highly prevalent in older women, causing high morbidity and mortality rates. Fourteen kinds of fucoidan were isolated from Sargassum fusiforme through acid (named as SFS), alkaline (SFJ) and water (SFW). SFW was passed through an anion exchange column to obtain SFW-0, SFW-0.5 and SFW-2. SFW-0.5 and SFW-2 were degraded to obtain different sulfate group contents SFW-x-M/S/O (x for 0.5 or 2). We further confirmed SFW-0.5-O was the most effective fraction of SFW. SFW-0.5-O may have alternating backbones of (Gal)n and (Fuc)n, and the main sulfation may be at C2/C3 of the Fuc/Gal residues. SFW-0.5-O inhibition of OC differentiation was associated with IRF-8 signaling; meanwhile, SFW-0.5-O promoted osteoblast differentiation and bone mineral nodule formation. SFW-0.5-O also effectively ameliorated osteoporosis symptom caused by estrogen deprivation in vivo. We uncovered that the fucoidan active fraction SFW-0.5-O demonstrated effective bone protection, may be exploited for osteoporosis therapy. Fucoidan active ingredient SFW-0.5-O can effectively inhibit osteoclastogenesis, promote osteoblast differentiation, and improve osteoporosis symptoms caused by estrogen deprivation. [ABSTRACT FROM AUTHOR]

Fucoidan, a sulfated polysaccharide found primarily in brown algae, is known for exhibiting various biological activities, many of which have been attributed to its sulfate content. However, recent advancements in techniques for analyzing polysaccharide structures have highlighted that not only the sulfate groups but also the composition, molecular weight, and structures of the polysaccharides and their monomers play a crucial role in modulating biological effects. This review comprehensively provides the monosaccharide composition, degree of sulfation, molecular weight distribution, and linkage of glycosidic bonds of fucoidan, focusing on the diversity of its biological activities based on various characteristics. The implications of these findings for future applications and potential therapeutic uses of fucoidan are also discussed. [ABSTRACT FROM AUTHOR]

Sulfation is a highly valuable pathological and physiological process, yet it is often underappreciated considering the rather difficult accessibility of organosulfates. O‐sulfonation (O−SO3), a conventional and still common way to make organosulfates, restricts its applicability to hydroxyl compounds and therein lies a major challenge of library construction. Here, we describe a benzylic C−H radical sulfation with persulfates via C−O bond formation. This strategy leverages modular control over the reactivity of persulfates and the stability of sulfate radicals by coutercations. K+/NH4+ stabilized sulfate radicals act as the oxidant to generate carbon‐centered radicals from substrates, and activation of persulfates by n‐NBu4+ provides O−O resource pool to facilitate C−OSO3− bond formation via a bimolecular homolytic substitution (SH2) process. [ABSTRACT FROM AUTHOR]

Rationale: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti‐osteoporotic mechanism are still unclear, restricting its development and application. Methods: Ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti‐osteoporosis targets and mechanism were predicted using network pharmacology. Results: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan‐ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K‐Akt signaling pathway, estrogen signaling pathway, and so on. Conclusions: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti‐osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Complexation with sulfated glycosaminoglycans (GAGs) regulates the signaling of pro‐angiogenic growth factors in vivo. To use this principle in modulating microvascular network formation and stability in vitro, a library of biohybrid hydrogels containing heparin, a highly sulfated GAG, or its selectively desulfated derivatives, is prepared. The hydrogels are applied to systematically investigate the effects of GAG concentration and sulfation patterns on embedded cultures of human umbilical vein endothelial cells (HUVECs) and cocultures of HUVECs with mesenchymal stromal cells (MSCs). Formation and morphology of microvascular networks, stromal cell expansion, and extracellular matrix (ECM) protein deposition are found to be significantly influenced by the hydrogel's GAG concentrations and sulfation patterns, presumably through differences in the resulting availability and bioactivity of GAG‐binding growth factors. In particular, cocultures in hydrogels with either low heparin concentration (500 µm) or higher concentrations of heparin desulfated at the 6O or N position resulted in the formation of dense, stable microvascular networks. The respective conditions also displayed enhanced stromal cell proliferation and ECM protein deposition, leading to increased matrix stiffness. Therefore, precisely tuning the affinity of biohybrid materials for pro‐angiogenic factors effectively enhances the vascularization of engineered tissue constructs in vitro. [ABSTRACT FROM AUTHOR]

