Sulfate Levels Research Articles

Retention of indoxyl sulfate in different genotypes of ABCC2 may explain variation in tacrolimus pharmacokinetics

Background Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the in vivo role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics. Methods Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status. Results Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the ABCC2 normal function (β = −0.740, p = 0.020) and reduced function groups (β = −0.526, p = 0.005), respectively, showing a strong correlation with tacrolimus. Conclusion ABCC2 may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.

Effect of a Web-Based Heartfulness Program on the Mental Well-Being, Biomarkers, and Gene Expression Profile of Health Care Students: Randomized Controlled Trial.

Health care students often experience high levels of stress, anxiety, and mental health issues, making it crucial to address these challenges. Variations in stress levels may be associated with changes in dehydroepiandrosterone sulfate (DHEA-S) and interleukin-6 (IL-6) levels and gene expression. Meditative practices have demonstrated effectiveness in reducing stress and improving mental well-being. This study aims to assess the effects of Heartfulness meditation on mental well-being, DHEA-S, IL-6, and gene expression profile. The 78 enrolled participants were randomly assigned to the Heartfulness meditation (n=42, 54%) and control (n=36, 46%) groups. The participants completed the Perceived Stress Scale (PSS) and Depression Anxiety Stress Scale (DASS-21) at baseline and after week 12. Gene expression with messenger RNA sequencing and DHEA-S and IL-6 levels were also measured at baseline and the completion of the 12 weeks. Statistical analysis included descriptive statistics, paired t test, and 1-way ANOVA with Bonferroni correction. The Heartfulness group exhibited a significant 17.35% reduction in PSS score (from mean 19.71, SD 5.09 to mean 16.29, SD 4.83; P<.001) compared to a nonsignificant 6% reduction in the control group (P=.31). DASS-21 scores decreased significantly by 27.14% in the Heartfulness group (from mean 21.15, SD 9.56 to mean 15.41, SD 7.87; P<.001) while it increased nonsignificantly by 17% in the control group (P=.04). For the DASS-21 subcomponents-the Heartfulness group showed a statistically significant 28.53% reduction in anxiety (P=.006) and 27.38% reduction in stress (P=.002) versus an insignificant 22% increase in anxiety (P=.02) and 6% increase in stress (P=.47) in the control group. Further, DHEA-S levels showed a significant 20.27% increase in the Heartfulness group (from mean 251.71, SD 80.98 to mean 302.74, SD 123.56; P=.002) compared to an insignificant 9% increase in the control group (from mean 285.33, SD 112.14 to mean 309.90, SD 136.90; P=.10). IL-6 levels showed a statistically significant difference in both the groups (from mean 4.93, SD 1.35 to mean 3.67, SD 1.0; 28.6%; P<.001 [Heartfulness group] and from mean 4.52, SD 1.40 to mean 2.72, SD 1.74; 40%; P<.001 [control group]). Notably, group comparison at 12 weeks revealed a significant difference in perceived stress, DASS-21 and its subcomponents, and IL-6 (all P<.05/4). The gene expression profile with messenger RNA sequencing identified 875 upregulated genes and 1539 downregulated genes in the Heartfulness group compared to baseline, and there were 292 upregulated genes and 1180 downregulated genes in the Heartfulness group compared to the control group after the intervention. Heartfulness practice was associated with decreased depression, anxiety, and stress scores and improved health measures in DHEA-S and IL-6 levels. The gene expression data point toward possible mechanisms of alleviation of symptoms of stress, anxiety and depression. ISRCTN Registry ISRCTN82860715; https://doi.org/10.1186/ISRCTN82860715.

Impact of Laboratory-Measured Euthyroid Hashimoto's Thyroiditis on Reproductive Hormone Profile in Women with Obesity.

