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Antrodia cinnamomea-derived sulfated polysaccharides (Ac-SPSs) have health benefits, but their yield is low. This study explores a strategy to increase Ac-SPS yield and elucidates the biofunctions of Ac-SPS. For this, A. cinnamomea mycelia were treated with zinc sulfate (ZnSO 4 ) administered at 1, 10, and 100 μM. Firstly, functional assay indicated that ZnSO 4 increases the Ac-SPS yield by 20 %-30 % compared with the control treatment. ZnSO 4 engenders a population of middle-molecular-weight (~200 kDa) Ac-SPSs. Ac-SPS (ASZ-10) from A. cinnamomea treated with 10 μM ZnSO 4 exhibits the best anti-proliferation ability against lung cancer A549 cells. Co-treatment of ASZ-10 does not inhibit lipopolysaccharide-induced inflammation but does induce M1-related markers of macrophage RAW264.7 cells. Secondly, immunomodulatory properties showed that ASZ-10 increases the expression of CD80 + and CD86 + in M-CSF-stimulated bone-marrow-derived macrophages. ASZ-10 induces M1 polarization through up-regulation of the AKT/mTOR pathway as confirmed by AKT and mTOR inhibitors eliminating ASZ-10-induced M1-like markers of macrophages. Through systemic chemical and functional analysis, this study shows that trace amounts (10 μM) of ZnSO 4 increase Ac-SPS yield and it reveals that ASZ-10 exhibits anti-cancer activity and acts as a stimulator for M1 macrophages by stimulation of AKT and mTOR., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. Content will be included as a part of Zhi-Hu Lin's doctoral thesis at the Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In connection with our interest in the phytochemical investigation of Elaeocarpus hainanensis Oliv. (Elaeocarpaceae) growing in Vietnam, two new sulphated oleanane triterpenes were obtained herein and structurally identified. Based on the combination of the extensive 1D-, 2D NMR and HR ESI MS spectroscopic data analysis, their chemical structures have been elucidated as 1 α ,3 β -dihydroxy-olean-18-ene 1-sulphate ( 1 ) and 1 α ,3 β -dihydroxy-olean-12-ene 1-sulphate ( 2 ). Notably, compounds 1 and 2 are corroborating the proposition that triterpenoid sulphates serve as chemosystematic markers of the Elaeocarpus genus. Additionally, all these two new compounds 1 and 2 strongly inhibited α -glucosidase in vitro with the respective IC 50 values of 3.81 ± 0.33 µM and 21.27 ± 0.48 µM, which were significantly better than that obtained from positive control, acarbose (IC 50 247.73 ± 11.85 µM).

Nanomaterials, with their small size, surface characteristics, and antibacterial properties, are extensively employed across environmental, energy, biomedical, agricultural, and other industries. This study examined the antibacterial efficacy of magnesium hydroxide (Mg(OH) 2 ) nanoparticles (NPs) against sulfate-reducing bacteria (SRB) within sediments. The inhibitory effects of two types of Mg(OH) 2 NPs with distinct particle sizes (20.3 and 29.6 nm) and concentrations (0-10.0 mg/mL) were examined under optimal treatment conditions. The antibacterial mechanisms of Mg(OH) 2 NPs through direct contact and dissolution effects were determined. The results revealed a correlation between the concentration, particle size, and inhibitory activity, with the smallest NPs (20.3 nm) at the highest concentration (10.0 mg/mL) substantially reducing SRB counts from 8.77 ± 0.18 to 6.48 ± 0.13 log 10 colony forming units/mL after 6 h treatment. Treatment with high concentrations of Mg(OH) 2 NPs induced cellular damage, reduced intracellular lactate dehydrogenase activity, and elevated intracellular catalase activity and H 2 O 2 content, suggesting that the contact effect of NPs stimulated SRB. This leads to oxidative stress response and structural damage to the cell membrane, which has emerged as the primary driver of the antibacterial action of Mg(OH) 2 NPs. This study presents a novel nanomaterial that can inhibit and control SRB in natural sedimentary environments., (© 2024. The Author(s).)

Our previous studies have shown that sulfated Cyclocarya paliurus polysaccharides (SCP3) can alleviate intestinal oxidative stress (OS) damage by improving the antioxidant capacity of the intestine, but its mechanism still needs further exploration. This study aimed to reveal the possible underlying protective mechanism of SCP3 against OS damage of intestinal epithelial cells (IEC-6) based on transcriptome profiling. The results showed that SCP3 could increase the activity of superoxide dismutase and reduce the production of malondialdehyde and reactive oxygen species. In addition, the SCP3 could also alleviate the H 2 O 2 -induced high apoptosis rate and mitochondrial membrane potential decrease in IEC-6 cells. RNA-sequencing results showed that there were 2152 differentially expressed genes between the control group and the SCP3 group, and the mitogen-activated protein kinases (MAPK) and PI3K-Akt signaling pathways are the main signaling pathways that contributed to SCP3 protecting IEC-6 cells from OS damage. In summary, the SCP3 plays a role in improving intestinal cell damage by inhibiting OS, which may be closely related to the PI3K/Akt and MAPK signaling pathways. PRACTICAL APPLICATION: This study provides a theoretical basis for the practical application of Cyclocarya paliurus polysaccharides as an antioxidant ingredient in auxiliary medicines and functional foods., (© 2024 Institute of Food Technologists.)

To develop a reliable sulfide (S 2- ) autotrophic denitrification (SAD) process under S 2- and SO 4 2- salinity stresses, the biofilm performance and microbial mechanisms were comparatively studied using different inocula of activated sludge (AS) and intertidal sediment (IS). Biofilm IS enriched more denitrification genes (0.34 %) and S 2- oxidation genes (0.29 %) than those with AS. Higher denitrification performance was obtained under S 2- (100 mg/L) and SO 4 2- (5-15 g/L Na 2 SO 4 ) stresses, but no significantly differences were observed under levels of 0-200 mg/L S 2- and 30 g/L Na 2 SO 4 . Notably, biofilm samples in SAD systems with IS still had more S 2- oxidation genes at high S 2- levels of 100-200 mg/L and Na 2 SO 4 level of 30 g/L. The key functional genus Thiobacillus accumulated well at 30 g/L Na 2 SO 4 , but was strongly inhibited at 200 mg/L S 2- . The findings were advantage to SAD application under sulfide and salinity stresses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N -acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.