Certain human papillomaviruses (HPVs) are etiological agents for several anogenital and oropharyngeal cancers. During initial infection, HPV16, the most prevalent cancer-causing type, specifically interacts with heparan sulfates (HSs), not only enabling initial cell attachment but also triggering a crucial conformational change in viral capsids termed structural activation. It is unknown, whether these HPV16-HS interactions depend on HS sulfation patterns. Thus, we probed potential roles of HS sulfations using cell-based functional and physicochemical assays, including single-molecule force spectroscopy. Our results demonstrate that N-sulfation of HS is crucial for virus binding and structural activation by providing high-affinity sites, and that additional 6O-sulfation is required to mechanically stabilize the interaction, whereas 2O-sulfation and 3O-sulfation are mostly dispensable. Together, our findings identify the contribution of HS sulfation patterns to HPV16 binding and structural activation and reveal how distinct sulfation groups of HS synergize to facilitate HPV16 entry, which, in turn, likely influences the tropism of HPVs. [ABSTRACT FROM AUTHOR]

In this study, the recovery of rare earth elements (REEs) from red mud (bauxite residue) was explored through a combination of citric acid leaching and sulfation roasting–water leaching processes, introducing an innovative approach to the field. The research uniquely investigates the influence of citric acid on the leaching behavior of REEs and impurities in both untreated red mud and red mud subjected to sulfation roasting, providing a direct comparison of these methodologies. A novel aspect of this study is the evaluation of solvent extraction efficiency using DEHPA, highlighting the selective recovery of REEs over impurities from both citric acid and water-leaching solutions. Furthermore, a comprehensive phase analysis using X-ray diffraction (XRD) was conducted to track the transformations of minerals during the sulfation roasting process, an original contribution to the literature. The findings revealed that over 85% of REEs and major elements such as Fe, Al, Ca, and Ti dissolved in water after sulfation at 105 °C, while iron and titanium dissolution significantly decreased following roasting at 725 °C. Importantly, terbium, neodymium, and gadolinium extraction efficiencies were notably affected by roasting temperature. Citric acid leaching results demonstrated that the direct leaching of red mud leads to higher leaching efficiency than leaching it after the roasting process. Solvent extraction demonstrated lower terbium and neodymium recovery from citric acid solutions compared to water leaching solution. Finally, stripping experiments illustrated that 6M H2SO4 solution is capable of stripping more than 80% of rare earth elements, except terbium. [ABSTRACT FROM AUTHOR]

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1. Ligand activation of CCR5, not CCR1, drastically improves in the absence of glycosaminoglycans (GAGs). Ligand activity at both CCR1 and CCR5 is boosted by positively charged/basic peptides shown to interact with acidic chemokine receptor N-termini. We propose that receptors with an inherent low N-terminus acidity rely on post-translational modifications (PTMs) to efficiently compete with acidic entities in the local environment for ligand capture. Although crucial for initial ligand binding, strong electrostatic interactions between the ligand and the receptor N-terminus may counteract following insertion of the ligand into the receptor binding pocket and activation, a process that seems to be aided in the presence of basic peptides. Basic peptides bind to the naked CCR1 N-terminus, not the CCR5 N-terminus, explaining the loss of boosting of ligand-induced signaling via CCR5 in cells incapable of glycosylation. [ABSTRACT FROM AUTHOR]

Sinomenium acutum (Thunb.) Rehd. et Wils is widely used in the treatment of rheumatoid arthritis, with its alkaloid compound sinomenine (SIN) being renowned for its significant anti‐inflammatory properties. However, despite its widespread application, the in vivo anti‐inflammatory mechanisms and metabolic pathways of SIN remain incompletely understood. This study established a rapid and reliable method based on an ultra‐high‐performance liquid chromatography method coupled with Quadrupole‐Exactive Orbitrap mass spectrometry and molecular docking to identify and characterize SIN and 69 metabolites in rat plasma, urine, and feces, revealing primary metabolic pathways of hydroxylation, demethylation, sulfation, and glucuronidation. Molecular docking results revealed that phase I reactions, including dedimethylation, demethylation, dehydrogenation, and dihydroxylation, along with their composite reactions, were pivotal in influencing SIN's in vivo anti‐inflammatory activity. M28, M36, and M59 are potentially the most anti‐inflammatory active metabolites of SIN in vivo. This comprehensive analysis unveils SIN's metabolic pathways, offering insights into its biological processes and suggesting a novel approach for exploring active drug constituents. These findings pave the way for further understanding SIN's anti‐inflammatory mechanisms, contributing significantly to the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Based on the concept of environmentally friendly production, five kinds of sulfeted castor oil with different organically combined sulfuric anhydride were successfully prepared by sulfur trioxide membrane sulfonation process instead of the traditional concentrated sulfuric acid process, which solved the problem of waste acid and waste inorganic salts in the traditional preparation process・ The successful preparation of sulfated castor oil was demonstrated by means of infrared spectroscopy and chemical analysis. The properties of five sulfated castor oils with different organically combined sulfuric anhydride, namely surface tension, dynamic surface tension, emulsifying power, particle size and leather fatliquoring applica・ tion, were studied and compared with commercially available products・ The results showed that compared with the commercially available products, the sulfated castor oil prepared by SO3 process had better surface activity, with a minimum y沁 of 43 ・ 0 mN/m, a cmc of 9 ・ 3 mg/L, good emulsifying power, a particle size of less than 200 nm, and excellent fatliqouring performance. [ABSTRACT FROM AUTHOR]

