Accumulation Of Sulfate Research Articles

Reduction of lysosome abundance and GAG accumulation after odiparcil treatment in MPS I and MPS VI models

Deficiencies of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAG) cause pathologies commonly known as the mucopolysaccharidoses (MPS). Each type of MPS is caused by a deficiency in a specific GAG-degrading enzyme and is characterized by an accumulation of disease-specific GAG species. Previously, we have shown the potential of the beta-D-xyloside, odiparcil, as an oral GAG clearance therapy for Maroteaux-Lamy syndrome (MPS VI), an MPS characterized by an accumulation of chondroitin sulphate (CS) and dermatan sulphate (DS). This work suggested that odiparcil acts via diverting the synthesis of CS and DS into odiparcil-bound excretable GAG. Here, we investigated the effect of odiparcil on lysosomal abundance in fibroblasts from patients with MPS I and MPS VI. In MPS VI fibroblasts, odiparcil reduced the accumulation of a lysosomal-specific lysotracker dye. Interestingly, a reduction of the lysotracker dye was also observed in odiparcil-treated fibroblasts from patients with MPS I, a disorder characterized by an accumulation of DS and heparan sulphate (HS). Furthermore, odiparcil was shown to be effective in reducing CS, DS, and HS concentrations in liver and eye, as representative organs, in MPS VI and MPS I mice treated with 3 doses of odiparcil over 3 and 9 months, respectively. In conclusion, our data demonstrates odiparcil efficiently reduced lysosome abundance and tissue GAG concentrations in in vitro and in vivo models of MPS VI and MPS I and has potential as a treatment for these disorders.

Disease pathology signatures in a mouse model of Mucopolysaccharidosis type IIIB

Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare and devastating childhood-onset lysosomal storage disease caused by complete loss of function of the lysosomal hydrolase α-N-acetylglucosaminidase. The lack of functional enzyme in MPS IIIB patients leads to the progressive accumulation of heparan sulfate throughout the body and triggers a cascade of neuroinflammatory and other biochemical processes ultimately resulting in severe mental impairment and early death in adolescence or young adulthood. The low prevalence and severity of the disease has necessitated the use of animal models to improve our knowledge of the pathophysiology and for the development of therapeutic treatments. In this study, we took a systematic approach to characterizing a classical mouse model of MPS IIIB. Using a series of histological, biochemical, proteomic and behavioral assays, we tested MPS IIIB mice at two stages: during the pre-symptomatic and early symptomatic phases of disease development, in order to validate previously described phenotypes, explore new mechanisms of disease pathology and uncover biomarkers for MPS IIIB. Along with previous findings, this study helps provide a deeper understanding of the pathology landscape of this rare disease with high unmet medical need and serves as an important resource to the scientific community.

Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1

Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI. The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury. Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1α (HNF-1α) and pregnane X receptor (PXR). These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.

Establishment of the Effectiveness of Early Versus Late Stem Cell Gene Therapy in Mucopolysaccharidosis II for Treating Central Versus Peripheral Disease.

Mucopolysaccharidosis type II (MPSII) is a rare pediatric X-linked lysosomal storage disease, caused by heterogeneous mutations in the iduronate-2-sulfatase (IDS) gene, which result in accumulation of heparan sulfate (HS) and dermatan sulfate within cells. This leads to severe skeletal abnormalities, hepatosplenomegaly, and cognitive deterioration. The progressive nature of the disease is a huge obstacle to achieve full neurological correction. Although current therapies can only treat somatic symptoms, a lentivirus-based hematopoietic stem cell gene therapy (HSCGT) approach has recently achieved improved central nervous system (CNS) neuropathology in the MPSII mouse model following transplant at 2 months of age. In this study, we evaluate neuropathology progression in 2-, 4- and 9-month-old MPSII mice, and using the same HSCGT strategy, we investigated somatic and neurological disease attenuation following treatment at 4 months of age. Our results showed gradual accumulation of HS between 2 and 4 months of age, but full manifestation of microgliosis/astrogliosis as early as 2 months. Late HSCGT fully reversed the somatic symptoms, thus achieving the same degree of peripheral correction as early therapy. However, late treatment resulted in slightly decreased efficacy in the CNS, with poorer brain enzymatic activity, together with reduced normalization of HS oversulfation. Overall, our findings confirm significant lysosomal burden and neuropathology in 2-month-old MPSII mice. Peripheral disease is readily reversible by LV.IDS-HSCGT regardless of age of transplant, suggesting a viable treatment for somatic disease. However, in the brain, higher IDS enzyme levels are achievable with early HSCGT treatment, and later transplant seems to be less effective, supporting the view that the earlier patients are diagnosed and treated, the better the therapy outcome.