Seaweed polysaccharides, particularly sulfated ones, exhibited potent antiviral activity against a wide variety of enveloped viruses, such as herpes simplex virus and respiratory viruses. Different mechanisms of action were suggested, which may range from preventing infection to intracellular antiviral activity, at different stages of the viral cycle. Herein, we generated two chemically engineered sulfated fucans (C303 and C304) from Cystoseira indica by an amalgamated extraction-sulfation procedure using chlorosulfonic acid-pyridine/N,N-dimethylformamide and sulfur trioxide-pyridine/N,N-dimethylformamide reagents, respectively. These compounds exhibited activity against HSV-1 and RSV with 50 % inhibitory concentration values in the range of 0.75-2.5 μg/mL and low cytotoxicity at concentrations up to 500 μg/mL. The antiviral activities of chemically sulfated fucans (C303 and C304) were higher than the water (C301) and CaCl 2 extracted (C302) polysaccharides. Compound C303 had a (1,3)-linked fucan backbone and was branched. Sulfates were present at positions C-2, C-4, and C-2,4 of Fucp, and C-6 of Galp residues of this polymer. Compound C304 had a comparable structure but with more sulfates at C-4 of Fucp residue. Both C303 and C304 were potent antiviral candidates, acting in a dose-dependent manner on the adsorption and other intracellular stages of HSV-1 and RSV replication, in vitro., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ulcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored., Objective: This work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it., Methods: The effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays., Results: NR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-κB pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR., Conclusion: Our findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Effects of potassium monopersulfate (KMPS) on the nitrification activity, aquacultural water quality and bacterial community structure of sponge biocarriers with pre-cultured biofilm (SBBF) were analysed through shaking flask experiments and L. vannamei aquaculture experiments. Changes in the ammonia oxidation rate (AOR) and nitrite oxidation rate (NOR) of SBBF under six KMPS concentration treatments (0, 1, 2, 3, 4 and 5 mg/L) were studied. The results showed that the AOR and NOR of SBBF treated with high concentrations of KMPS (3, 4 and 5 mg/L) were significantly lower than those of the control group (CK) ( p  < 0.05). However, compared with the first dosing of NH 4 Cl and NaNO 2 , the inhibition of AOR and NOR by KMPS on AOR and NOR was weakened after the second and third dosing times. That is, AOR and NOR can recover partially or completely over time. The L. vannamei aquaculture experiment was performed using four concentrations of KMPS (0, 2, 4 and 8 mg/L). The results showed that with increasing KMPS dosage, the average and peak concentrations of NH 4 + -N and NO 2 - -N in each treatment significantly increased ( P  < 0.05), and the final body weight of shrimp significantly decreased ( P  < 0.05). Furthermore the highest dose (8.0 mg/L) of KMPS reduced the survival rate by 9.33% compared to the CK. High-throughput sequencing analysis of the biofilm structure showed that the relative abundances of Nitrospirota, Nitrosomonas and Nitrococcus, which are related to nitrogen cycling, and beneficial bacteria including Firmicutes and Bacilli decreased with the addition of KMPS ( p  < 0.05).

A novel 8-hydroxy quinoline-derived amide receptor, in conjunction with its Cu (II) and Zn (II) complexes, has been strategically developed to function as remarkably efficient fluorescent receptors with a distinct capability for anion sensing. The comprehensive characterization of the synthesized compounds were achieved through UV-Vis, IR, NMR, and HRMS spectroscopic techniques. Among the Cu (II) and Zn (II) complexes, the latter exhibits superior selectivity for anions, specifically dihydrogen phosphate and hydrogen sulfate, as their tetrabutylammonium salts in a 9:1 acetonitrile-water (v/v) mixture. The Cu (II) complex demonstrates enhanced anion binding compared to the amide ligand, albeit with reduced selectivity. Furthermore, the affinity was evaluated using the Benesi-Hildebrand plot. The binding constants and Limit of Detection (LOD) for both complexes were precisely quantified. The Job plot illustrates a clear 1:1 binding interaction between the metal complexes and the guest anions. Significantly, both metal-complex receptors display a broad spectrum of antibacterial activity, against both gram-positive and gram-negative bacteria. It is worth highlighting that the Zn (II) complexed receptor outperforms the Cu (II) complexed receptor, as evidenced by its considerably lower Minimum Inhibitory Concentration (MIC) value against both bacterial strains., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Salmonella is capable of surviving dehydration within various foods, such as dried fruit. Dried fruit, including apple slices, have been the subject of product recalls due to contamination with Salmonella. A study was conducted to determine the fate of Salmonella on apple slices, following immersion in three antimicrobial solutions (viz., ε-polylysine [epsilon-polylysine or EP], sodium bisulfate [SBS], or peracetic acid [PAA]), and subsequent hot air dehydration. Gala apples were aseptically cored and sliced into 0.4 cm thick rings, bisected, and inoculated with a five-strain composite of desiccation-resistant Salmonella, to a population of 8.28 log CFU/slice. Slices were then immersed for 2 min in various concentrations of antimicrobial solutions, including EP (0.005, 0.02, 0.05, and 0.1%), SBS (0.05, 0.1, 0.2, and 0.3%), PAA (18 or 42 ppm), or varying concentrations of PAA + EP, and then dehydrated at 60°C for 5 h. Salmonella populations in positive control samples (inoculated apple slices washed in sterile water) declined by 2.64 log after drying. In the present study, the inactivation of Salmonella, following EP and SBS treatments, increased with increasing concentrations, with maximum reductions of 3.87 and 6.20 log (with 0.1 and 0.3% of the two compounds, respectively). Based on preliminary studies, EP concentrations greater than 0.1% did not result in lower populations of Salmonella. Pretreatment washes with either 18 or 42 ppm of PAA inactivated Salmonella populations by 4.62 and 5.63 log, respectively, following desiccation. Combining PAA with up to 0.1% EP induced no greater population reductions of Salmonella than washing with PAA alone. The addition of EP to PAA solutions appeared to destabilize PAA concentrations, reducing its biocidal efficacy. These results may provide antimicrobial predrying treatment alternatives to promote the reduction of Salmonella during commercial or consumer hot air drying of apple slices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes, manifesting as foot ulcers and impaired wound healing in patients with diabetes mellitus. To solve this problem, sulfated hyaluronic acid (SHA)/collagen-based nanofibrous biomimetic skins was developed and used to promote the diabetic wound healing and skin remodeling. First, SHA was successfully synthetized using chemical sulfation and incorporated into collagen (COL) matrix for preparing the SHA/COL hybrid nanofiber skins. The polyurethane (PU) was added into those hybrid scaffolds to make up the insufficient mechanical properties of SHA/COL nanofibers, the morphology, surface properties and degradation rate of hybrid nanofibers, as well as cell responses upon the nanofibrous scaffolds were studied to evaluate their potential for skin reconstruction. The results demonstrated that the SHA/COL, SHA/HA/COL hybrid nanofiber skins were stimulatory of cell behaviors, including a high proliferation rate and maintaining normal phenotypes of specific cells. Notably, SHA/COL and SHA/HA/COL hybrid nanofibers exhibited a significantly accelerated wound healing and a high skin remodeling effect in diabetic mice compared with the control group. Overall, SHA/COL-based hybrid scaffolds are promising candidates as biomimetic hybrid nanofiber skin for accelerating diabetic wound healing., Competing Interests: Declaration of competing interest The authors declare no competing conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu 2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu 2+ -induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum , thereby suppressing bacteria growth and biofilm formation in vitro , but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at - 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future., (© 2024. The Author(s).)