The employment of Mazidagi phosphate ore for wet flue gas desulphurization was investigated. The ore was exposed to sulfation processes in a three-phase double-stirred reactor to determine the effects of certain parameters on SO2 absorption. The absorption rate significantly increased with inlet SO2 concentration, gas flow rate, stirring speeds, and solid concentration but not with temperature. The absorption rate increases as the mass transfer coefficients and interface area value increase with stirring speeds. These parameters have also a prominent impact on the absorption rate depending on the dissolution rate of CaCO3. Based on these, the most effective parameters on SO2 absorption are liquid-phase stirring speed and suspension concentration, and the process is diffusion-controlled in the liquid phase. In addition, optimum conditions were determined, and then the ore was exposed to sulfation processes via a semi-batch operation mode. A comparison between raw and sulfated ore was examined for the changes in physical structure and chemical composition. Although the ratios of fluorapatite and carbonate-fluorapatite remained nearly constant, the ratio of calcite decreased significantly. It was determined from these investigations that the calcite in the phosphate ore has been converted into the CaSO3∙½H2O compound. Consequently, both the calcite in the phosphate ore was utilized effectively for wet flue gas desulphurization, and a phosphate-rich industrial product was obtained. [ABSTRACT FROM AUTHOR]

Tumor extracellular matrices (ECM) exhibit aberrant changes in composition and mechanics compared to normal tissues. Proteoglycans (PG) are vital regulators of cellular signaling in the ECM with the ability to modulate receptor tyrosine kinase (RTK) activation via their sulfated glycosaminoglycan (sGAG) side chains. However, their role on tumor cell behavior is controversial. Here, it is demonstrated that PGs are heavily expressed in lung adenocarcinoma (LUAD) patients in correlation with invasive phenotype and poor prognosis. A bioengineered human lung tumor model that recapitulates the increase of sGAGs in tumors in an organotypic matrix with independent control of stiffness, viscoelasticity, ligand density, and porosity, is developed. This model reveals that increased sulfation stimulates extensive proliferation, epithelial‐mesenchymal transition (EMT), and stemness in cancer cells. The focal adhesion kinase (FAK)‐phosphatidylinositol 3‐kinase (PI3K) signaling axis is identified as a mediator of sulfation‐induced molecular changes in cells upon activation of a distinct set of RTKs within tumor‐mimetic hydrogels. The study shows that the transcriptomic landscape of tumor cells in response to increased sulfation resembles native PG‐rich patient tumors by employing integrative omics and network modeling approaches. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration–time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity. [ABSTRACT FROM AUTHOR]

The present study presents the results obtained from evaluating the photocatalytic behavior of a series of sulfated CeO2 materials in the photocatalytic degradation of the herbicide 2,4-dichlorophenoxyacetic acid. The CeO2 photocatalytic support was prepared using the precipitation synthesis method. Subsequently, the support was wetly impregnated with different contents of sulfate ions (0.5, 1.0, and 2.0 wt.%). The materials were characterized using X-ray diffraction, nitrogen physisorption, infrared spectroscopy, diffuse reflectance UV–Vis spectrophotometry, and thermal analysis. The characterization results showed that the sulfation of the material promoted an increase in the surface area and a decrease in the average size of the crystallites. Likewise, it was possible to demonstrate the surface sulfation of the support through bidentate coordination of the sulfate groups to the semiconductor metal. Concerning photoactivity, the convenience of the surface modification of CeO2 was confirmed because the sulfate groups acted as capturers of the electrons generated during the photocatalytic process, reducing the frequency of recombination of the charge carriers and allowing the availability of the gaps to favor the degradation reaction of the contaminant. Finally, it was evident that a percentage of 1.0 wt.% of the sulfate anion is the optimal content to improve the photocatalytic properties of CeO2. [ABSTRACT FROM AUTHOR]

The phase transformation and vanadium leaching mechanism of stone coal during two blank calcined stages are systematically studied. Composition, structure, and morphology of the materials are analyzed by ICP‐AES, BPMA, XRD, FTIR, and SEM. The results show that the main components of stone coal are SiO2, C, aluminosilicate and FeS2, V2O5 is 0.70%. Two‐stage roasting is a process of deformation, melting, and reconstruction of stone coal, the oxidation of pyrite, decomposition of aluminosilicate, sulfation of calcite, combustion of carbon and the formation of calcium vanadate occur in the first stage, the oxidation of low‐price vanadium occurs in the second stage. At −0.074 mm ≥90%, liquid solid ratio 1.5:1, 10% sulfuric acid reaction at room temperature for 3 h, the vanadium leaching rate in each material is in the order of roasting slag>decarbonized slag>stone coal. [ABSTRACT FROM AUTHOR]