Oxalate-Promoted SO2 Uptake and Oxidation on Iron Minerals: Implications for Secondary Sulfate Aerosol Formation.

Mineral dust serves as a significant source of sulfate aerosols by mediating heterogeneous sulfur dioxide (SO2) oxidation in the atmosphere. Given that a considerable proportion of small organic acids are deposited onto mineral dust via long-range transportation, understanding their impact on atmospheric SO2 transformation and sulfate formation is of great importance. This study investigates the effect of oxalate on heterogeneous SO2 uptake and oxidation phenomenon by in situ FTIR, theoretical calculation, and continuous stream experiments, exploiting hematite (Fe2O3) as an environmental indicator. The results highlight the critical role of naturally deposited oxalate in mononuclear monodentate coordinating surface Fe atoms of Fe2O3 that enhances the activation of O2 for oxidizing SO2 into sulfate. Meanwhile, oxalate increases the hygroscopicity of Fe2O3, facilitating H2O dissociation into reactive hydroxyl groups and further augmenting the SO2 uptake capacity of Fe2O3. More importantly, other conventional iron minerals, such as goethite and magnetite, as well as authentic iron-containing mineral dust, exhibit similar oxalate-promoted sulfate accumulation behaviors. Our findings suggest that oxalate-assisted SO2 oxidation on iron minerals is one of the important contributors to secondary sulfate aerosols, especially during the nighttime with high relative humidity.

Ni/Al2O3 waste catalyst loaded with pomegranate peel extract and Ce3+ ions as a sustainable active/barrier pigment for epoxy anti-corrosion coating

Nickel-containing alumina (Ni/Al2O3) is a commercially available catalyst that is widely used for desulfurizing crude oil components. However, the accumulation of carbon and sulfur on the catalyst surface can lead to its deactivation, making its disposal environmentally hazardous. Additionally, extracting nickel from waste catalysts is not economically feasible. The high specific surface area of Ni/Al2O3 waste catalyst (Cat), which can exceed 100 m2/g, makes it a promising material for repurposing as nanocontainers for anti-corrosive coatings. In this study, an intelligent epoxy (EP) anti-corrosion coating incorporating Cat for encapsulating a green hybrid corrosion inhibitor based on pomegranate peel extract (PPE) and Ce3+ ions was developed. Brunauer-Emmett-Teller (BET) analysis revealed that Cat nanopigment possessed a mesoporous structure and a surface area of 127 m2/g, rendering it a suitable candidate for encapsulating corrosion inhibitors. Fourier-transform infrared spectroscopy (FTIR), BET, and thermogravimetric analysis (TGA) were employed to confirm inhibitor loading in the Cat nanopigment. The self-healing and protective properties of the prepared EP-based composite coatings were evaluated using salt spray and electrochemical impedance spectroscopy (EIS) tests. The findings demonstrated a 440% improvement in the overall corrosion resistance (RT) of Ce-PPE@Cat/EP coating compared to blank/EP coatings.