Introduction: Hashimoto's thyroiditis is a common endocrinological disorder that often coexists with obesity. Thyroid hormones interact with the regulation of sex steroids, and thyroid autoimmunity has a negative impact on female fertility. There are studies showing when euthyroid state is achieved with hormone replacement therapy (HRT), the reproductive hormone profile is improved but they usually compare the reproductive hormones before and after HRT in the same individuals. Studies comparing patients with Hashimoto's thyroiditis in an euthyroid state receiving HRT with individuals having normal thyroid function are limited. Here, it was aimed to search the impact of euthyroid Hashimoto's thyroiditis on reproductive hormone profile in women living with obesity. Materials and Methods: Sixty-one randomly selected female patients with Hashimoto's thyroiditis were included as the case group and 60 patients without Hashimoto's thyroiditis were included as the control group, from our obesity center. The case group included patients who had menstrual cycles and were euthyroid under l-thyroxine treatment for at least 6 months. Data on weight, height, body mass index (BMI), waist circumference (WC), free thyroxine (fT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), cortisol, insulin, prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (prog), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) levels, l-thyroxine treatment dosage (for case group), and accompanying diseases were recorded. The results were evaluated using SPSS. Results: A total of 121 patients were included in the study. Mean age was 41.8 ± 8.5 years in case and 38.6 ± 8.9 years in control group. There was no significant difference in weight, height, BMI, WC, or accompanying diseases between Hashimoto's thyroiditis and control group. fT4, anti-TPO, cortisol levels were higher in Hashimoto's thyroiditis group when compared with control group, but there was no significant difference for TSH, insulin, FSH, LH, E2, prog, T, DHEAS, or PRL. Conclusion: In women living with obesity, it is important to screen for Hashimoto's thyroiditis and achieve euthyroidism through effective LT4 treatment to promote a healthy reproductive system and improve fertility rates.

Indoxyl Sulfate and Autism Spectrum Disorder: A Literature Review.

Indoxyl sulfate-a bacterially derived metabolite-has been identified as a toxin that is elevated in children with autism spectrum disorder (ASD). As a neurotoxin, uremic toxin, nephrotoxin, cardiotoxin, osteotoxin, and myotoxin, indoxyl sulfate has been associated with several other conditions, including chronic kidney disease, acute kidney injury, Parkinson's disease, cognitive disorders, and mood disorders such as anxiety and depression. Indoxyl sulfate is derived from bacterial modification of host tryptophan, and elevated levels of indoxyl sulfate are associated with decreased levels of important neurotransmitters including serotonin, dopamine, and norepinephrine. This article will review what is currently known about indoxyl sulfate in relation to ASD and its comorbidities. A systematic review identified six studies of levels of indoxyl sulfate in children with ASD. All six studies found that indoxyl sulfate was significantly elevated in the urine of children with ASD compared to typically developing children. Through this review, indoxyl sulfate was identified as a toxic microbially derived metabolite that is significantly increased in a subset of children with ASD and may contribute to both core and co-morbid ASD symptoms.

Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis.

Epidemiological evidence indicates that trace elements are significantly associated with cardiovascular health. However, its causality and underlying mechanisms remain unclear. Therefore, this study aimed to investigate the causal relationship between trace elements and cardiovascular disease, as well as their potential mechanism of action. Two-sample Mendelian randomization (MR) analyses along with mediated and multivariate MR analyses were employed. These analyses utilized 13 trace elements as exposure variables and 20 cardiovascular diseases as outcome variables, with 4907 circulating plasma proteins, 1400 serum metabolites, 731 immune cell phenotypes, and 473 intestinal flora as potential mediators. The Bayesian weighted MR method was used to validate the MR results, and linkage disequilibrium score regression (LDSC) was applied to explore the genetic correlation between trace elements and cardiovascular disease. Our findings indicated a positive or negative causal relationship between genetically predicted trace elements and cardiovascular disease. An analysis using the Bayesian weighted MR method demonstrated that our causal inference results were reliable. The results of the mediated MR analyses indicate that potassium may reduce the risk of ischemic heart disease by influencing the expression of the plasma proteins BDH2 and C1R. Vitamin B12 may increase the risk of coronary atherosclerosis and cardiovascular death by reducing the levels of VPS29 and PSME1 proteins, while vitamin C may mitigate the risk of cardiac arrest by inhibiting the expression of the TPST2 protein. In addition, potassium can reduce the risk of ischemic heart disease by lowering 4-methoxyphenyl sulfate levels. None of the instrumental variables exhibited pleiotropy in the MR analysis. A sensitivity analysis using the leave-one-out method further confirmed the robustness of our findings. LDSC results indicated a genetic correlation between multiple trace elements and various cardiovascular diseases. This study uncovered the true causal relationship between trace elements and cardiovascular disease risk using genetic methods, and revealed the significant mediating role of specific plasma proteins and metabolites in this relationship.

