Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Hepatic transcriptomic assessment of Sprague Dawley rats in response to dietary perfluorobutane sulfonate (PFBS) ingestion.

Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats.

Bis(8-hy-droxy-quinolinium) naphthalene-1,5-di-sulfonate tetra-hydrate.

The inter-action between 8-hy-droxy-quinoline (8HQ, C9H7NO) and naphthalene-1,5-di-sulfonic acid (H2NDS, C10H8O6S2) in aqueous media results in the formation of the salt hydrate bis-(8-hy-droxy-quinolinium) naphthalene-1,5-di-sulfonate tetra-hydrate, 2C9H8NO+·C10H6O6S2 2-·4H2O. The asymmetric unit comprises one protonated 8HQ+ cation, half of an NDS2- dianion symmetrically disposed around a center of inversion, and two water mol-ecules. Within the crystal structure, these components are organized into chains along the [010] and [10] directions through O-H⋯O and N-H⋯O hydrogen-bonding inter-actions, forming a di-periodic network parallel to (101). Additional stabilizing inter-actions such as C-H⋯O, C-H⋯π, and π-π inter-actions extend this arrangement into a tri-periodic network structure.

Use of Fludrocortisone for Hyperkalemia in Chronic Kidney Disease Not Yet on Dialysis.

Background: Hyperkalemia is a frequent and potentially lethal complication of chronic kidney disease (CKD). We retrospectively examined the potassium-lowering effect of oral fludrocortisone and its adverse effects in hyperkalemic CKD patients not yet on dialysis. Methods: Thirty-three patients (23 men and 10 women, ages 69±14 years) were included. To control hyperkalemia at the outpatient clinic, twenty-one patients (Group 1) received fludrocortisone (0.05-0.1 mg/day) without changes in angiotensin II receptor blockers (ARBs) and calcium polystyrene sulfonate (CPS), while twelve patients (Group 2) were treated with fludrocortisone in addition to stopping ARBs and/or adding low-dose CPS. Results: Fludrocortisone was administered for a median of 169 days (interquartile range, 47-445). At the first follow-up after fludrocortisone administration, serum potassium dropped from 6.14±0.32 mEq/L to 4.52±1.06 mEq/L (p<0.001) in Group 1 and from 6.37±0.35 mEq/L to 4.08±0.74 mEq/L (p<0.01) in Group 2. Ten patients in Group 1 and five patients in Group 2 measured serum potassium levels at four outpatient visits before and after fludrocortisone administration, respectively. The frequency of serum potassium ≥6.0 mEq/L decreased from 19/40 (48%) to 2/40 (5%) (p<0.001) in Group 1 and from 11/20 (55%) to 0/20 (0%) (p<0.001) in Group 2. Eleven patients experienced sodium retention-related problems after fludrocortisone administration: 7 with worsening leg edema, 2 with pleural effusions, and 2 with pulmonary edema. Conclusion: In pre-dialysis CKD patients, fludrocortisone at low doses effectively reduced serum potassium levels; however, sodium retention was a common adverse effect.

The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

Polystyrene sulfonate resin as an ophthalmic carrier for enhanced bioavailability of ligustrazine phosphate controlled release system.

Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 µm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.

Synthesis of N-isonicotinic sulfonate chitosan and its antibiofilm activity against E. coli and S.aureus.

N-(sodium 2-hydroxypropylsulfonate) chitosan (HSCS), N-sulfonate chitosan (SCS) and N-isonicotinic sulfonate chitosan (ISCS) were prepared. The structures of the prepared chitosan derivatives were characterized by nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and elemental analysis (EA). Antibacterial and antibiofilm activities of these chitosan derivatives were evaluated in vitro. The minimum inhibitory concentration (MIC) of HSCS and SCS against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were 0.625 mg/mL and 0.156 mg/mL, respectively. ISCS exhibited MIC values of 0.313 mg/mL and 0.078 mg/mL against E. coli and S. aureus, respectively. ISCS demonstrated superior antibacterial and antibiofilm properties compared to SCS and HSCS. These findings suggest that the incorporation of a pyridine structure into sulfonate chitosan enhances its antibacterial and antibiofilm activities, and the prepared ISCS has a promising application prospect for controlling the reproduction of microorganisms in the field of food packaging.

Exacerbated interfacial impacts of nanoplastics and 6:2 chlorinated polyfluorinated ether sulfonate by natural organic matter in adult zebrafish: Evidence through histopathology, gut microbiota, and transcriptomic analysis.