Promoting effect of Si on MnOx catalysts for low-temperature NH3-SCR of NO: Enhanced N2 selectivity and SO2 resistance

Manganese-based catalysts have excellent catalytic performance for the effective removal of NOx in low-temperature flue gas through selective catalytic reduction with NH3 (NH3-SCR). However, the catalysts suffer from poor SO2 resistance and N2 selectivity in the actual process, which still need to be solved. In this study, MnOx-SiO2 mixed oxide catalysts were designed and prepared by coprecipitation method to improve the SO2 resistance and N2 selectivity in NH3-SCR process. In the presence of 100 ppm SO2, MnOx-SiO2(0.72) catalyst showed excellent sulfur resistance with the conversion of NOx reached 95 % even after introducing SO2 for 8 h. The doping of SiO2 greatly improved the specific surface area and surface acidity of the catalyst, which was conducive to the adsorption of NH3. Meanwhile, the redox performance of the catalyst was decreased, improving the N2 selectivity. The study on the sulfur resistance mechanism revealed that the doping of SiO2 reduced the adsorption of SO2 on the surface of catalyst, protecting the active components and avoiding the accumulation of sulfates, thus achieving good sulfur resistance performance. This work provided an environmentally friendly NH3-SCR catalyst by inhibiting SO2 adsorption to have good catalytic performance and SO2 resistance.

Bioleaching of Zinc from Blast Furnace Cast House Dust

Metallurgical dusts are by-products from steel manufacturing. The high iron content of cast house dust (~64%) makes this by-product an interesting iron feedstock alternative. Therefore, its return into the internal steelmaking circuit, specifically in the sinter plant, is a common practice in the steel industry. However, this dust fraction also contains heavy metals, as zinc. As a result of the re-entry of zinc into the process, the zinc concentration in the blast furnace flue gas dust also increases. This prevents the full recirculation of the blast furnace flue gas dust in the steelmaking process despite its relatively high iron content (~35%), thus causing part of the blast furnace flue gas dust to end in the landfill. The goal of this study was to investigate the usage of bacteria, such as the sulfur oxidizing Acidithiobacillus thiooxidans or the iron and sulfur oxidizing Acidithiobacillus ferrooxidans, to leach the undesirable element zinc from the cast house dust while preventing the leaching of iron, by adjusting the sulfur addition and avoiding, at the same time, the accumulation of sulfur in the solid fraction. Experiments proved that a co-culture of A. thiooxidans and A. ferrooxidans can effectively leach zinc from metallurgical dusts, maintaining high iron concentrations in the material. The influence of elemental sulfur on the efficiencies reached was shown, since higher removal efficiencies were achieved with increasing sulfur concentrations. Maximum zinc leaching efficiencies of ~63% (w/w) and an iron enrichment of ~7% (w/w) in the remaining residue were achieved with sulfur concentrations of 15 g/L for cast house gas concentrations of 125 g/L.

From Sphagnum to shrub: Increased acidity reduces peat bacterial diversity and keystone microbial taxa imply peatland degradation

AbstractPeatlands store one‐third of the Earth's carbon. Human activities and climate change‐induced peatland vegetation shift from Sphagnum to shrub may lead to peatland degradation. To understand the ecology and functions of these peatlands, we collected samples from 10 peatland mosaics dominated by Sphagnums, mixed plant communities of Sphagnums, and shrubs across south China. Through sequencing the plant rhizosphere microbiome and measuring peat properties, we explored the plant–soil interactions and identified the keystone microbial taxa in peatlands of three vegetation types. Results showed that peat pH decreased along with the plant community shift from Sphagnum to shrub, which may be due to the accumulation of sulfur and phenolics. Lower pH further reduced bacterial diversity in shrub peatlands as Acidobacteriota became predominant in the keystone taxa. Overall, microbiomes in shrub peatlands showed degraded properties, such as a less stable microbial community dominated by few keystone taxa and the loss of methane‐mitigating microbes. The keystone microbial taxa in Sphagnum peatlands included microbes that utilize insoluble organic substances, mono‐ and oligo‐saccharides. Most importantly, the methanotrophic microbes that oxidize methane only appeared in the keystone taxa of Sphagnum peatlands. Mixed plant community peatlands contained the highest concentrations of iron. Slow‐growing fungi and bacteria were in the keystone microbial taxa, indicating slow decomposition rates in these peatlands. Our study suggests that human activity and climate change‐induced peatland vegetation shift from Sphagnum to shrub leads to an unstable belowground community, indicating the degraded peatland, which may exacerbate in the future.

Gut Microbiome and Microbiome-Derived Metabolites in Patients with End-Stage Kidney Disease.