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL - 1 ) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC 50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO 3 - )-1→4-α-L-fucp(2,3-SO 3 - )-1→section), SFcup showed a best inhibitory efficacy against AChE with IC 50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study investigated the inactivation of Microcystis aeruginosa using a combined approach involving thermally activated peroxyacetic acid (Heat/PAA) and thermally activated persulfate (Heat/PDS). The Heat/PDS algal inactivation process conforms to first-order reaction kinetics. Both hydroxyl radical (•OH) and sulfate radical (SO 4 - •) significantly impact the disruption of cell integrity, with SO 4 - • assuming a predominant role. PAA appears to activate organic radicals (RO•), hydroxyl (•OH), and a minimal amount of singlet oxygen ( 1 O 2 ). A thorough analysis underscores persulfate's superior ability to disrupt algal cell membranes. Additionally, SO 4 - • can convert small-molecule proteins into aromatic hydrocarbons, accelerating cell lysis. PAA can accelerate cell death by diffusing into the cell membrane and triggering advanced oxidative reactions within the cell. This study validates the effectiveness of the thermally activated persulfate process and the thermally activated peroxyacetic acid as strategies for algae inactivation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure-anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid-pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MDA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs' physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf 2.0 /PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs' size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf 2.0 /PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf 2.0 /PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments., Competing Interests: Declaration of Competing Interest The Authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hydrogels have emerged as a new type of wound dressing materials that involved in different stages of the healing processes. However, most of the existing wound dressings mainly offer a protective and moisturizing layer to prevent cross-infection, while the anti-inflammatory and anti-oxidative properties are frequently induced by extra addition of other bioactive molecules. Here, a novel type of sulfated glyco-functionalized hydrogels for wound dressing was prepared through the hybrid supramolecular co-assembly of carbohydrate segments (FG, FGS and FG3S), fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF), and diphenylalanine-dopamine (FFD). Implanting sulfated carbohydrates can mimic the structure of glycosaminoglycans (GAGs), promoting cell proliferation and migration, along with anti-inflammatory effects. In situ polymerization of FFD introduced a secondary covalent network to the hydrogel, meanwhile, providing anti-oxidation and adhesion properties to wound surfaces. Furthermore, the dynamic supramolecular interactions within the hydrogels also confer self-healing capabilities to the wound dressing materials. In vivo experiments further demonstrated significantly accelerated healing rates with the multifunctional hydrogel FG3S-FFD, indicating high application potential., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yan Zhang reports financial support was provided by National Natural Science Foundation of China. Jinghua Chen reports financial support was provided by National Key R&D Program of China. Yan Zhang reports financial support was provided by Natural Science Foundation of Jiangsu Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mycoplasma pneumoniae , a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.

Five new sulfated arylpyrrole and arylpyrrolone alkaloids, denigrins H-L ( 1 - 5 ), along with two known compounds, dictyodendrin B and denigrin G, were isolated from an extract of a New Zealand Dictyodendrilla c.f. dendyi marine sponge. Denigrins H-L represent the first examples of sulfated denigrins , with denigrins H and I ( 1 - 2 ), as derivatives of denigrin D, containing a pyrrolone core, and denigrins J-L ( 3 - 5 ), as derivatives of denigrin E ( 6 ), containing a pyrrole core. Their structures were elucidated by interpretation of 1D and 2D NMR spectroscopic data, ESI, and HR-ESI-MS spectrometric data, as well as comparison with literature data. Compounds 1-5 , along with six known compounds previously isolated from the same extract, showed minimal cytotoxicity against the HeLa cervical cancer cell line.

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.