Proteoglycans (PGs), consisting of glycosaminoglycans (GAGs) linked with the core protein through a tetrasaccharide linkage region, play roles in many important biological events. The chemical synthesis of PG glycopeptides is extremely challenging. In this work, the enzymes required for synthesis of chondroitin sulfate (CS) PG (CSPG) have been expressed and the suitable sequence of enzymatic reactions has been established. To expedite CSPG synthesis, the peptide acceptor was immobilized on solid phase and the glycan units were directly installed enzymatically onto the peptide. Subsequent enzymatic chain elongation and sulfation led to the successful synthesis of CSPG glycopeptides. The CS dodecasaccharide glycopeptide was the longest homogeneous CS glycopeptide synthesized to date. The enzymatic synthesis was much more efficient than the chemical synthesis of the corresponding CS glycopeptides, which could reduce the total number of synthetic steps by 80 %. The structures of the CS glycopeptides were confirmed by mass spectrometry analysis and NMR studies. In addition, the interactions between the CS glycopeptides and cathepsin G were studied. The sulfation of glycan chain was found to be important for binding with cathepsin G. This efficient chemoenzymatic strategy opens new avenues to investigate the structures and functions of PGs. [ABSTRACT FROM AUTHOR]

Proteoglycans (PGs), consisting of glycosaminoglycans (GAGs) linked with the core protein through a tetrasaccharide linkage region, play roles in many important biological events. The chemical synthesis of PG glycopeptides is extremely challenging. In this work, the enzymes required for synthesis of chondroitin sulfate (CS) PG (CSPG) have been expressed and the suitable sequence of enzymatic reactions has been established. To expedite CSPG synthesis, the peptide acceptor was immobilized on solid phase and the glycan units were directly installed enzymatically onto the peptide. Subsequent enzymatic chain elongation and sulfation led to the successful synthesis of CSPG glycopeptides. The CS dodecasaccharide glycopeptide was the longest homogeneous CS glycopeptide synthesized to date. The enzymatic synthesis was much more efficient than the chemical synthesis of the corresponding CS glycopeptides, which could reduce the total number of synthetic steps by 80 %. The structures of the CS glycopeptides were confirmed by mass spectrometry analysis and NMR studies. In addition, the interactions between the CS glycopeptides and cathepsin G were studied. The sulfation of glycan chain was found to be important for binding with cathepsin G. This efficient chemoenzymatic strategy opens new avenues to investigate the structures and functions of PGs. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels. [ABSTRACT FROM AUTHOR]

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n  = 81) and mouse (n  = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) influence protein functionality by modulating protein stability, localization, and interactions with other molecules, thereby controlling various cellular processes. Common PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, SUMOylation, methylation, sulfation, and nitrosylation. Among these modifications, O-GlcNAcylation has been shown to play a critical role in cancer development and progression, especially in hepatocellular carcinoma (HCC). This review outlines the role of O-GlcNAcylation in the development and progression of HCC. Moreover, we delve into the underlying mechanisms of O-GlcNAcylation in HCC and highlight compounds that target O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) to improve treatment outcomes. Understanding the role of O-GlcNAcylation in HCC will offer insights into potential therapeutic strategies targeting OGT and OGA, which could improve treatment for patients with HCC. [ABSTRACT FROM AUTHOR]

Samarium-cobalt (SmCo) magnets, comprised of rare earth elements (REE), and cobalt (Co) are widely employed in diverse sectors such as aerospace, medical, defense, automotive, and more due to their unique properties such as outstanding high-temperature resistance, superior corrosion resistance, a higher Curie temperature, and high energy density. REE and Co are on the critical metals list for many years, along with increased production costs and challenges. With the increasing amount of waste SmCo, the recycling of these magnets has gained importance. This study investigates the recycling of SmCo magnet scraps through sulfation, selective oxidation, and water leaching. The effect of experimental parameters, such as powder/acid concentration, selective oxidation temperature, selective oxidation time, solid/liquid ratio and leaching time for water leaching are studied in detail. The optimal parameters are determined: 800°C selective oxidation temperature, 1-h selective oxidation time, 1/3 g/ml magnet: acid ratio, 2-h water leaching time and 1/20 water leaching s/l ratio. Under the optimum conditions the extraction efficiency of Sm reached approximately 65%, The solubility of Fe, Co, and Cu metals in the solution is negligible. [ABSTRACT FROM AUTHOR]

