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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]

Copyright of Nonferrous Metals (Extractive Metallurgy) is the property of Beijing Research Institute of Mining & Metallurgy Technology Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

ABSTRACT Posttranslational tyrosine sulfation of peptides and proteins is catalysed by tyrosylprotein sulfotransferases (TPSTs). In Arabidopsis, tyrosine sulfation is essential for the activities of peptide hormones, such as phytosulfokine (PSK) and root meristem growth factor (RGF). Here, we identified a TPST‐encoding gene, MtTPST, from model legume Medicago truncatula. MtTPST expression was detected in all organs, with the highest level in root nodules. A promoter:GUS assay revealed that MtTPST was highly expressed in the root apical meristem, nodule primordium and nodule apical meristem. The loss‐of‐function mutant mttpst exhibited a stunted phenotype with short roots and reduced nodule number and size. Application of both of the sulfated peptides PSK and RGF3 partially restored the defective root length of mttpst. The reduction in symbiotic nodulation in mttpst was partially recovered by treatment with sulfated PSK peptide. MtTPST‐PSK module functions downstream of the Nod factor signalling to promote nodule initiation via regulating accumulation and/or signalling of cytokinin and auxin. Additionally, the small‐nodule phenotype of mttpst, which resulted from decreased apical meristematic activity, was partially complemented by sulfated RGF3 treatment. Together, these results demonstrate that MtTPST, through its substrates PSK, RGF3 and other sulfated peptide(s), positively regulates nodule development and root growth. [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]

To investigate the effect of sulfated modification on the structure and function of coconut haustorium polysaccharide (CHP), three kinds of sulfated coconut haustorium polysaccharides (SCHP-2, SCHP-3, and SCHP-4) were prepared using sulfation reagents containing different ratios of chlorosulfonic acid and pyridine (v/v, mL/mL: 1/2, 1/3, and 1/4) after extracting CHP from the raw materials of coconut haustorium, and their basic chemical compositions, structural characteristics and antioxidant activity in vitro were compared and analyzed. Results showed that all three sulfation reagents were able to modify CHP (characteristic peaks of S=O and C-O-S were observed near 1100~1250 cm−1 and 820 cm−1 in infrared spectra, respectively), and the degree of substitution (DS) was the highest (0.75) at the ratio of chlorosulfonic acid and pyridine for 1/2. The total sugar, uronic acid content, and molecular weight of the three SCHP decreased, and the molar content of monosaccharides also changed when comparing with that of CHP. The thermal stability had slightly weakened as well (the degradation temperature of polysaccharides decreased from 211.17 ℃ and 282.01 ℃ of CHP to 194.86~207.70 ℃ and 233.35~262.46 ℃ of SCHP, respectively). The results of antioxidant experiments in vitro showed that the scavenging activity of SCHP on DPPH and hydroxyl radicals was lower than that of CHP, and the larger the DS was, the more obvious the decrease in activity was. In terms of the ABTS+ radicals scavenging ability and ferrous ions chelating activity, increasing DS could enhance the activity of SCHP. At 8 mg/mL, the ABTS+ radicals scavenging rate (54.82%) and ferrous ions chelating rate (15.59%) of SCHP-2 were significantly (P

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]

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]

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]

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]

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]

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]

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]