Natural substances are strategic candidates for drug development in cancer research. Marine-derived molecules are of special interest due to their wide range of biological activities and sustainable large-scale production. Melanoma is a type of skin cancer that originates from genetic mutations in melanocytes. BRAF, RAS, and NF1 mutations are described as the major melanoma drivers, but approximately 20% of patients lack these mutations and are included in the triple wild-type (tripleWT) classification. Recent advances in targeted therapy directed at driver mutations along with immunotherapy have only partially improved patients' overall survival, and consequently, melanoma remains deadly when in advanced stages. Fucose-containing sulfated polysaccharides (FCSP) are potential candidates to treat melanoma; therefore, we investigated Fucan A, a FCSP from Spatoglossum schröederi brown seaweed, in vitro in human melanoma cell lines presenting different mutations. Up to 72 h Fucan A treatment was not cytotoxic either to normal melanocytes or melanoma cell lines. Interestingly, it was able to impair the tripleWT CHL-1 cell proliferation (57%), comparable to the chemotherapeutic cytotoxic drug cisplatin results, with the advantage of not causing cytotoxicity. Fucan A increased CHL-1 doubling time, an effect attributed to cell cycle arrest. Vascular mimicry, a close related angiogenesis process, was also impaired (73%). Fucan A mode of action could be related to gene expression modulation, in special β-catenin downregulation, a molecule with protagonist roles in important signaling pathways. Taken together, results indicate that Fucan A is a potential anticancer molecule and, therefore, deserves further investigation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herpes simplex viruses (HSVs) have an affinity for heparan sulfate proteoglycans on cell surfaces, which is a determinant for virus entry. Herein, several sulfated galactans that mimic the active domain of the entry receptor were employed to prevent HSV infection. They were produced from Grateloupia indica using chlorosulfonic acid-pyridine (ClSO 3 H.Py)/N,N-dimethylformamide reagent (fraction G-402), SO 3 .Py/DMF reagent (G-403), or by aqueous extraction (G-401). These galactans contained varied molecular masses (33-55 kDa), and sulfate contents (12-20 %), and have different antiviral activities. Especially, the galactan (G-402) generated by using ClSO 3 H.Py/DMF, a novel reagent, exhibited the highest level of antiviral activity (EC 50  = 0.36 μg/mL) compared to G-403 (EC 50  = 15.6 μg/mL) and G-401 (EC 50  = 17.9 μg/mL). This most active sulfated galactan possessed a linear chain containing β-(1 → 3)- and α-(1 → 4)-linked Galp units with sulfate group at the O-2/4/6 and O-2/3/6 positions, respectively. The HSV-1 and HSV-2 strains were specifically inhibited by this novel 33 ± 15 kDa galactan, which also blocked the virus from entering the host cell. These results highlight the significant potential of this sulfated galactan for antiviral research and drug development. Additionally, the reagent used for the effective conversion of galactan hydroxy groups to sulfate during extraction may also be useful for the chemical transformation of other natural products., Competing Interests: Declaration of competing interest There are no competing financial interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fungal sulfated polysaccharides (SPS) have been used in the pharmaceutical industry. In this study, sodium sulfate was employed as an elicitor to induce stress on the mycelia of Antrodia cinnamomea for the biosynthesis of SPS with high sulfate content. Sodium sulfate treatments increased the yield of SPS to 4.46 % and increased the sulfate content to 6.8 mmol/g of SPS. SPS were extracted from A. cinnamomea cultured with 500 mM sodium sulfate; these SPSs are denoted as Na500. Na500 exhibited the highest sulfate content and dose-dependent inhibitory activity against LPS-induced production of macrophage interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β). Mechanistically, Na500 hindered the phosphorylation of transforming growth factor-β receptor II (TGFRII), extracellular signal-regulated kinases (ERK), and protein kinase B (AKT) expression. A purified 7.79 kDa galactoglucan, Na500 F3, augmented the anti-inflammation activity by inhibiting LPS-induced TGFβ release. Additionally, Na500 F3 restrained the LPS-induced phosphorylation of p-38, ERK, AKT, and TGFRII in RAW264.7 cells. Na500 F3 impeded the proliferation of lung cancer H1975 cells by inhibiting the phosphorylation of focal adhesion kinase, ERK, and Slug. The anti-inflammation and anticancer properties of Antrodia SPS contribute to its health benefits, suggesting its utility in functional foods., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Sulfated galactofucan (SWZ-4), which was extracted from Sargassum thunbergii, has recently been reported to show anti-inflammatory and anticancer properties. The present study aimed to evaluate whether SWZ-4 attenuates atherosclerosis in apolipoprotein E-knockout (ApoE-KO) mice by suppressing the inflammatory response through the TLR4/MyD88/NF-κB signaling pathway., Methods: Male ApoE-KO mice were fed with a high-fat diet for 16 weeks and intraperitoneally injected with SWZ-4. RAW246.7 cells were treated with lipopolysaccharide (LPS) and SWZ-4. Atherosclerotic lesions were measured by Sudan IV and oil red O staining. Serum lipid profiles, inflammatory cytokines, and mRNA and protein expression levels were evaluated., Results: SWZ-4 decreased serum TNF-α, IL-6 and IL-1 levels, but did not reduce blood lipid profiles. SWZ-4 downregulated the mRNA and protein expression of TLR4 and MyD88, reduced the phosphorylation of p65, and attenuated atherosclerosis in the ApoE-KO mice (p < 0.01). In LPS-stimulated RAW 264.7 cells, SWZ-4 inhibited proinflammatory cytokine production and the mRNA expression of TLR4, MyD88, and p65 and reduced the protein expression of TLR4 and MyD88 and the phosphorylation of p65 (p < 0.01)., Conclusion: These results suggest that SWZ-4 may exert an anti-inflammatory effect on ApoE-KO atherosclerotic mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway in macrophages and therefore may be a treatment for atherosclerosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ischemic wounds are chronic wounds with poor blood supply that delays wound reconstruction. To accelerate wound healing and promote angiogenesis, adipose-derived stem cells (ADSCs) are ideal seed cells for stem cell-based therapies. Nevertheless, providing a favorable environment for cell proliferation and metabolism poses a substantial challenge. A highly sulfated heparin-like polysaccharide 2-N, 6-O-sulfated chitosan (26SCS)-doped poly(lactic-co-glycolic acid) scaffold (S-PLGA) can be used due to their biocompatibility, mechanical properties, and coagent 26SCS high affinity for growth factors. In this study, a nano-scaffold system, constructed from ADSCs seeded on electrospun fibers of modified PLGA, was designed to promote ischemic wound healing. The S-PLGA nanofiber membrane loaded with adipose stem cells ADSCs@S-PLGA was prepared by a co-culture in vitro , and the adhesion and compatibility of cells on the nano-scaffolds were explored. Scanning electron microscopy was used to observe the growth state and morphological changes of ADSCs after co-culture with PLGA electrospun fibers. The proliferation and apoptosis after co-culture were detected using a Cell Counting Kit-8 kit and flow cytometry, respectively. An ischemic wound model was then established, and we further studied the ability of ADSCs@S-PLGA to promote wound healing and angiogenesis. We successfully established ischemic wounds on the backs of rats and demonstrated that electrospun fibers combined with the biological effects of adipose stem cells effectively promoted wound healing and the growth of microvessels around the ischemic wounds. Phased research results can provide a theoretical and experimental basis for a new method for promoting clinical ischemic wound healing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. In this work, the effect of sulfate-reducing bacteria (SRB) on the corrosion behavior of Q235 carbon steel in groundwater was investigated by electrochemical methods, surface analysis, and biological analysis. The results show that SRB utilizes iron as electron donor to sustain the vital activities of organic carbon-starved groundwater during the 14-day experimental period. The microbial community composition analysis at the genus level demonstrate that the diversity and richness decrease after corrosion, and the dominant SRB species has changed from Desulfovibrio to Desulfosporosinus. Moreover, the impedance of the carbon steel in the presence of biofilm was 1 order of magnitude higher than that of other periods in the electrochemical test, indicating that the biofilm and formed ferrous sulfide layer impeded the occurrence of corrosion. Although the 3D topography indicated that the surface of carbon steel was more uneven and pits were increased in the presence of SRB, the average weight loss (0.0396 ± 0.0050 g) was much higher than that without SRB (0.0139 ± 0.0007 g). These results implied that the growth of SRB makes the corrosion process of Q235 carbon steel more complicated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rheumatoid arthritis (RA) is a chronic autoimmune disease. NSAIDS, cyclophosphamide and glucocorticoid were commonly used to treat RA in clinical application, which long-term administration of these drugs caused serious adverse reactions. Therefore, sulfated hyaluronic acid (sHA) gel (SG) was prepared to firstly treat the RA and avoid the problem of toxic side effect caused by long-term application. In vitro evaluation showed that sHA inhibited the level of reactive oxygen species and TNF-α, IL-1β, and IL-6, and decreased the ratio of macrophage M1/M2 type, which exerted better anti-inflammatory capacity. In vivo studies showed that the injection of SG into the joint cavity of collagen-induced rheumatoid arthritis (CIA) rats could effectively treat joint swelling and reduce the level of inflammatory factors in the serum. Immunofluorescence showed that SG exerted its anti-inflammatory activity by decreasing the ratio of M1/M2 type macrophages in synovial tissue. Cartilage tissue sections showed that SG reduced bone erosion and elevated chondrocyte expression. These results confirmed that sHA is expected to be developed as a drug to treat or relieve RA, which could effectively regulate the level of macrophages in rat RA, alleviate the physiological state of inflammatory over-excitation, and improve its anti-inflammatory and antioxidant capacity., Competing Interests: Declaration of competing interest The author hereby declares that there is no conflict of interest in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, a purified macromolecular sulfate glycosaminoglycan whose structural characterization is similar to chondroitin sulfate from the swim bladder of Aristichthys nobilis, named SBSG, was used to explore the intervention effects on arsenic-induced intestinal epithelial cells (IEC-6) damage. Arsenic exposure led to cell membrane rupture, mitochondrial dysfunction, oxidative damage, and down-regulation of tight junction proteins expression. Treatment with SBSG could alleviate arsenic exposure-induced cell damage by decreasing the extracellular lactate dehydrogenase activity and influencing mitochondrial membrane potential, reactive oxygen species level, malondialdehyde content, and anti-oxidative enzyme activity. On the other hand, SBSG could promote nitric oxide production to achieve potential immunoregulation. The Western blot showed that intervention of SBSG mainly could restrain the activation of the JNK signaling pathway and up-regulate the expression of ZO-1 against arsenic-induced cell damage. This study provides a new perspective for understanding the heavy metal detoxification of SBSG on the intestinal and indicates that SBSG could be used as natural antioxidant resistant to heavy metal toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lappaconitine (LA), a diterpenoid alkaloid extracted from the root of Aconitum sinomontanum Nakai, exhibits broad pharmacological effects, including anti-tumor activity. The inhibitory effect of lappaconitine hydrochloride (LH) on HepG2 and HCT-116 cells and the toxicity of lappaconitine sulfate (LS) on HT-29, A549, and HepG2 cells have been described. But the mechanisms of LA against human cervical cancer HeLa cells still need to be clarified. This study was designed to investigate the effects and molecular mechanisms of lappaconitine sulfate (LS) on the growth inhibition and apoptosis in HeLa cells. The cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2´-deoxyuridine (EdU) assay, respectively. The cell cycle distribution and apoptosis were detected by flow cytometry analysis and 4', 6-diamidino-2-phenylindole (DAPI) staining. The mitochondrial membrane potential (MMP) was determined through the 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimi-dazolyl carbocyanine iodide (JC-1) staining. The cell cycle arrest-, apoptosis-, and the phosphatidylinositol-3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) pathway-related proteins were estimated by western blot analysis. LS markedly reduced the viability and suppressed the proliferation of HeLa cells. LS induced G0/G1 cell cycle arrest through the inhibition of Cyclin D1, p-Rb, and induction of p21 and p53. Furthermore, LS triggered apoptosis through the activation of mitochondrial-mediated pathway based on decrease of Bcl-2/Bax ratio and MMP and activation of caspase-9/7/3. Additionally, LS led to constitutive downregulation of the PI3K/AKT/GSK3β signaling pathway. Collectively, LS inhibited cell proliferation and induced apoptosis through mitochondrial-mediated pathway by suppression of the PI3K/AKT/GSK3β signaling pathway in HeLa cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We assumed that miRNAs might regulate the physiological and biochemical processes in plants through their effects on the redox system and phytohormones. To check this hypothesis, the transcriptome profile of wild-type Arabidopsis and lines with decreased ascorbate (Asc), glutathione (GSH), or salicylate (Sal) levels were compared. GSH deficiency did not influence the miRNA expression, whereas lower levels of Asc and Sal reduced the accumulation of 9 and 44 miRNAs, respectively, but only four miRNAs were upregulated. Bioinformatics analysis revealed that their over-represented target genes are associated with the synthesis of nitrogen-containing and aromatic compounds, nucleic acids, and sulphate assimilation. Among them, the sulphate reduction-related miR395 - ATP-sulfurylase couple was selected to check the assumed modulating role of the light spectrum. A greater induction of the Asc- and Sal-responsive miR395 was observed under sulphur starvation in far-red light compared to white and blue light in wild-type and GSH-deficient Arabidopsis lines. Sal deficiency inhibited the induction of miR395 by sulphur starvation in blue light, whereas Asc deficiency greatly reduced it independently of the spectrum. Interestingly, sulphur starvation decreased only the level of ATP sulfurylase 4 among the miR395 target genes in far-red light. The expression level of ATP sulfurylase 3 was higher in far-red light than in blue light in wild-type and Asc-deficient lines. The results indicate the coordinated control of miRNAs by the redox and hormonal system since 11 miRNAs were affected by both Asc and Sal deficiency. This process can be modulated by light spectrum, as shown for miR395., (© 2023 Scandinavian Plant Physiology Society.)