The composition of the gut microbiome is altered in patients with chronic kidney disease (CKD). Dysbiosis leads to decreased levels of stool organic acids (OAs) and systemic inflammation, followed by accumulation of uremic toxins (UTs) and the development of end-stage kidney disease (ESKD). We assessed the relationship between the microbiome and UT levels or the development of ESKD by comparing patients undergoing hemodialysis (HD) and those with normal renal function (NRF). This cross-sectional study recruited 41 patients undergoing HD and 38 sex- and age-matched patients with NRF, and gut microbiome, levels of plasma UTs, inflammatory markers, and stool OAs were compared. The indices of beta-diversity differed significantly between patients with NRF and those undergoing HD, and between patients undergoing HD with and without type 2 diabetes. The levels of stool total OA, inflammatory markers, and UTs differed significantly between the patients with NRF and those undergoing HD. The combined main effects of type 2 diabetes and kidney function status were accumulation of indoxyl sulfate and p-cresyl sulfate. The relative abundances of Negativicutes and Megamonas were associated with development of ESKD and with the levels of UTs, even after adjustment for factors associated with the progression of ESKD. The present study indicates that the gut environment differs between patients with NRF and those undergoing HD and between patients undergoing HD with and without type 2 diabetes. Moreover, ESKD patients with diabetes accumulate more UTs derived from the gut microbiome, which might be associated with cardio-renal diseases and poor prognosis.

Fusion of Rabies Virus Glycoprotein or gh625 to Iduronate-2-Sulfatase for the Treatment of Mucopolysaccharidosis Type II.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a mutation in the IDS gene, resulting in deficiency of the enzyme iduronate-2-sulfatase (IDS) causing heparan sulfate (HS) and dermatan sulfate (DS) accumulation in all cells. This leads to skeletal and cardiorespiratory disease with severe neurodegeneration in two thirds of sufferers. Enzyme replacement therapy is ineffective at treating neurological disease, as intravenously delivered IDS is unable to cross the blood-brain barrier (BBB). Hematopoietic stem cell transplant is also unsuccessful, presumably due to insufficient IDS enzyme production from transplanted cells engrafting in the brain. We used two different peptide sequences (rabies virus glycoprotein [RVG] and gh625), both previously published as BBB-crossing peptides, fused to IDS and delivered via hematopoietic stem cell gene therapy (HSCGT). HSCGT with LV.IDS.RVG and LV.IDS.gh625 was compared with LV.IDS.ApoEII and LV.IDS in MPS II mice at 6 months post-transplant. Levels of IDS enzyme activity in the brain and peripheral tissues were lower in LV.IDS.RVG- and LV.IDS.gh625-treated mice than in LV.IDS.ApoEII- and LV.IDS-treated mice, despite comparable vector copy numbers. Microgliosis, astrocytosis, and lysosomal swelling were partially normalized in MPS II mice treated with LV.IDS.RVG and LV.IDS.gh625. Skeletal thickening was normalized by both treatments to wild-type levels. Although reductions in skeletal abnormalities and neuropathology are encouraging, given the low levels of enzyme activity compared with control tissue from LV.IDS- and LV.IDS.ApoEII-transplanted mice, the RVG and gh625 peptides are unlikely to be ideal candidates for HSCGT in MPS II and are inferior to the ApoEII peptide that we have previously demonstrated to be more effective at correcting MPS II disease than IDS alone.

Generation, activation, and recycling of ammonium persulfate for the remediation of organic-contaminated soil: System construction, process, and mechanisms

Persulfate advanced oxidation processes (PS-AOPs) are among the most promising methods of remediating organic-contaminated soil. However, the application of this technology is restricted by high costs associated with the single use of large amounts of PS and great environmental risks associated with the accumulation of sulphate in the soil after remediation. Therefore, in this study, we proposed and tested a circulation system for soil remediation that more efficiently activates and regenerates PS. By using porous carbon felts as ‘flow-though’ electrodes, a high concentration of PS was generated in the carbon anode and then co-activated by electrons and carbon in the carbon cathode. In this process, electron transfer, rather than mass transport, was revealed as the rate-controlling step. Soil remediation experiments indicated that non-radical oxidation with carbon-activated, transition-state PS* and radical oxidation with SO4−∙ and ∙OH collectively contribute to the degradation of naphthalene in organic-contaminated soil. By analysing the mechanism of competition between PS regeneration and reactions involving soil impurities in the carbon anode, it was found that leached organic pollutants were degraded in a timely manner when passing through the carbon anode, with negligible impact on PS regeneration. Finally, this system demonstrated high stability and wide applicability, based on the characterisation of electrodes and evaluation of environmental impact parameters. These findings provide a theoretical and practical basis for reducing the application cost and ecological risk of PS-AOPs in the remediation of organic-contaminated soil.