Sulfated polysaccharides have a variety of important biologically active properties, such as anticoagulant, hypolipidemic, antiviral activity, the ability to be a means of targeted drug delivery and to improve the water solubility of certain drugs. Initial and sulfated polysaccharides' biological activity depends on the method of their preparation, composition and structure. Currently, there is an extensive body of literature data on methods for the sulfation of various natural polysaccharides. However, modern reviews on this topic mainly focus on the biological activity and application of sulfated polymers, rather than on synthesis methods. The latest comprehensive review on methods for the synthesis of sulfated polysaccharides was performed by Caputo in 2019. To further study this area, you need to know the latest trends in this topic. Based on this, we decided to create a new, up-to-date review covering most of the existing methods for the synthesis of sulfated polysaccharides. This work examined methods for the synthesis of biologically active polysaccharide sulfates and their effect on polymer characteristics, as well as the advantages and disadvantages of each method. Traditional methods for sulfating polysaccharides were reviewed such as using a complex of sulfur trioxide with pyridine, and new methods based on the use of toxic free and corrosive free reagents. Some data on the biological activity of the obtained polysaccharides are considered. [ABSTRACT FROM AUTHOR]

Tyrosine phosphorylation is a crucial posttranslational modification that is involved in various aspects of cell biology and often has functions in cancers. It is necessary not only to identify the specific phosphorylation sites but also to quantify their phosphorylation levels under specific pathophysiological conditions. Because of its high sensitivity and accuracy, mass spectrometry (MS) has been widely used to identify endogenous and synthetic phosphotyrosine proteins/peptides across a range of biological systems. However, phosphotyrosine‐containing proteins occur in extremely low abundance and they degrade easily, severely challenging the application of MS. This review highlights the advances in both quantitative analysis procedures and enrichment approaches to tyrosine phosphorylation before MS analysis and reviews the differences among phosphorylation, sulfation, and nitration of tyrosine residues in proteins. In‐depth insights into tyrosine phosphorylation in a wide variety of biological systems will offer a deep understanding of how signal transduction regulates cellular physiology and the development of tyrosine phosphorylation‐related drugs as cancer therapeutics. [ABSTRACT FROM AUTHOR]

A hierarchically porous sulfated geopolymer catalyst was prepared by three staged sequential treatments involving desilication, ion exchange, and sulfation steps. The first step helped generate hierarchical porosity through the selective removal of Si. The desilicated geopolymer was converted from basic Na-form to acidic H-form through ion exchange with ammonium chloride solution. The ion-exchanged geopolymer was then impregnated with sulfuric acid to produce a super-acidic sulfated geopolymer catalyst. The physicochemical characteristics of the catalyst were analyzed by XRD, FE-SEM, TEM, BET, XPS, NH3-TPD, and FTIR analysis. Three types of model fuels containing pyridine, indole, and carbazole were prepared to evaluate the performance of the catalyst. The influence of parameters affecting the oxidation of pyridine was assessed by conducting the reaction with varying amounts of catalyst, stirring speed, oxidant to nitrogen ratio, temperature, and initial nitrogen concentration. The reaction proceeded via nucleophilic attack by pyridine on the catalyst and followed pseudo first-order kinetics with a TOF and TON of 22.4 h−1 and 134.4, respectively. The oxidized products were removed from the model oil by extraction with aqueous solvents, and the effect of influencing parameters on the extraction efficiency was also studied. The efficiency of the coupled oxidation-extraction process for the three model fuels varied in the order: pyridine > indole > carbazole. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pyrite ore as the only additive is used for sulfation reaction of LiCoO 2. • The mechanism of the sulfation reaction of LiCoO 2 was obtained. • Lithium deintercalation has been verified through density functional theory calculations. • High purity Li 2 CO 3 could be produced from the lithium sulfate leaching solution. Recovery of valuable metals from spent lithium-ion batteries (LIBs) is of great importance for resource sustainability and environmental protection. This study introduced pyrite ore (FeS 2) as an alternative additive to achieve the selective recovery of Li 2 CO 3 from spent LiCoO 2 (LCO) batteries. The mechanism study revealed that the sulfation reaction followed two pathways. During the initial stage (550 °C–800 °C), the decomposition and oxidation of FeS 2 and the subsequent gas–solid reaction between the resulting SO 2 and layered LCO play crucial roles. The sulfation of lithium occurred prior to cobalt, resulting in the disruption of layered structure of LCO and the transformation into tetragonal spinel. In the second stage (over 800 °C), the dominated reactions were the decomposition of orthorhombic cobalt sulfate and its combination with rhombohedral Fe 2 O 3 to form CoFe 2 O 4. The deintercalation of Li from LCO by the substitution of Fe and conversion of Co(III)/Fe(II) into Co 3 O 4 /CoFe 2 O 4 were further confirmed by density functional theory (DFT) calculation results. This fundamental understanding of the sulfation reaction facilitated the future development of lithium extraction methods that utilized additives to substantially reduce energy consumption. [ABSTRACT FROM AUTHOR]

Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer's disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e., N-dearylation (M6), hydroxylation (M1, M19, M21), dihydroxylation (M7, M8, M14, M22), trihydroxylation (M13, M18), hydroxylation and reduction (M20), dihydroxylation and reduction (M9, M16), hydrolysis (M23), hydroxylation and glucuronidation (M11, M15), hydroxylation and sulfation (M17), dihydroxylation and sulfation (M10, M12), N-dearylation and hydroxylation (M3, M4), N-dearylation and dihydroxylation (M5), and N-dearylation and trihydroxylation (M2)] were identified from JP-1366 incubation with the hepatocytes from humans, mice, rats, dogs, and monkeys. Based on the cytochrome P450 (CYP) screening test and immune-inhibition analysis with CYP antibodies, CYP3A4 and CYP3A5 played major roles in the metabolism of JP-1366 to M1, M3, M4, M6, M8, M9, M13, M14, M16, M18, M19, M21, and M22. CYP1A2, 2C8, 2C9, 2C19, and 2D6 played minor roles in the metabolism of JP-1366. UDP-glucuronosyltransferase (UGT) 2B7 and UGT2B17 were responsible for the glucuronidation of M1 to M15. However, JP-1366 and active metabolite M1 were not substrates for drug transporters such as organic cation transporter (OCT) 1/2, organic anion transporter (OAT) 1/3, organic anion transporting polypeptide (OATP)1B1/1B3, multidrug and toxic compound extrusion (MATE)1/2K, P-glycoprotein (P-gp), and breast cancer-resistant protein (BCRP). Only M1 showed substrate specificity for P-gp. The findings indicated that drug-metabolizing enzymes, particularly CYP3A4/3A5, may have a significant role in determining the pharmacokinetics of zastaprazan while drug transporters may only have a small impact on the absorption, distribution, and excretion of this compound. [ABSTRACT FROM AUTHOR]

• Heparan sulfate oligosaccharides selectively inhibit the collagenase activity of cathepsin K. • The inhibition mechanism involves heparan sulfate-induced dimerization of cathepsin K. • Heparan sulfate stabilizes the active conformation of cathepsin K and extents its half-life. • Structurally defined heparan sulfate oligosaccharides inhibit bone resorption without affecting osteoclasts differentiation. Cathepsin K (CtsK) is a cysteine protease with potent collagenase activity. CtsK is highly expressed by bone-resorbing osteoclasts and plays an essential role in resorption of bone matrix. Although CtsK is known to bind heparan sulfate (HS), the structural details of the interaction, and how HS regulates the biological functions of CtsK, remains largely unknown. In this report, we discovered that HS is a multifaceted regulator of the structure and function of CtsK. Structurally, HS forms a highly stable complex with CtsK and induces its dimerization. Co-crystal structures of CtsK with bound HS oligosaccharides reveal the location of the HS binding site and suggest how HS may support dimerization. Functionally, HS plays a dual role in regulating the enzymatic activity of CtsK. While it preserves the peptidase activity of CtsK by stabilizing its active conformation, it inhibits the collagenase activity of CtsK in a sulfation level-dependent manner. These opposing effects can be explained by our finding that the HS binding site is remote from the active site, which allows HS to specifically inhibit the collagenase activity without affecting the peptidase activity. At last, we show that structurally defined HS oligosaccharides effectively block osteoclast resorption of bone in vitro without inhibiting osteoclast differentiation, which suggests that HS-based oligosaccharide might be explored as a new class of selective CtsK inhibitor for many diseases involving exaggerated bone resorption. [ABSTRACT FROM AUTHOR]

Polysaccharides are another important class of bioactive macromolecules in organisms, in addition to proteins and nucleic acids. Numerous studies have confirmed that polysaccharides have various biological activities, including anti‐inflammatory, antiviral, antioxidant, immunomodulatory, anticancer, and other activities, which have attracted the attention of researchers in the biomedical field. In the past decade, increasing researches have found that sulfation modification can improve many physicochemical properties of polysaccharides, significantly enhance their original biological activities, and even generate new activity. Hence, sulfated polysaccharides have attracted more and more attention. A systematic review of the latest research progress and future development prospects of sulfated polysaccharides is very essential to better understand them. Hence, the study has systematically summarized current knowledge about synthesis, structural characteristics, biological activities, and potential molecular mechanisms of sulfated polysaccharides. This review provides some valuable insights and important guidance for the further study of sulfated polysaccharides. [ABSTRACT FROM AUTHOR]