Neurotoxicity and nephrotoxicity are the major dose-limiting factors for the clinical use of colistin against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to investigate the neurotoxic and nephrotoxic effects of colistin formulated with in-house synthesized sodium deoxycholate sulfate (SDCS) in a mouse model. Male mice C57BL/6 were randomly divided into four groups: control (saline solution), colistin (15 mg/kg/day), colistin:SDCS 1:1, and colistin:SDCS 1:2. In the colistin:SDCS treatment groups, the dosage was 15 mg/kg/day colistin equivalent; all mice were treated for 7 successive days. The thermal tolerance, body weight gain and organ weights were measured. The levels of serum blood urea nitrogen (BUN), creatinine (Cr), superoxide dismutase (SOD), and catalase (CAT) were assessed. Histopathological damages were assessed on mice organ. The colistin:SDCS formulations significantly improved thermal pain response of the mice comparable to the control group. The administration did not impair kidney function as evidence from BUN and Cr results; however, the oxidative stress biomarkers decreased in the colistin and colistin-SDCS treated mice. Several abnormalities were observed in the kidney, liver, spleen, and sciatic nerve tissues following colistin treatment, which indicated evidence of toxicity. The colistin-SDCS formulations were associated with less acute toxicity and fewer nephrotoxic and neurotoxic changes compared with the colistin alone group which indicated that SDCS attenuated colistin nephrotoxicity and neurotoxicity. This study highlights the potential application of colistin formulated with SDCS for safer clinical use against MDR Gram-negative bacteria., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epidemiological studies have implicated copper as one of the key environmental risk factors for the pathogenesis of depression. However, the precise mechanism by which copper contribute to the genesis of depression particularly the involvement of oxidative stress-driven neuroinflammation is yet to be fully investigated. Thus, this study was designed to evaluate the effects of copper sulfate (CuSO 4 ) on depression-like behaviors and the role of oxidative stress and pro-inflammatory cytokines in mice. Forty male Swiss mice were distributed into control and three test groups (n = 10), and were treated orally with distilled water (10 mL/kg) or CuSO 4  (25, 50 and 100 mg/kg) daily for 28 days. Afterwards, the tail suspension, forced swim, and sucrose splash tests were used for the detection of depression-like effects. The animals were then euthanized and the brains were processed for the estimation of biomarkers of oxidative stress and pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6). The histomorphological features and neuronal viability of the prefrontal cortex, hippocampus and striatum were also determined. Mice exposed to CuSO 4 displayed depression-like features when compared with controls. The brain concentrations of malondialdehyde, nitrite and pro-inflammatory cytokines were elevated in CuSO 4 -treated mice. Mice exposed to CuSO 4 also had reduced brain antioxidant status (glutathione, glutathione-s-transferase, total thiols, superoxide-dismutase and catalase), as well as altered histomorphological features, and decreased population of viable neuronal cells. These findings suggest that CuSO 4 increases oxidative stress and pro-inflammatory cytokines to elicit depression-like effects in mice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sulfate radical-based advanced oxidation processes (AOPs) combined biological system was a promising technology for treating antibiotic wastewater. However, how pretreatment influence antibiotic resistance genes (ARGs) propagation remains largely elusive, especially the produced by-products (antibiotic residues and sulfate) are often ignored. Herein, we investigated the effects of zero valent iron/persulfate pretreatment on ARGs in bioreactors treating sulfadiazine wastewater. Results showed absolute and relative abundance of ARGs reduced by 59.8%- 81.9% and 9.1%- 52.9% after pretreatments. The effect of 90-min pretreatment was better than that of the 30-min. The ARGs reduction was due to decreased antibiotic residues and stimulated sulfate assimilation. Reduced antibiotic residues was a major factor in ARGs attenuation, which could suppress oxidative stress, inhibit mobile genetic elements emergence and resistant strains proliferation. The presence of sulfate in influent supplemented microbial sulfur sources and facilitated the in-situ synthesis of antioxidant cysteine through sulfate assimilation, which drove ARGs attenuation by alleviating oxidative stress. This is the first detailed analysis about the regulatory mechanism of how sulfate radical-based AOPs mediate in ARGs attenuation, which is expected to provide theoretical basis for solving concerns about by-products and developing practical methods to hinder ARGs propagation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sulphate-reducing bacteria (SRB) are known to cause severe corrosion of steel structures in various industries, resulting in significant economic and environmental consequences. This review paper critically examines the impact of SRB-induced corrosion on steel, including the formation of SRB biofilms, the effect on different types of steel, and the various models developed to investigate this phenomenon. The role of environmental factors in SRB-induced corrosion, molecular techniques for studying SRBs, and strategies for mitigating corrosion are discussed. Additionally, the sustainability implications of SRB-induced corrosion and the potential use of alternative materials were explored. By examining the current state of knowledge on this topic, this review aims to provide a comprehensive understanding of the impact of SRB-induced corrosion on steel and identify opportunities for further research and development.