Heat Soaking for Improving Rollover From S at the Back of CIGSSe Solar Cells

A simple method of low-temperature heat-soaking (HS) treatment on copper indium gallium sulfur selenide (CIGSSe) solar cells is investigated for mitigating the rollover effect. Excessive sulfur accumulation on the backside of the CIGSSe absorber leads to downward valence band bending and forms a Schottky barrier, resulting in the rollover current–voltage characteristic at room temperature. HS treatment effectively reduces current saturation in the first quadrant of the current–voltage curves and improves cell efficiency on average by more than 6%. The depth profile on exfoliated CIGSSe absorbers from the Auger electron spectroscopy analysis demonstrates the elemental redistribution, indicating that HS treatment can change the profile gradient of sulfur. The width of sulfur accumulation is significantly reduced after HS, which enables Fowler–Nordheim tunneling by Schottky barrier width shortening. This study showcases a straightforward process and easy-to-implement strategy to reduce the second reverse diode effect caused from the sulfurization process.

Geochemistry of Salt Lakes of East Kazakhstan

The main purpose of this study is to determine the chemical composition of salt lakes in the borovoye, Delbegetei and Chagan-Shar sites (East Kazakhstan). For the study, samples were selected for analytical studies, as well as field surveys were conducted on the geometrization and linking of lakes within the borovoye, Delbegetey and Chagan-Shar sites and sampling of Water, bottom sediments, rapes. 44 water samples, 66 rapes and bottom sediments were taken. The main cation is sodium, which contains from 50.28 to 2539.04 mg/l, with an average value of 798.9 mg/L (60 mg-EQ %). The relative composition of the second is 25 mg-EQ % of calcium, and magnesium is 15 mg-eq % [1]. Only the sulphate type of lakes differs in the ash-Shar section. According to the chemical composition of lakes of the sulphate type, all 11 lakes are characterized by relatively low mineralization, with an average pH range of 7.4 to 8.8 and belong to freshwater. High values of hydrocarbonates are observed in Lake 7SH at 2976 mg/L, on average, the proportion of sulfate ions is 46 mg-EQ%. It was found that the increase in salinity in the waters of the studied lakes of East Kazakhstan is not due to the accumulation of sulfates and chlorides in the water, and the composition increases in proportion to the salinity.

Analysis of Regulatory Mechanism of AcrB and CpxR on Colistin Susceptibility Based on Transcriptome and Metabolome of Salmonella Typhimurium.

With the increasing and inappropriate use of colistin, the emerging colistin-resistant isolates have been frequently reported during the last few decades. Therefore, new potential targets and adjuvants to reverse colistin resistance are urgently needed. Our previous study has confirmed a marked increase of colistin susceptibility (16-fold compared to the wild-type Salmonella strain) of cpxR overexpression strain JSΔacrBΔcpxR::kan/pcpxR (simplified as JSΔΔ/pR). To searching for potential new drug targets, the transcriptome and metabolome analysis were carried out in this study. We found that the more susceptible strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels. The virulence-related genes and colistin resistance-related genes (CRRGs) were significantly downregulated in JSΔΔ/pR. There were significant accumulation of citrate, α-ketoglutaric acid, and agmatine sulfate in JSΔΔ/pR, and exogenous supplement of them could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. Additionally, we also demonstrated that AcrB and CpxR could target the ATP and reactive oxygen species (ROS) generation, but not proton motive force (PMF) production pathway to potentiate antibacterial activity of colistin. Collectively, these findings have revealed several previously unknown mechanisms contributing to increased colistin susceptibility and identified potential targets and adjuvants for potentiating colistin treatment of Salmonella infections. IMPORTANCE Emergence of multidrug-resistant (MDR) Gram-negative (G-) bacteria have led to the reconsideration of colistin as the last-resort therapeutic option for health care-associated infections. Finding new drug targets and strategies against the spread of MDR G- bacteria are global challenges for the life sciences community and public health. In this paper, we demonstrated the more susceptibility strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels and revealed several previously unknown regulatory mechanisms of AcrB and CpxR on the colistin susceptibility. Importantly, we found that exogenous supplement of citrate, α-ketoglutaric acid, and agmatine sulfate could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. These results provide a theoretical basis for finding potential new drug targets and adjuvants.