In this study, polysaccharides were extracted at a rate of 87.5% ± 1.5% from native dandelion roots, and the dandelion root polysaccharides (DRPs) were then chemically modified to obtain sulfated polysaccharides (SDRPs) with a degree of substitution of 1.49 ± 0.07. The effects of modification conditions, physicochemical characterizations, structural characteristics, antioxidant properties, hypoglycemic activity, and proliferative effects on probiotics of DRP derivatives were further investigated. Results showed that the optimum conditions for sulfation of DRPs included esterification reagents (concentrated sulfuric acid: n-butanol) ratio of 3:1, a reaction temperature of 0 °C, a reaction time of 1.5 h, and the involvement of 0.154 g of ammonium sulfate. The DRPs and SDRPs were composed of six monosaccharides, including mannose, glucosamine, rhamnose, glucose, galactose, and arabinose. Based on infrared spectra, the peaks of the characteristic absorption bands of S=O and C-O-S appeared at 1263 cm−1 and 836 cm−1. Compared with DRPs, SDRPs had a significantly lower relative molecular mass and a three-stranded helical structure. NMR analysis showed that sulfated modification mainly occurred on the hydroxyl group at C6. SDRPs underwent a chemical shift to higher field strength, with their characteristic signal peaking in the region of 1.00–1.62 ppm. Scanning electron microscopy (SEM) analysis indicated that the surface morphology of SDRPs was significantly changed. The structure of SDRPs was finer and more fragmented than DRPs. Compared with DRPs, SDRPs showed better free radical scavenging ability, higher Fe2+chelating ability, and stronger inhibition of α-glucosidase and α-amylase. In addition, SDRPs had an excellent promotional effect on the growth of Lactobacillus plantarum 10665 and Lactobacillus acidophilus. Therefore, this study could provide a theoretical basis for the development and utilization of DRPs. [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]

Cell–cell interactions between fibroblasts and immune cells, like macrophages, are influenced by interaction with the surrounding extracellular matrix during wound healing. In vitro hydrogel models that mimic and modulate these interactions, especially of soluble mediators like cytokines, may allow for a more detailed investigation of immunomodulatory processes. In the present study, a biomimetic extracellular matrix model based on fibrillar 3D collagen I networks with a functionalization with heparin or 6-ON-desulfated heparin, as mimics of naturally occurring heparan sulfate, was developed to modulate cytokine binding effects with the hydrogel matrix. The constitution and microstructure of the collagen I network were found to be stable throughout the 7-day culture period. A coculture study of primary human fibroblasts/myofibroblasts and M-CSF-stimulated macrophages was used to show its applicability to simulate processes of progressed wound healing. The quantification of secreted cytokines (IL-8, IL-10, IL-6, FGF-2) in the cell culture supernatant demonstrated the differential impact of glycosaminoglycan functionalization of the collagen I network. Most prominently, IL-6 and FGF-2 were shown to be regulated by the cell culture condition and network constitution, indicating changes in paracrine and autocrine cell–cell communication of the fibroblast–macrophage coculture. From this perspective, we consider our newly established in vitro hydrogel model suitable for mechanistic coculture analyses of primary human cells to unravel the role of extracellular matrix factors in key events of tissue regeneration and beyond. [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]

Background: Small-secreted peptides are increasingly recognized as a novel class of intracellular signal molecules, playing crucial roles in plant growth and development. However, the precise role and mechanism governed by peptides containing Tyrosine Sulfation (PSY) are still under investigation. Currently, there is a lack of accessible information concerning the PSY gene family in wheat. Results: Therefore, in this investigation, we identified 29 PSY genes in Triticum aestivum, with the aim of unraveling their significance in plant development processes and their response to a variety of stress conditions. Phylogenetic analysis showed that TaPSY genes clustered into five groups. Additionally, an analysis of the gene structure of TaPSYs displayed a conserved evolutionary path. The syntenic relationship demonstrated the 69 orthologous gene pairs in T. dicoccoides, Ae. tauschii, T. turgidum, and H. vulgare, respectively. Furthermore, the Ka/Ks analysis indicated that TaPSY genes have experienced purifying selection during their evolutionary processes. The promoters of TaPSY genes were found to contain numerous CAREs, and these elements are known to perform essential functions in various development processes, phytohormone responses, as well as defense and stress mechanisms. In addition, the identification of potential miRNAs targeting TaPSY genes was followed by an examination of their expression patterns across various tissues. Among the 29 TaPSY genes, twenty miRNAs were discovered to target eighteen of them. Moreover, TaPSY genes displayed a distinct expression across different tissues and stress conditions. Conclusions: Hence, these discoveries offer a significant reference point for forthcoming molecular investigations and hold promise for bolstering wheat yield and stress resilience through targeted genetic enhancements and strategic breeding approaches. Highlights: ➢ Signaling peptides, particularly those with Tyrosine Sulfation (PSY) gene family members, have been extensively researched in Arabidopsis. However, there is scarce information available regarding PSY genes in other crops such as wheat. ➢ In this study, we have identified 29 PSY genes in wheat for the first time, shedding light on their significance in plant development and stress response. ➢ Phylogenetic analysis categorized TaPSY genes into five clusters, exhibiting conserved gene structures and notable purifying selection. ➢ Further, the presence of multiple cis-acting regulatory elements (CAREs) in TaPSY promoters and out of the 29 TaPSY genes, 18 TaPSY genes were targeting by miRNAs highlight their roles in various developmental and stress processes. ➢ These discoveries offer invaluable insights for future molecular investigations aimed at boosting wheat yield and enhancing stress tolerance through targeted genetic improvements. [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]