Osteoarthritis (OA) is a prevalent degenerative joint condition with no effective disease modifying treatments. In this study, we aimed to address multiple OA hallmarks using a combination of pro-chondrogenic sulfated carboxymethylcellulose (sCMC) and anti-catabolic tissue inhibitor of metalloproteases 3 (Timp3) in relevant disease systems. Firstly, we chemically sulfated carboxymethylcellulose to impart a negative charge and improve the stability of cationic Timp3. The modified sCMC exhibited a molecular weight of 10 kDa and a degree of sulfation of ∼10 %. We further demonstrated that sulfation of CMC confers pro-chondrogenic characteristics. Subsequently, we demonstrated that the combination of sCMC and Timp3 effectively reduced key OA hallmarks, such as matrix degradation, inflammation, and protease expression, in a goat ex vivo OA model compared to individual treatments. We further demonstrated that the anti-OA effect of sCMC and Timp3 is mediated through the suppression of NFκB and JNK activation. To validate the clinical potential and mechanism of action, we conducted experiments on human OA explants. The combination treatment synergistically reduced the expression of MMP13 and NFκB in human OA explants. Overall, sCMC-mediated enhancement of Timp3 efficacy synergistically reduced OA-like traits and demonstrates the potential for OA amelioration., Competing Interests: Declaration of competing interest Two authors (AB and DSK) have a granted Indian patent with a patent number: 420443 for the developed drug combination. The other two authors (NS and PK) declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The effects of sulfate on the zinc (Zn) bioaccumulation characteristics and photophysiological mechanisms of the ornamental plant Hydrocotyle vulgaris were explored using a hydroponic culture under three Zn concentrations (300, 500 and 700mgL-1 ) with (400μmolL-1 ) or without the addition of sulfate. Results showed that: (1) tissue Zn concentrations and total Zn contents increased with increasing hydroponic culture Zn concentrations; and sulfate addition decreased Zn uptake and translocation from roots to shoots; (2) Zn exposure decreased photosynthetic pigment synthesis, while sulfate changed this phenomenon, especially for chlorophyll a under 300mgL-1 Zn treatment; (3) Zn exposure decreased photosynthetic function, while sulfate had positive effects, especially on the photosynthetic rate (Pn ) and stomatal conductance (Gs ); and (4) chlorophyll fluorescence parameters related to light energy capture, transfer and assimilation were generally downregulated under Zn stress, while sulfate had a positive effect on these processes. Furthermore, compared to photosynthetic pigment synthesis and photosynthesis, chlorophyll fluorescence was more responsive, especially under 300mgL-1 Zn treatment with sulfate addition. In general, Zn stress affected photophysiological processes at different levels, while sulfate decreased Zn uptake, translocation, and bioaccumulation and showed a positive function in alleviating Zn stress, ultimately resulting in plant growth promotion. All of these results provide a theoretical reference for combining H. vulgaris with sulfate application in the bioremediation of Zn-contaminated environments at the photophysiological level.