Анализ накопления подвижной серы в почве города Атырау

The article analyzes the accumulation of mobile sulfur in the soil of the city of Atyrau. Atyrau city is located in the western part of the Republic of Kazakhstan. The main source of pollution of the city of Atyrau is the Atyrau Oil Refinery. The increased content of hydrogen sulfide in the air involves an analysis of the accumulation of sulfur in the soil, as well as establishing a relationship with the incoming hydrogen sulfide from the air. The content of mobile sulfur in the soil was determined by photometric method in the Testing Laboratory of Analytical Laboratory for Environmental Protection LLP. Accumulations of sulfur in the soil were recorded at observation points located near the Atyrau oil refinery, for example, at the observation point of Khimposelok, Mirny, Proparka. There is no such pattern in observation points located in populated areas. At the point of PNZ 1, an increased sulfur content is observed in the soil due to its close location to the Kvadrat evaporator pond.

#6315 CHARACTERIZATION OF BRAIN DAMAGE AFTER ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) is a very common condition in inpatients. Severe AKI is frequently associated with by neurological disorders such as confusion, the mechanisms of which are poorly understood. We have shown in several animal models that chronic kidney disease is associated with impaired cognitive performance such as memory and increased permeability of the blood-brain barrier (BBB), related to the accumulation of uremic toxin indoxyl sulfate. The goal of these experiments was to highlight the influence of AKI on cerebral impairment in mice, particularly the BBB permeability, and to describe the mechanisms involved. Method We performed an AKI in C57/Bl6 WT mice, by unilateral nephrectomy and transient ischemia-reperfusion of the remaining kidney for 20 minutes (RIRI20 group) and compared them to two other groups: control mice and mice with unilateral ischemia-reperfusion without nephrectomy (IR20). Modified neurological severity score (mNSS) was performed daily. BBB permeability was assessed by quantification of the Evans Blue leakage in the brain and by cerebral 68Ga-DTPA TEP/CT imaging. Cerebral immuno-histochemistry was performed to evaluate the neuro-inflammatory processes. Results Glomerular filtration rate at Day 1 was lower in AKI group compared to the control group 0.21 ± 0.26 vs. 0.94 ± 0.13 mL/min/100g b.w (p<0.0001) and IR group: 0.75 ± 0.17 mL/min/100g b.w (p = 0.0007). Mice with AKI displayed a neurological impairment at day 1 and day 2 post-AKI, compared to control mice and IR20 mice, with mainly an impairment of the balance. Mean mNSS score at Day 1 was 2.6 ± 4.5 in AKI group, and 0.0 ±-0.0 in both the control and IR groups (p = 0.002). BBB permeability at Day 2 was higher in the AKI group than in the control group (p = 0.10) and the IR group (p = 0.0006) by Evans blue staining. Cerebral TEP imaging found similar results with increased BBB permeability in AKI mice to compared to control mice at D1 and D2 (p = 0.004 and p = 0.009, respectively). On immunohistochemistry, brains of mice after AKI displayed more astrocytosis and microglial activation compared to brains of control mice. Conclusion AKI in mice is specifically associated with early neurological damage, unlike renal ischemia-reperfusion alone, related to a BBB disruption in the first two days after AKI. AKI appears to induce astrocytosis and altered microglial phenotype, potentially due to increased neuroinflammatory processes following BBB disruption.