Wastewater Quality Assessment at Amarah Sewage Treatment Plant: Implications for Agricultural Use and Environmental Safety

This study examines the quality of treated wastewater from the Amarah Sewage Treatment Plant (ASTP) in Iraq for potential agricultural use and compares it to the water quality standards of Iraq, Egypt, and the USA. The effluent was analyzed over a five-month period for various parameters, including pH, Total Suspended Solids (TSS), Total Dissolved Solids (TDS), and concentrations of ions, such as chloride (Cl-), sulfate (SO4-2), phosphate (PO43-), nitrate (NO3-), and ammonia (NH3). The findings showed that the pH and TDS measurements of the treated wastewater fell within the acceptable range, according to the regulations set by all three countries. The concentrations of Cl-, SO4-2, PO43-, NO3-, and NH3 in the treated wastewater were also within the acceptable limits set by the Iraqi standards. However, chloride and sulfate levels occasionally exceed permissible thresholds. The treated wastewater from ASTP is generally suitable for the irrigation of certain crops, but it is important to implement a monitoring and control system to ensure consistent water quality. Finally, investments are needed to improve treatment processes and establish educational programs for farmers to enhance their understanding of proper wastewater usage. These measures are crucial for protecting public health and conserving water resources, particularly in regions facing water scarcity.

The effects of WWP1 overexpression on the golgi apparatus stress response and proteoglycan production in adipocytes

White adipocytes are a major component of white adipose tissue (WAT) and help to maintain systemic metabolic homeostasis by storing energy and secreting adipokines. In mice deficient in the protein WWP1 (WW domain-containing E3 ubiquitin protein ligase 1), oxidative stress in adipocytes increases but insulin resistance induced by obesity improves. However, the specific roles of WWP1 in adipocytes remain unclear. Here, we show that in 3T3L1 adipocytes, WWP1 localized in the Golgi apparatus via its C2 domain, where it protected the Golgi apparatus from monensin-induced disruption. By contrast, WWP1 knockdown by short hairpin RNA failed to protect the Golgi apparatus and enhanced Golgi apparatus disruption by monensin. The Golgi apparatus acts as a central organelle to establish accurate protein glycosylation of proteoglycans containing glycosaminoglycans, including chondroitin sulfate and heparan sulfate (HS). WWP1 overexpression increased chondroitin sulfate and HS levels, whereas WWP1 knockdown decreased them. Furthermore, obesity-related increases in HS were prevented by WWP1 knockout in adipose tissue. In summary, our results demonstrate a novel role for WWP1 in maintaining Golgi apparatus morphology and proteoglycan synthesis in adipocytes.

Understanding the Global Distribution of Groundwater Sulfate and Assessing Population at Risk.