Nanoplastics (NPs) interact with cooccurring chemicals and natural organic matter (NOM) in the environment, forming complexes that can change their bioavailability and interfacial toxicity in aquatic organisms. This study aims to elucidate the single and combined impacts of 21-day chronic exposure to low levels of polystyrene NPs (size 80 nm) at 1 mg/L and 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES or F53B) at 200 µg/L in the presence and absence of NOM (humic acid-HA and bovine serum albumin-BSA at 10 mg/L) in adult zebrafish (Danio rerio). Our findings through multiple bioassays, revealed that the mixture group (M), comprising of NPs, F53B, HA, and BSA, caused a higher level of toxicity compared to the single NPs (AN), single F53B (AF), and combined NPs+F53B (ANF) groups. The mixture exposure caused the highest level of vacuolization and nuclear condensation in hepatocytes, and most of the intestinal villi were fused and highly reduced in villi length and crypt depth. Further, the T-AOC levels were significantly lower (p < 0.05), while the MDA levels in the liver and intestine were significantly higher (p < 0.05) in the M group with downregulation of nfkbiaa, while upregulation of prkcda, csf1ra, and il1b apoptosis genes in the liver. Pairwise comparison of gut microbiota showed significantly higher (p < 0.05) abundances of various genera in the M group, including Gordonia, Methylobacterium, Tundrisphaera, GKS98, Pedomicrobium, Clostridium, Candidatus and Anaerobacillus, as well as higher abundance of genera including pathogenic strains, while control group showed higher abundance of probiotic genus ZOR0006 than exposed group (p < 0.01). The transcriptomic analysis revealed highest number of DEGs in the M group (2815), followed by the AN group (506) and ANF group (206) with the activation of relaxin signaling pathway-RSP (slc9a1, slc9a2) and AMP-activated protein kinase (AMPK) pathway (plin1), and suppression of the toll-like receptor (TLR) pathway (tlr4a, tlr2, tlr1), cytokine-cytokine receptor interaction (CCRI) pathway (tnfb, il21r1, il21, ifng1), and peroxisome proliferator-activated receptors (PPAR) pathway (pfkfb3). Overall, toxicity in the M group was higher, indicating that the HA and BSA elevated the interfacial impacts of NPs and F53B in adult zebrafish after chronic environmentally relevant exposure, implying the revisitation of the critical interaction of NOM with co-occurring chemicals and associated impacts.

Single-cell transcriptomics reveal the microenvironment landscape of perfluorooctane sulfonate-induced liver injury in female mice.

Epidemic and animal studies have reported that perfluoroalkyl and polyfluoroalkyl substances (PFASs) are strongly associated with liver injury; however, to date, the effects of PFASs on the hepatic microenvironment remain largely unknown. In this study, we established perfluorooctane sulfonic acid (PFOS)-induced liver injury models by providing male and female C57BL/6 mice with water containing PFOS at varying doses for 4 weeks. Hematoxylin and eosin staining revealed that PFOS induced liver injury in both sexes. Elevated levels of serum aminotransferases including those of alanine aminotransferase and aspartate transaminase were detected in the serum of mice treated with PFOS. Female mice exhibited more severe liver injury than male mice. We collected the livers from female mice and performed single-cell RNA sequencing. In total, 36,529 cells were included and grouped into 10 major cell types: B cells, granulocytes, T cells, NK cells, monocytes, dendritic cells, macrophages, endothelial cells, fibroblasts, and hepatocytes. Osteoclast differentiation was upregulated and the T cell receptor signaling pathway was significantly downregulated in PFOS-treated livers. Further analyses revealed that among immune cell clusters in PFOS-treated livers, Tcf7+CD4+T cells were predominantly downregulated, whereas conventional dendritic cells and macrophages were upregulated. Among the fibroblast subpopulations, hepatic stellate cells were significantly enriched in PFOS-treated female mice. CellphoneDB analysis suggested that fibroblasts interact closely with endothelial cells. The major ligand-receptor pairs between fibroblasts and endothelial cells in PFOS-treated livers were Dpp4_Cxcl12, Ackr3_Cxcl12, and Flt1_complex_Vegfa. These genes are associated with directing cell migration and angiogenesis. Our study provides a general framework for understanding the microenvironment in the livers of female mice exposed to PFOS at the single-cell level.

Next generation risk assessment for occupational chemical safety - A real world example with sodium-2-hydroxyethane sulfonate.

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 µM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a "last resort" e.g. under EU REACH.

The VDAC1 oligomerization regulated by ATP5B leads to the NLRP3 inflammasome activation in the liver cells under PFOS exposure.

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.

Quorum sensing mediated response mechanism of anammox consortia to anionic surfactant: Molecular simulation and molecular evidence.