The Beckmann rearrangement of ketoximes to their corresponding amides, using a Brønsted acid-mediated fragmentation and migration sequence, has found wide-spread industrial application. We postulated that the development of a methodology to access ylideneamino sulfates using tributylsulfoammonium betaine (TBSAB) would afford isolable Beckmann-type intermediates and competent partners for subsequent rearrangement cascades. The ylideneamino sulfates generated, isolated as their tributylammonium salts, are sufficiently activated to undergo Beckmann rearrangement without additional reagent activation. The generation of sulfuric acid in situ from the ylideneamino sulfate giving rise to a routine Beckmann rearrangement and additional amide bond cleavage to the corresponding aniline was detrimental to reaction success. The screening of bases revealed inexpensive sodium bicarbonate to be an effective additive to prevent classic Brønsted acid-mediated fragmentation and achieve optimal conversions of up to 99%. [ABSTRACT FROM AUTHOR]

The C(sp2)-aryl sulfonate functional group is found in bioactive molecules, but their synthesis can involve extreme temperatures (>190 °C or flash vacuum pyrolysis) and strongly acidic reaction conditions. Inspired by the 1917 Tyrer industrial process for a sulfa dye that involved an aniline N(sp2)-SO3 intermediate en route to a C(sp2)-SO3 rearranged product, we investigated tributylsulfoammonium betaine (TBSAB) as a milder N-sulfamation to C-sulfonate relay reagent. Initial investigations of a stepwise route involving TBSAB on selected anilines at room temperature enabled the isolation of N(sp2)-sulfamate. Subsequent thermal rearrangement demonstrated the intermediary of a sulfamate en route to the sulfonate; however, it was low-yielding. Investigation of the N-sulfamate to C--sulfonate mechanism through control experiments with variation at the heteroatom positions and kinetic isotope experiments (KIEH/D) confirmed the formation of a key N(sp2)-SO3 intermediate and further confirmed an intermolecular mechanism. Furthermore, compounds without an accessible nitrogen (or oxygen) lone pair did not undergo sulfamation- (or sulfation) -to-sulfonation under these conditions. A one-pot sulfamation and thermal sulfonation reaction was ultimately developed and explored on a range of aniline and heterocyclic scaffolds with high conversions, including N(sp2)-sulfamates (O(sp2)-sulfates) and C(sp2)-sulfonates, in up to 99 and 80% (and 88% for a phenolic example) isolated yield, respectively. Encouragingly, the ability to modulate the ortho-para selectivity of the products obtained was observed under thermal control. A sulfonated analog of the intravenous anesthetic propofol was isolated (88% yield), demonstrating a proof-of-concept modification of a licensed drug alongside a range of nitrogen- and sulfur-containing heterocyclic fragments used in drug discovery. [ABSTRACT FROM AUTHOR]

Posttranslational modifications (PTMs) are covalent modifications of proteins that modulate the structure and functions of proteins and regulate biological processes. The development of various mass spectrometry‐based proteomics workflows has facilitated the identification of hundreds of PTMs and aided the understanding of biological significance in a high throughput manner. Improvements in sample preparation and PTM enrichment techniques, instrumentation for liquid chromatography‐tandem mass spectrometry (LC‐MS/MS), and advanced data analysis tools enhance the specificity and sensitivity of PTM identification. Highly prevalent PTMs like phosphorylation, glycosylation, acetylation, ubiquitinylation, and methylation are extensively studied. However, the functions and impact of less abundant PTMs are not as well understood and underscore the need for analytical methods that aim to characterize these PTMs. This review focuses on the advancement and analytical challenges associated with the characterization of three less common but biologically relevant PTMs, specifically, adenosine diphosphate‐ribosylation, tyrosine sulfation, and tyrosine nitration. The advantages and disadvantages of various enrichment, separation, and MS/MS techniques utilized to identify and localize these PTMs are described. [ABSTRACT FROM AUTHOR]

3'-Phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) deficiency is a rare disorder due to biallelic pathogenic variants in the PAPSS2 gene. This disorder was first described in 1998 by Ahmad et al. and Faiyaz ul Haque et al. To date, 79 patients with PAPSS2 deficiency have been reported. The main reported features of these patients are related to bone abnormalities and clinical/biochemical androgen excess. Disproportionate short stature and symptoms associated with spondylar skeletal dysplasia are the most common clinical features that require clinical attention. Androgen excess has been described much less commonly. This review summarizes the currently published clinical, molecular, and biochemical features of patients with PAPSS2 deficiency. [ABSTRACT FROM AUTHOR]

In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management. [ABSTRACT FROM AUTHOR]