Neurocognitive testing in a murine model of mucopolysaccharidosis type IIIA

Mucopolysaccharidosis type IIIA (MPS IIIA) is an inherited metabolic disorder caused by a lysosomal enzyme deficiency resulting in heparan sulphate (HS) accumulation and manifests with a progressive neurodegenerative phenotype. A naturally occurring MPS IIIA mouse model is invaluable for preclinical evaluation of potential treatments but the ability to effectively assess neurological function has proved challenging. Here, the aim was to evaluate a set of behaviour tests for their reliability in assessing disease progression in the MPS IIIA mouse model. Compared to wild-type (WT) mice, MPS IIIA mice displayed memory and learning deficits in the water crossmaze from mid-stage disease and locomotor impairment in the hind-limb gait assessment at late-stage disease, supporting previous findings. Declined wellbeing was also observed in the MPS IIIA mice via burrowing and nest building evaluation at late-stage disease compared to WT mice, mirroring the progressive nature of neurological disease. Excessive HS accumulation observed in the MPS IIIA mouse brain from 1 month of age did not appear to manifest as abnormal behaviours until at least 6 months of age suggesting there may be a threshold of HS accumulation before measurable neurocognitive decline. Results obtained from the open field and three-chamber sociability test are inconsistent with previous studies and do not reflect MPS IIIA patient disease progression, suggesting these assessments are not reliable. In conclusion, water cross-maze, hind-limb gait, nest building and burrowing, are promising assessments in the MPS IIIA mouse model, which produce consistent results that mimic the human disease.

Effects of SO2 on NH4NO3 Photolysis: The Role of Reducibility and Acidic Products.

Nitrate photolysis is a vital process in secondary NOx release into the atmosphere. The heterogeneous oxidation of SO2 due to nitrate photolysis has been widely reported, while the influence of SO2 on nitrate photolysis has rarely been investigated. In this study, the photolysis of nitrate on different substrates was investigated in the absence and presence of SO2. In the photolysis of NH4NO3 on the membrane without mineral oxides, NO, NO2, HONO, and NH3 decreased by 17.1, 6.0, 12.6, and 57.1% due to the presence of SO2, respectively. In the photolysis of NH4NO3 on the surface of mineral oxides, SO2 also exhibited an inhibitory effect on the production of NOx, HONO, and NH3 due to its reducibility and acidic products, while the increase in surface acidity due to the accumulation of abundant sulfate on TiO2 and MgO promoted the release of HONO. On the photoactive oxide TiO2, HSO3-, generated by the uptake of SO2, could compete for holes with nitrate to block nitrate photolysis. This study highlights the interaction between the heterogeneous oxidation of SO2 and nitrate photolysis and provides a new perspective on how SO2 affects the photolysis of nitrate absorbed on the photoactive oxides.

Suppressing Effects of Docosahexaenoic Acid-Containing Diets on Oxidative Stress and Fibrosis in 5/6 Nephrectomized Rats.

Urinary albumin excretion gradually increases after nephrectomy, which eventually progresses toward renal failure. Our previous study had reported that arachidonic acid (ARA)- or/and docosahexaenoic acid (DHA)-containing diet attenuates the increasing urinary albumin excretion. The current study aimed to investigate the effects of ARA- or/and DHA-containing diets on oxidative stress and fibrosis that cause kidney injury in 5/6 nephrectomy rats. Sprague Dawley rats were randomly divided into control group, ARA group, DHA group, and ARA + DHA group. Rats underwent 5/6 kidney removal and were fed ARA or/and DHA containing diet each five groups continuously for 4 weeks. We collected urine, plasma, and kidney samples 4 weeks after surgery, and investigated the effects of ARA- and DHA-containing diets on oxidative stress, inflammation, and fibrosis in kidney. Urinary albumin excretion, indoxyl sulfate, reactive oxygen species, and tumor necrosis factor-α levels, and fibrosis in kidney were all increased upon nephrectomy; they were, however, attenuated after feeding the rats with DHA-containing diet. One possible mechanism of preventing chronic renal failure would be the suppression of indoxyl sulfate accumulation, oxidative stress, and kidney fibrosis arising due to nephrectomy. The results collectively suggested that DHA-containing diets can suppress the progression of renal failure.