The widespread use of surfactants raise challenges to biological wastewater treatment. Anaerobic ammonium oxidation (anammox) process has the potential to treat wastewater containing anionic surfactants, but the response of anammox consortia at the molecular level under long-term exposure is unclear. Using high-throughput sequencing and gene quantification, combined with molecular docking, the effect of sodium dodecyl sulfonate (SDS) on anammox consortia were investigated. Levels of reactive oxygen species (ROS) might be lower than the threshold of oxidative damage, while the increase of lactate dehydrogenase (LDH) represented the cell membrane damage. Decreased abundance of functional genes (hdh, hzsA and nirS) indicated the decrease of the anammox bacterial abundance. Trace amounts of N-acyl homoserine lactone (AHL, C6-HSL, C8-HSL and C12-HSL) contained in influent could induce endogenous quorum sensing (QS), which could regulate the correlation between functional bacteria to optimize the microbial community and strengthen the resistance of anammox consortia to SDS. In addition, the proliferation of disinfectant resistance genes might increase the environmental pathogenicity of sewage discharge. This work highlights the potential response mechanism of anammox consortium to surfactants and provides a universal microbial-friendly bioenhancement strategy based on QS.

Highly sulfonated poly ether ether ketone chelated with Cu2+ as a proton exchange membrane at sub-zero temperatures.

Improving the proton conductivity (σ) of proton exchange membranes at low temperatures is very important for expanding their application areas. Here, sulfonated poly ether ether ketone (SPEEK) membranes were prepared with different sulfonation degrees, and its maximum ion exchange capacity is 3.15 mmol/g for 10 h at 60 °C. Highly sulfonated SPEEK membrane exhibits ultra-high water uptake and excellent proton conductivity of 0.074 S/cm at -25 °C due to its abundant -SO3H. Nevertheless, its high swelling ratio and low mechanical strength are not conducive to the practical application of the membrane. Luckily, by employing the chelation of Cu2+ with -SO3- on the SPEEK chain, Cu2+-coordinated SPEEK membranes were prepared, and they not only retain high -SO3H content but also possess robust mechanical properties and good dimensional stability compared to pristine SPEEK membrane. Meanwhile, the σ of the SPEEK-Cu membrane reaches 0.054 S/cm at -25 °C, and its fuel cell maximum power (Wmax) reaches 0.42 W/cm2 at -10 °C, demonstrating superior low-temperature performance in comparison to other reported materials. Particularly, water states in the prepared membranes are quantified by low-temperature differential scanning calorimetry. Because much more water bound to the plentiful -SO3H and Cu2+ inside the membrane endows it with anti-freezing performance, the decay of the σ and the Wmax for the SPEEK-Cu membrane is retarded at sub-zero temperatures. It is envisioned that composite membranes comprising metal ions such as Cu2+-SPEEK have a high potential for sub-zero fuel cell applications.

Perfluorooctane sulfonate promotes the migration of colorectal cancer cells by inducing epithelial-mesenchymal transition.

The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.

Enhanced ophthalmic bioavailability and stability of atropine sulfate via sustained release particles using polystyrene sulfonate resin.

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.

Enhanced Microstructural Uniformity in Sulfuric-Acid-Treated Poly(3,4-Ethylenedioxythiophene):Poly(Styrene Sulfonate) Films Using Raman Map Analysis.

Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films have emerged as potential alternatives to indium-tin oxide as transparent electrodes in optoelectronic devices because of their superior transparency, flexibility, and chemical doping stability. However, pristine PEDOT:PSS films show low conductivities because the insulating PSS-rich domains isolate the conductive PEDOT-rich domains. In this study, the conductivities and corresponding spatially resolved Raman properties of PEDOT:PSS thin films treated with various concentrations of H2SO4 are presented. After the PEDOT:PSS films are treated with the H2SO4 solutions, their electrical conductivities are significantly improved from 0.5 (nontreated) to 4358 S cm-1 (100% v/v). Raman heat maps of the peak shifts and widths of the Cα═Cß stretching mode are constructed. A blueshift and width decrease of the Cα═Cß Raman mode in PEDOT are uniformly observed in the entire measurement area (20 × 20 µm2), indicating that microstructural transitions are successfully accomplished across the area from the coiled to linear conformation and high crystallinity upon H2SO4 treatment. Thus, it is proved that comprehensive Raman map analysis can be easily utilized to clarify microstructural properties distributed in large areas induced by various dopants. These results also offer valuable insights for evaluating and optimizing the performance of other conductive thin films.

Perfluorooctane sulfonate induces ferroptosis-dependent non-alcoholic steatohepatitis via autophagy-MCU-caused mitochondrial calcium overload and MCU-ACSL4 interaction.

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

Enhancing Optical and Thermal Stability of Blue-Emitting Perovskite Nanocrystals through Surface Passivation with Sulfonate or Sulfonic Acid Ligands.