In the current study, two series of catalysts were synthesized and characterized by various physicochemical techniques. In the first series of catalysts, a chemical precipitation method was used for loading 1–20 wt. % ZrO2 on the surface of sugarcane bagasse fly ash (SCBFA) with the goal of finding out the optimal ZrO2 loading. In the second series, the 20% ZrO2/SCBFA composition was modified by (1–10 wt. %) SO42− by wet impregnation method. The acidity of these catalysts was determined through the dehydration of isopropyl alcohol and the chemisorption of pyridine and 2,6-dimethyl pyridine. The catalytic efficiency for the dehydration of methanol to dimethyl ether (DME) in a fixed-bed reactor at atmospheric pressure was investigated. A ~ 95% yield toward DME is maximized over the 10% SO42−/20% ZrO2/SCBFA catalyst at a reaction temperature of 400°C. Additionally, it maintained nearly the same efficiency over a 90-h period and demonstrated outstanding long-term stability. The specific surface area and the acidity are the most important factors responsible for enhancing the catalytic performance in this reaction. Our study reflects that SCBFA-supported zirconia and that modified with SO42− are low-cost, effective, eco-friendly, and recyclable catalysts that are highly suited to apply for production of DME from methanol. [ABSTRACT FROM AUTHOR]

Sulfonation, primarily facilitated by sulfotransferases, plays a crucial role in the detoxification pathways of endogenous substances and xenobiotics, promoting metabolism and elimination. Traditionally, this bioconversion has been attributed to a family of human cytosolic sulfotransferases (hSULTs) known for their high sequence similarity and dependence on 3′-phosphoadenosine 5′-phosphosulfate (PAPS) as a sulfo donor. However, recent studies have revealed the presence of PAPS-dependent sulfotransferases within gut commensals, indicating that the gut microbiome may harbor a diverse array of sulfotransferase enzymes and contribute to detoxification processes via sulfation. In this study, we investigated the prevalence of sulfotransferases in members of the human gut microbiome. Interestingly, we stumbled upon PAPS-independent sulfotransferases, known as aryl-sulfate sulfotransferases (ASSTs). Our bioinformatics analyses revealed that members of the gut microbial genus Sutterella harbor multiple asst genes, possibly encoding multiple ASST enzymes within its members. Fluctuations in the microbes of the genus Sutterella have been associated with various health conditions. For this reason, we characterized 17 different ASSTs from Sutterella wadsworthensis 3_1_45B. Our findings reveal that SwASSTs share similarities with E. coli ASST but also exhibit significant structural variations and sequence diversity. These differences might drive potential functional diversification and likely reflect an evolutionary divergence from their PAPS-dependent counterparts. [ABSTRACT FROM AUTHOR]

This study involved the creation of highly porous PLA scaffolds through the porogen/leaching method, utilizing polyethylene glycol as a porogen with a 75% mass ratio. The outcome achieved a highly interconnected porous structure with a thickness of 25 μm. To activate the scaffold's surface and improve its hydrophilicity, radiofrequency (RF) air plasma treatment was employed. Subsequently, furcellaran subjected to sulfation or carboxymethylation was deposited onto the RF plasma treated surfaces with the intention of improving bioactivity. Surface roughness and water wettability experienced enhancement following the surface modification. The incorporation of sulfate/carboxymethyl group (DS = 0.8; 0.3, respectively) is confirmed by elemental analysis and FT-IR. Successful functionalization of PLA scaffolds was validated by SEM and XPS analysis, showing changes in topography and increases in characteristic elements (N, S, Na) for sulfated (SF) and carboxymethylated (CMF). Cytocompatibility was evaluated by using mouse embryonic fibroblast cells (NIH/3T3). [ABSTRACT FROM AUTHOR]

Histone H3 tyrosine-99 sulfation (H3Y99sulf) is a recently identified histone mark that can cross-talk with H4R3me2a to regulate gene transcription, but its role in cancer biology is less studied. Here, we report that H3Y99sulf is a cancer-associated histone mark that can mediate hepatocellular carcinoma (HCC) cells responding to hypoxia. Hypoxia-stimulated SNAIL pathway elevates the expression of PAPSS2, which serves as a source of adenosine 30-phosphate 50-phos-phosulfate for histone sulfation and results in upregulation of H3Y99sulf. The transcription factor TDRD3 is the downstream effector of H3Y99sulf-H4R3me2a axis in HCC. It reads and co-localizes with the H3Y99sulf-H4R3me2a dual mark in the promoter regions of HIF1A and PDK1 to regulate gene transcription. Depletion of SULT1B1 can effectively reduce the occurrence of H3Y99sulf-H4R3me2a-TDRD3 axis in gene promoter regions and lead to downregulation of targeted gene transcription. Hypoxia-inducible factor 1-alpha and PDK1 are master regulators for hypoxic responses and cancer metabolism. Disruption of the H3Y99sulf-H4R3me2a-TDRD3 axis can inhibit the expression and functions of hypoxia-inducible factor 1-alpha and PDK1, resulting in suppressed proliferation, tumor growth, and survival of HCC cells suffering hypoxia stress. The present study extends the regulatory and functional mechanisms of H3Y99sulf and improves our understanding of its role in cancer biology. [ABSTRACT FROM AUTHOR]