Besides sulfate-induced diarrhea, recent studies have emphasized that groundwater sulfate drives the release of arsenic in groundwater and accelerates water pipeline corrosion. Despite its impact on public health and urban infrastructure, sulfate has been overlooked in water supply research. Here, we used a random forest model to develop a 1 km global map depicting the probability of sulfate exceeding 250 mg/L in groundwater based on the World Health Organization's guidelines. The map was further applied to estimate the exposed population and identify contributors of sulfate exceedance in global hotspot regions. The results revealed that sulfate exceedance in groundwater was widespread in 156 countries. Approximately 194 million people use water with sulfate levels exceeding 250 mg/L. Among them, around 17 million people face groundwater sulfate concentrations surpassing 500 mg/L, with 82% of these individuals residing in ten specific countries. Contributing factor analysis in these countries indicates that annual precipitation and sedimentary rocks are the primary factors contributing to sulfate concentration prediction, while other natural and anthropogenic predictors exhibit region-specific impact patterns. This study uncovered a significant prevalence of elevated sulfate levels in groundwater, highlighting the need to integrate sulfate into water safety management practices.

The Characteristics of Water-Soluble Inorganic Ions in PM1.0 and Their Impact on Visibility at a Typical Coastal Airport

Water-soluble inorganic ions (WSIIs) can increase the hygroscopicity of aerosols, which will transform aerosols into larger sizes and reduce visibility by enhancing light scattering. To explore the characteristics of WSII concentrations and their impacts on visibility in a coastal airport, in this study, PM1.0 samples at two monitoring sites (including airport site and background site) were collect in spring and summer, and 12 species of ions were detected. In general, secondary water-soluble inorganic ions (SNA, including SO42−, NO3− and NH4+) and Ca2+ were the dominant WSIIs in PM1.0, contributing about 89% to 95% of the total measured ions. The continental contributions of SO42−, K+, and Ca2+ accounted for more than 60% during the whole period, while Na+ and Cl− were mainly from marine sources. The source identification showed that airport emissions were a major source at the sampling site and significantly contributed to the levels of sulfate, nitrate, and ammonium. Agricultural activities were the dominant sources impacting visibility in spring, while airport emissions and secondary inorganic aerosols were the main components affecting visibility in summer. Therefore, improving atmospheric visibility in coastal airport areas should focus on reducing the precursors of secondary particulates and reducing biomass-burning activities.

Association between gut microbiota, plasma metabolites, and ovarian cancer: A Mendelian randomization study.

Numerous studies have demonstrated a correlation between alterations in gut microbiota (GM) and levels of body metabolites in ovarian cancer (OC). However, the specific causal relationships underlying these associations remain unclear. This study utilized summary statistics of GM from the MiBioGen consortium, along with an unprecedented dataset comprising 1091 blood metabolites and 309 metabolite ratios from the UK Biobank, in conjunction with OC data from the FinnGen Consortium R9 release. We conducted bidirectional Mendelian randomization (MR) analyses to investigate the causal relationships between GM and OC. Additionally, a two-step MR approach was employed to identify potential mediating metabolites. Our analysis revealed significant associations between 6 specific microbiota taxa and OC. Furthermore, we identified several plasma metabolites that act as mediators of the association between GM and OC. In the two-step MR analysis, we observed a negative correlation between 4-methoxyphenol sulfate and pregnenetriol disulfate levels with OC. The genus Lachnospiraceae UCG008 potentially increases the risk of OC by decreasing 4-methoxyphenol sulfate levels, while the genus Howardella may elevate the risk of OC by reducing pregnenetriol disulfate levels, with mediation proportions of 22.35% and 4.23%, respectively. Additionally, levels of dilinoleoyl-GPE (18:2/18:2) and N-acetylkynurenine (2) were positively correlated with OC. The inhibitory effect of the genus Ruminococcus 1 on OC may be mediated through 1,2-dilinoleoyl-GPE (18:2/18:2) and N-acetylkynurenine (2), with mediation proportions of 10.15% and 11.32%, respectively. Our findings highlight the complex relationship among GM, plasma metabolites, and OC. The identified associations and mediation effects offer valuable insights into potential therapeutic approaches targeting GM for the management of OC.

Models incorporating physical, laboratory and gut metabolite markers can be used to predict severe hepatic steatosis in MAFLD patients.