This study aimed to demonstrate the potential benefits of donepezil (DPZ) and vitamin D (Vit D) in combination to counteract the neurodegenerative disorders induced by CuSO 4 intake in experimental rats. Neurodegeneration (Alzheimer-like) was induced in twenty-four male Wistar albino rats by CuSO 4 supplement to drinking water (10 mg/L) for 14 weeks. AD rats were divided into four groups: untreated AD group (Cu-AD) and three treated AD groups; orally treated for 4 weeks with either DPZ (10 mg/kg/day), Vit D (500 IU/kg/day), or DPZ + Vit D starting from the 10th week of CuSO 4 intake. Another six rats were used as normal control (NC) group. The hippocampal tissue content of β-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 and the cortical content of acetylcholine (Ach), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Cognitive function tests (Y-maze) and histopathology studies (hematoxylin and eosin and Congo red stains) and immunohistochemistry for neurofilament. Vit D supplementation alleviated CuSO 4 -induced memory deficits including significant reduction hippocampal BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α and cortical AChE and MDA. Vit D remarkably increased cortical Ach, TAC, and hippocampal Bcl-2. It also improved neurobehavioral and histological abnormalities. The effects attained by Vit D treatment were better than those attained by DPZ. Furthermore, Vit D boosted the therapeutic potential of DPZ in almost all AD associated behavioral and pathological changes. Vit D is suggested as a potential therapy to retard neurodegeneration., (© 2023. The Author(s).)

Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. STATEMENT OF SIGNIFICANCE: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The dietary supplementation of red seaweed-derived polysaccharides has been shown to be beneficial to fish and shellfish aquaculture. However, the function of red seaweed (Gracilaria lemaneiformis)-extracted polysaccharide (GLP) on the health status of rabbitfish (Siganus canaliculatus) is still unknown. This study explored the influences of GLP on growth performance, antioxidant activity, and immunity of rabbitfish. Herein, the fish were fed commercial pelleted feed incorporated with the diverse amount of GLP: 0 (control), 0.10 (GLP0.10), and 0.15 g kg -1  (GLP0.15) for 60 days. The results demonstrated that dietary GLP0.15 significantly elevated FBW and WG, while feed utilization efficiency improved (reduced feed conversion ratio and increased protein efficiency ratio) upon GLP0.10 treatment, regarding the control (P < 0.05). Also, dietary administration of GLP0.15 suggestively improved the serum acid phosphatase and lysozyme activity as well as hepatic total antioxidant capacity, catalase, and superoxide dismutase activity. In contrast, GLP0.15decreased the serum alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and malonaldehyde activity when compared to the control (P<0.05). Moreover, the lipase (36.08 and 16.46 U/mgprot in GLP0.10 and GLP0.15, respectively) and amylase (0.43 and 0.23 U/mgprot in GLP0.10 and GLP0.15, respectively) activity recorded the maximum values than the control (8.61 and 0.13 U/mgprot, respectively).Further, the intestinal morphometry was developed (such as increased villus length, width, and area) in the fish fed with a GLP-supplemented diet compared to the control. The KEGG pathway analysis unveiled that several differentially expressed genes (DEGs) in control vs. GLP0.10 and control vs. GLP0.15 were associated with metabolic or immune-associated pathways like antigen processing and presentation, phagosome, complement and coagulation cascades, and platelet activation. The DEGs, namely C3, f5, fgb, MHC1, and cfb, were evaluated in control vs. GLP0.10 and C3 and MHC1 in control vs. GLP0.15, suggesting their possible contributions to GLP-regulated immunity. Additionally, the cumulative mortality of rabbitfish after the Vibrio parahaemolyticus challenge was lower in both GLP0.10 (8.88%) and GLP0.15 (11.11%) than in control (33.33%) (P<0.05). Thus, these findings direct the potential use of GLP as an immunostimulant and growth promoter in rabbitfish aquaculture., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Copper is widely used in agriculture and aquaculture due to its high disinfection properties and relatively low cost. However, the increase in copper concentration due to evaporation can lead to water reservoir pollution, which can harm the health of consumers. The present study aimed to determine the role of sulfated polysaccharides (SPs) extracted from Sargassum tenerimum algae in reducing lesions caused by the heavy metal copper. Zebrafish (Danio rerio) were used as a human model in five treatments. The negative and positive control groups were fed a diet containing zero percent of SPs, while the experimental groups were fed 0.5%, 1%, and 1.5% of SPs in three treatments for 56 days, finally CuSO 4 was exposed only to the positive control group and the groups fed with SPs. Results showed a significant decrease in the activity level of ALT enzymes (39-16 U/mL), AST (67-46 U/mL), and ALP (485-237 U/mL), confirming the results obtained from histopathological studies in CuSO 4 exposed groups. The addition of SPs to the diet resulted in a significant reduction (sig < 0.05) of mortalities due to the decrease of tissue damage. Additionally, due to the anti-inflammatory properties and the protective effect of SPs, a significant decrease (sig < 0.05) was observed in the relative expression of Il-1β and Tnf-α genes., (© 2023. The Author(s).)

Corneal scarring caused by epithelial-stromal injury impairs corneal transparency and visual acuity. Excess secretion of transforming growth factor-beta 1 (TGF-β1), which promotes wound closure, penetrates the corneal stroma via defects in the epithelial basement membrane and induces the differentiation of corneal fibroblasts to myofibroblasts, leading to scar formation. Modulating TGF-β1 penetration might alleviate corneal scar formation and restore transparency. In this study, sulfated hyaluronan (sHA) coatings were self-assembled above wounded corneal stroma to modulate TGF-β1 penetration, and their ability to alleviate corneal scarring was investigated. The formation of sHA coatings was rapid (within 30 s), and the high-sulfated hyaluronan coating efficiently blocked penetration by TGF-β1 and reduced the concentration of TGF-β1 in the corneal stroma. Further investigation showed that the ability of TGF-β1 to induce differentiation of corneal fibroblasts into myofibroblasts was inhibited by sHA binding. Evaluation of corneal scarring with sHA coating in a rabbit model of lamellar resection indicated that a sHA (high sulfation) coating effectively reduced scar formation. Immunohistochemical staining of α-smooth muscle actin and optical coherence tomography of the anterior segment showed minimal scar tissue formation in the sHA group. This work presents a promising alternative to alleviate scarring in corneal epithelial-stromal injury.