This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or sulfonic acid) ligands. Four different phenylated ligands, including sodium ß-styrenesulfonate (SbSS), sodium benzenesulfonate (SBS), sodium p-toluenesulfonate (SPTS), and 4-dodecylbenzenesulfonic acid (DBSA), were employed to modify blue-emitting CsPbBr1.5Cl1.5 perovskite NCs, resulting in improved size uniformity and surface functionalization. Transmission electron microscopy and X-ray photoelectron spectroscopy confirmed the successful anchoring of sulfonate or sulfonic acid ligands on the surface of perovskite NCs. Moreover, the photoluminescence quantum yield increased from 32% of the original perovskite NCs to 63% of the SPTS-modified ones due to effective surface passivation. Time-resolved photoluminescence decay measurements revealed extended PL lifetimes for ligand-modified NCs, indicative of reduced nonradiative recombination. Thermal stability studies demonstrated that the SPTS-modified NCs retained nearly 80% of the initial PL intensity when heated at 60 °C for 10 min, surpassing the performance of the original NCs. These findings emphasize the optical and thermal stability enhancement of cesium-based perovskite NCs through surface passivation with suitable sulfonate ligands.

UDP-glycosyltransferase UGT96C10 functions as a novel detoxification factor for conjugating the activated dinitrotoluene sulfonate in switchgrass.

Dinitrotoluene sulfonates (DNTSes) are highly toxic hazards regulated by the Resource Conservation and Recovery Act (RCRA) in the United States. The trinitrotoluene (TNT) red water formed during the TNT purification process consists mainly of DNTSes. Certain plants, including switchgrass, reed and alfalfa, can detoxify low concentrations of DNTS in TNT red water-contaminated soils. However, the precise mechanism by which these plants detoxify DNTS remains unknown. In order to aid in the development of phytoremediation resources with high DNTS removal rates, we identified and characterized 1-hydroxymethyl-2,4-dinitrobenzene sulfonic acid (HMDNBS) and its glycosylated product HMDNBS O-glucoside as the degradation products of 2,4-DNT-3-SO3Na, the major isoform of DNTS in TNT red water-contaminated soils, in switchgrass via LC-MS/MS- and NMR-based metabolite analyses. Transcriptomic analysis revealed that 15 UDP-glycosyltransferase genes were dramatically upregulated in switchgrass plants following 2,4-DNT-3-SO3Na treatment. We expressed, purified and assayed the activity of recombinant UGT proteins in vitro and identified PvUGT96C10 as the enzyme responsible for the glycosylation of HMDNBS in switchgrass. Overexpression of PvUGT96C10 in switchgrass significantly alleviated 2,4-DNT-3-SO3Na-induced plant growth inhibition. Notably, PvUGT96C10-overexpressing transgenic switchgrass plants removed 83.1% of 2,4-DNT-3-SO3Na in liquid medium after 28 days, representing a 3.2-fold higher removal rate than that of control plants. This work clarifies the DNTS detoxification mechanism in plants for the first time, suggesting that PvUGT96C10 is crucial for DNTS degradation. Our results indicate that PvUGT96C10-overexpressing plants may hold great potential for the phytoremediation of TNT red water-contaminated soils.

Carbazochrome sodium sulfonate and tranexamic acid combination therapy to reduce blood transfusions after 24 h of injury: A retrospective study.

Aim: Reducing the blood transfusion volume is important in severe trauma. We hypothesized that carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) would reduce blood transfusions in severe trauma. Methods: From April 2017 to March 2023, data were collected from patients (aged ≥16 years) admitted to our hospital for trauma and administered packed red blood cells (pRBC) and plasma transfusions within 12 h postinjury. Patients infused with CSS and TXA (CSS + TXA group) were compared with those infused with TXA alone (TXA group). The outcomes were blood product transfusion volumes within and after 24 h, the number of patients receiving >6 units of pRBC transfusion after 24 h, duration of intensive care unit and in-hospital stays, and 28-day in-hospital mortality. Results: In total, 138 patients were included in the study. In the univariate analyses, the CSS + TXA group (n = 62) showed a significant reduction in the total pRBC transfusion volume, in-hospital days, and number of patients receiving >6 units of pRBCs in the delayed phase. Based on the multivariate logistics regression analysis, only the CSS + TXA group had a significantly lower adjusted odds ratio for receiving >6 units of pRBC transfusion after 24 h. During the in-hospital days, the CSS + TXA group did not experience an increased incidence of major complications when compared with the TXA group. Conclusion: In patients with trauma, treatment with CSS with TXA may reduce the requirement for blood transfusion after 24 h. Moreover, this treatment can improve admission outcomes without increasing complications.