Metabolic-associated fatty liver disease (MAFLD) induced-severe hepatic steatosis poses significant health risks. Early prediction of this condition is crucial for prompt intervention. Short-chain fatty acids (SCFAs) and tryptophan are gut metabolites correlated with MAFLD pathogenesis in the gut-liver axis. This study aims to construct prediction models for severe hepatic steatosis by including SCFAs and tryptophan metabolites. This study enrolled 83 participants from the outpatient department in 2023. Physical measurements, serum metabolic and inflammatory markers, metabolites of serum SCFAs and tryptophan were collected. Severe hepatic steatosis was diagnosed using vibration-controlled transient elastography and abdominal sonography. All 40 (48.2%) participants diagnosed with severe hepatic steatosis had MAFLD, while approximately three-quarters of those without severe hepatic steatosis had MAFLD. In comparison to the non-severe hepatic steatosis group, individuals with severe hepatic steatosis exhibited higher levels of waist and arm circumference, serum triglyceride (TG), and lower levels of serum high-density lipoprotein cholesterol (HDL-C) and AST/ALT ratio. They also had higher serum levels of lipopolysaccharide-binding protein, isovaleric acid, and propionic acid, and lower levels of 3-methylvaleric acid, indole-3-propionic acid, and indoxyl sulfate. Models incorporating these markers predicted severe hepatic steatosis. One model additionally included waist circumference and triglyceride-glucose index, while the other incorporated arm circumference and TG/HDL-C ratio. The area under the curve reached 0.958 and 0.938, respectively (p < 0.001). SCFAs and tryptophan metabolites are valuable in predicting severe hepatic steatosis. Further research is needed to investigate the roles of these metabolites in MAFLD.

Mass spectrometry-based metabolomics reveals metabolism of molnupiravir may lead to metabolic disorders and hepatotoxicity.

Molnupiravir (MO) is a pyrimidine nucleoside anti-SARS-CoV-2 drug. MO treatment could cause mild liver injury. However, the underlying mechanism of MO-induced liver injury and the metabolic pathway of MO in vivo are unclear. In this study, metabolomics analysis and molecular biology methods were used to explore these issues. Through metabolomics analysis, it was found that the homeostasis of pyrimidine, purine, lysophosphatidylcholine (LPC), and amino acids in mice was destroyed after MO treatment. A total of 80 changed metabolites were detected. Among these changed metabolites, 4-ethylphenyl sulfate, dihydrouracil, and LPC 20:0 was related to the elevation of alkaline phosphatase (ALP), interleukin-6 (IL6), and nuclear factor kappa-B (NF-κB). The levels of 4-ethylphenyl sulfate, dihydrouracil, and LPC 20:0 in plasma were positively correlated with their levels in the liver, suggesting that these metabolites were associated with MO-induced liver injury. MO treatment could increase NHC and cytidine levels, activate cytidine deaminase (CDA), and increase LPC levels. CDA and LPC could increase the mRNA expression level of toll-like receptor (TLR). The current study indicated that the elevation of hepatic TLR may be an important reason for MO leading to the liver injury.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.MethodsTo investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).ResultsOur analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.ConclusionsOur comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

The overlooked salt: Impact of dark septate endophytes on alfalfa at varying sodium sulfate levels