Blocking of nutrient uptake and amino acid biosynthesis are considered potential targets for next-generation antifungal drugs against pathogenic fungi, including Cryptococcus neoformans. In this regard, the sulfate assimilation pathway is particularly attractive, as it is only present in eukaryotes such as plants and fungi, yet not in mammals. Here, we demonstrated that the adenylyl sulfate kinase (Met14) in the sulfate assimilation pathway is not essential yet is required for the viability of C. neoformans due to its involvement in biosynthesis of two sulfur-containing amino acids, cysteine and methionine. Met14-dependent cysteine and methionine biosynthesis was found to significantly contribute to a diverse range of pathobiological processes in C. neoformans. Met14-dependent cysteine rather than methionine biosynthesis was also found to play pivotal roles in cell growth and tolerance to environmental stresses and antifungal drugs. In contrast, the Met14-dependent methionine biosynthesis was found to be more important than cysteine biosynthesis for the production of major cryptococcal virulence factors of melanin pigments and polysaccharide capsules. Finally, we also found that despite its attenuated virulence in an insect model, Galleria mellonella, the met14 Δ mutant yielded no difference in virulence in a murine model of systemic cryptococcosis. Hence, clinical inhibition of Met14-dependent amino acid biosynthetic pathways may not be advantageous for the treatment of systemic cryptococcosis. IMPORTANCE Current antifungal drugs have several limitations, such as drug resistance, severe side effects, and a narrow spectrum. Therefore, novel antifungal targets are urgently needed. To this end, fungal sulfur amino acid biosynthetic pathways are considered potential targets for development of new antifungal agents. Here, we demonstrated that Met14 in the sulfate assimilation pathway promotes growth, stress response, and virulence factor production in C. neoformans via synthesis of sulfur-containing amino acids methionine and cysteine. Met14-dependent cysteine rather than methionine synthesis was found to be critical for growth and stress responses, whereas Met14-dependent methionine synthesis was more important for the production of antiphagocytic capsules and antioxidant melanin in C. neoformans. Surprisingly, deletion of the MET14 gene was found to attenuate cryptococcal virulence in an insect model, yet not in a murine model. Collectively, our results showed that Met14-dependent cysteine and methionine biosynthesis play roles that are distinct from each other in C. neoformans. Moreover, Met14 is unlikely to be a suitable anticryptococcal drug target., Competing Interests: The authors declare no conflict of interest.

Background: Calcific aortic stenosis (CAS) is more prevalent, occurs earlier, progresses faster and has worse outcomes in patients with chronic kidney disease (CKD). The uremic toxin indoxyl sulfate (IS) is powerful predictor of cardiovascular mortality in these patients and a strong promoter of ectopic calcification whose role in CAS remains poorly studied. The objective of this study was to evaluate whether IS influences the mineralization of primary human valvular interstitial cells (hVICs) from the aortic valve., Methods: Primary hVICs were exposed to increasing concentrations of IS in osteogenic medium (OM). The hVICs' osteogenic transition was monitored by qRT-PCRs for BMP2 and RUNX2 mRNA. Cell mineralization was assayed using the o-cresolphthalein complexone method. Inflammation was assessed by monitoring NF-κB activation using Western blots as well as IL-1β, IL-6 and TNF-α secretion by ELISAs. Small interfering RNA (siRNA) approaches enabled us to determine which signaling pathways were involved., Results: Indoxyl-sulfate increased OM-induced hVICs osteogenic transition and calcification in a concentration-dependent manner. This effect was blocked by silencing the receptor for IS (the aryl hydrocarbon receptor, AhR). Exposure to IS promoted p65 phosphorylation, the blockade of which inhibited IS-induced mineralization. Exposure to IS promoted IL-6 secretion by hVICs, a phenomenon blocked by silencing AhR or p65. Incubation with an anti-IL-6 antibody neutralized IS's pro-calcific effects., Conclusion: IS promotes hVIC mineralization through AhR-dependent activation of the NF-κB pathway and the subsequent release of IL-6. Further research should seek to determine whether targeting inflammatory pathways can reduce the onset and progression of CKD-related CAS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sulfated polysaccharides (Ac-SPSs) of Antrodia cinnamomea present anti-cancer activity. However, the anti-cancer mechanism of Ac-SPSs is not fully understood and remains largely unexplored. In this study, we identify an Ac-SPS with 7.9 kDa, noted ZnF3, and aim to examine the dual anti-cancer functions of ZnF3 on inhibiting cancer cells and activating macrophages. A biological study shows that ZnF3 inhibits lung cancer cells by inducing subG1 population and apoptosis. ZnF3 downregulates the expression of TGFβ receptor in lung cancer cells. In parallel, ZnF3 activates macrophages via induction of TNF-α and IL-6 secretion, NO production and phagocytosis. ZnF3 activates AKT/mTOR pathway and induces M1 type macrophage polarization. Cancer cells co-cultured with ZnF3-stimulated macrophages, leading to inhibition of lung cancer cells. This study demonstrates that ZnF3 not only directly inhibits cancer cells but also activates macrophages-mediated cytotoxic effect on cancer cells. Moreover, ZnF3 may be a supplement for suppressing lung cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sulfated polysaccharides from sea cucumber Stichopus japonicus (SCSPsj) have been found to modulate the gut microbiota by promoting the growth of probiotics. However, the effects of the combination of SCSPsj and probiotics are still less known. Thus, the present study aimed to investigate the effects of SCSPsj and Lactobacillus gasseri on gut microbiota-altered mice through gut microbiota and metabolomics analysis. In the present study, supplementation with SCSPsj, L. gasseri or the combination of SCSPsj and L. gasseri could effectively ameliorate the body weight gain and fat accumulation in gut microbiota-altered mice treated with low-dose penicillin. The better effect of the combination of SCSPsj and L. gasseri is attributed to the synergistic effect of SCSPsj and L. gasseri . 16S rRNA sequencing revealed that the combination of SCSPsj and L. gasseri can synergistically improve gut microbiota dysbiosis by increasing Lactobacillus and reducing Coriobacteriaceae&#95;UCG-002 . Furthermore, metabolomics results revealed that the combination of SCSPsj and L. gasseri can alleviate metabolic disorders by reducing the levels of lipid and lipid-like molecules in the serum samples, such as trans -vaccenic acid and 3β-hydroxy-5-cholestene. Our findings have proved that the combination of SCSPsj and L. gasseri can benefit host health attributed to the synergistic effect, which is conducive to further application in functional food.