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]

The sulfation roasting leaching process has been investigated as an alternative method for recovering nickel and cobalt from laterite ore. This process involves converting the nickel and cobalt in the ore into sulfates, which can then be dissolved through water leaching, while the iron remains as an insoluble oxide. However, the presence of other components such as magnesium oxide and silica in the laterite ore may hinder the efficiency of the extraction process. This study aimed to examine the influence of silica and magnesium oxide in three different types of laterite ore on the extraction of nickel and cobalt through the sulfation roasting leaching process. Various characterization techniques, including thermodynamic estimation, X-ray diffraction, and chemical analyses by ICP, were employed to analyze the ores, leached solutions, and solid residues. Phase quantification using the Rietveld method through TOPAZ analysis software was conducted on the original ore, sulfation roasted ore, and solid residue. The findings revealed that the recovery of nickel and cobalt was significantly influenced by the silica and magnesium oxide content in the original ore. The ore with the lowest silica and magnesium oxide content exhibited the highest recovery rates, with nickel recovery reaching 86.3 pct and cobalt recovery reaching 85.7 pct. Conversely, the serpentine-rich ore demonstrated the lowest recovery rates, with nickel recovery at 69.9 pct and cobalt recovery at 68.0 pct. The mechanism of how silica and magnesium oxide affect the extraction of nickel and cobalt by sulfation roasting leaching process was clarified. [ABSTRACT FROM AUTHOR]

Mathematical modeling of columnar leaching is a useful tool for predicting and evaluating the kinetics of copper extraction. One commonly used model for this process is the shrinking core model (SCM). In this study, the aim was to develop a model for column leaching of oxidized copper ore based on the SCM, which incorporates the ore sulfation stage before leaching. In sulfation and leaching laboratory-scale tests, we studied the effect of acid dosage (at 22.8, 34.2, and 45.6 kg/t), humidity (at 90%, 100%, and 110% of the saturation humidity of the mineral), ore granulometry (−3/4″ and −3/8″), and rest time (at 24, 48, 72, and 96 h) on sulfation. We found that the highest sulfation reached 49.7% for both granulometries in studies. In the column tests, the effects of acid dosage (at 34.2, 45.6 kg/t), ore granulometry (−3/4″, −3/8″), and rest time (at 24, 48 h) were studied. When the SCM was applied to these tests, we obtained fit qualities within 63.4% and 74.9%. By incorporating the sulfation factor into the SCM predictions, we observed an average increase in adjustment between 24% and 28%. This method is effective for minerals and operating conditions different from the ones studied. [ABSTRACT FROM AUTHOR]

Human coronaviruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose a serious threat to human life and the global economy. To combat emerging viruses and virus variants, it is essential to develop antivirals with non-specific activities. In this study, we report on the synthesis and antiviral properties of four types of polysulfate-grafted maleimide-based enediyne (EDY) molecules. The sulfates in these EDY molecules are designed to target viruses through non-specific electrostatic interactions, providing extracellular viral targeting ability. Meanwhile, the core EDY generates radical species that disintegrate the viral structure proteins, thereby diminishing the infectivity of coronaviruses. Electron paramagnetic resonance spectroscopy confirmed the radical-generating property of enediynes, while antiviral experiments demonstrated that these enediynes exhibit antiviral activity down to micromolar concentrations, suggesting a promising future for this strategy in developing antiviral drugs. [ABSTRACT FROM AUTHOR]

Abstract Pregnenolone is a key intermediate in the biosynthesis of many steroid hormones and neuroprotective steroids. Sulfotransferase family cytosolic 2B member 1 (SULT2B1a) has been reported to be highly selective to sulfate pregnenolone. This study aimed to clarify the effect of missense single nucleotide polymorphisms (SNPs) of the human SULT2B1 gene on the sulfating activity of coded SULT2B1a allozymes toward Pregnenolone. To investigate the effects of single nucleotide polymorphisms of the SULT2B1 gene on the sulfation of pregnenolone by SULT2B1a allozymes, 13 recombinant SULT2B1a allozymes were generated, expressed, and purified using established procedures. Human SULT2B1a SNPs were identified by a comprehensive database search. 13 SULT2B1a nonsynonymous missense coding SNPs (cSNPs) were selected, and site-directed mutagenesis was used to generate the corresponding cDNAs, packaged in pGEX-2TK expression vector, encoding these 13 SULT2B1a allozymes, which were bacterially expressed in BL21 E. coli cells and purified by glutathione-Sepharose affinity chromatography. Purified SULT2B1a allozymes were analyzed for sulfating activities towards pregnenolone. In comparison with the wild-type SULT2B1a, of the 13 allozymes, 11 showed reduced activity toward pregnenolone at 0.1 µM. Specifically, P134L and R259Q allozymes, reported to be involved in autosomal-recessive congenital ichthyosis, displayed low activity (1–10%) toward pregnenolone. The findings of this study may demonstrate the impact of genetic polymorphism on the sulfation of pregnenolone in individuals with different SULT2B1 genotypes.

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.

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology. 3′-Phosphoadenosine 5′-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the primary enzyme to generate the universal sulfonate donor PAPS. The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli (APC) mutation-promoted colonic carcinogenesis has not been reported. Here, we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages, and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer. Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout (ApcΔgut-HetPapss2Δgut) mice were created, and the phenotypes were compared to the spontaneous intestinal tumorigenesis of ApcΔgut-Het mice. ApcΔgut-HetPapss2Δgut mice were more sensitive to gut tumorigenesis, which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor (FXR)-transducin-like enhancer of split 3 (TLE3) gene regulatory axis. Chondroitin sulfate supplementation in ApcΔgut-HetPapss2Δgut mice alleviated intestinal tumorigenesis. In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids–FXR–TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3’-phosphoadenosine 5’-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3’-phosphoadenosine-5’-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.

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]

• 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]

The negatively charged extracellular matrix plays a vital role in intervertebral disc tissues, providing specific cues for cell maintenance and tissue hydration. Unfortunately, suitable biomimetics for intervertebral disc regeneration are lacking. Here, sulfated alginate was investigated as a 3D culture material due to its similarity to the charged matrix of the intervertebral disc. Precursor solutions of standard alginate, or alginate with 0.1% or 0.2% degrees of sulfation, were mixed with primary human nucleus pulposus cells, cast, and cultured for 14 days. A 0.2% degree of sulfation resulted in significantly decreased cell density and viability after 7 days of culture. Furthermore, a sulfation-dependent decrease in DNA content and metabolic activity was evident after 14 days. Interestingly, no significant differences in cell density and viability were observed between surface and core regions for sulfated alginate, unlike in standard alginate, where the cell number was significantly higher in the core than in the surface region. Due to low cell numbers, phenotypic evaluation was not achieved in sulfated alginate biomaterial. Overall, standard alginate supported human NP cell growth and viability superior to sulfated alginate; however, future research on phenotypic properties is required to decipher the biological properties of sulfated alginate in intervertebral disc cells. [ABSTRACT FROM AUTHOR]