Sodium sulfate (Na2SO4) is one sodium salt extensively found in saline soils; in certain regions, it is the dominant salt present. Dark septate endophytes (DSE) are competent in enhancing plants’ resistance to stressed environments. Nevertheless, little is known about the role of DSE in enhancing plant tolerance to Na2SO4. This study examined DSE growth and its impacts on alfalfa plants exposed to varying Na2SO4 concentrations (0%, 0.15%, 0.3%, and 0.45% (w/w)). Our findings revealed that DSE can thrive even in salt-stress environments. On the 8th day of cultivation, their biomass reached the highest level under 0.45% salt concentration. Moreover, DSE successfully colonized alfalfa roots and significantly enhanced plant growth and development across the various salt gradients. Notably, DSE made the highest contribution 68% to the total biomass of alfalfa at 0.45% salt concentration. Meanwhile, DSE significantly decreased the presence of root’s Na+ across varying salt gradients. Additionally, DSE significantly increased catalase (CAT) activity at salt concentrations of 0.3% and 0.45%. Our study also revealed strong positive correlations of plant biomass with the root index, root’s K+ content, and K+/Na+ ratio, and strong negative correlations of plant biomass with root’s Na+ content and soil’s Na+ and SO42− contents. Structural equation modeling (SEM) demonstrated that DSE indirectly enhanced plant’s shoot biomass under various salt stresses via increasing root length, decreasing root’s Na+ content, and raising CAT activity, while salt indirectly reduced plant’s shoot weight via reducing root length or increasing root’s Na+ content or exerted a direct negative effect on plant shoot biomass. Thus, DSE are instrumental in bolstering the salt tolerance of plants, which holds strategic importance for the management of saline-alkali soils.

Oral low-dose rapamycin treatment prevents aortic aneurysms in marfan mice

Abstract Background/Introduction Marfan syndrome (MFS) is a hereditary connective tissue disorder caused by fibrillin-1 (FBN1) gene mutations. Life-threatening complications are cardiovascular, e.g. thoracic aortic aneurysms and dissections. The pathophysiological cause is the increased release of transforming growth factor β-1 (TGF-β1) from the FBN1-deficient extracellular matrix (ECM) and structural disintegrity. Overactivation of the mechanistic target of rapamycin (mTOR) pathway has been demonstrated in the murine mgR/mgR model of MFS. Short-term administration of rapamycin significantly reduced aortic aneurysm formation and increased the life span in these mice. Purpose To assess the effect of an early continuous oral low-dose rapamycin treatment on the aortic aneurysm formation in the FBN1 hypomorphic mgR/mgR mouse model. Methods Male and female 3-4 week-old mgR/mgR mice were orally administered vehicle or rapamycin through diet (8mg/kg/KG) and sacrificed after 11 weeks. Rapamycin concentration was measured by liquid chromatography-mass spectrometry in whole blood. Aortic diameter was studied using echocardiography. Histopathological and immunofluorescence analyses were performed using aortic tissue sections and techniques. Results Blood rapamycin concentration following oral administration remained below detection level. Rapamycin normalized the aortic wall thickness and the diameter in female mgR/mgR mice to levels of the littermate control mice but not in male mgR/mgR mice. The circumferentially distributed elastin fibres remained significantly intact in sections of the ascending aorta of female mice. Echocardiography revealed that rapamycin-treated female mice stayed below a cut-off value for aortic aneurysms of 2 mm inner aortic diameter eight weeks after starting therapy. In contrast, vehicle-treated female animals already exceeded this value after five weeks. In female but not in male mice, the abundance of the mTOR downstream target phosphorylated ribosomal protein S6 was effectively suppressed by low-dose rapamycin up to levels detected in control animals. At the same time, extracellular matrix proteins like the proteoglycan aggrecan (ACAN) and the related chondroitin sulfate were significantly decreased in female mice. The abundance of ADAMTS5 transglutaminase-2 and xylosyltransferase-1, key enzymes involved in the turnover of proteoglycans and biosynthesis of glycosaminoglycan chains, was improved by the rapamycin treatment in female mice. No decrease in mTOR activity could be detected in male mgR/mgR animals. Here, the ACAN and chondroitin sulphate levels also remained at the level of the vehicle-treated animals. Conclusions Chronic low-dose rapamycin treatment reduced aneurysm formation only in female mgR/mgR mice, since the dose was too low for male mgR/mgR mice, by affecting the composition and organization of key ECM components essential for maintaining aortic homeostasis and mechanical properties.

Carbonic anhydrase-mediated phosphogypsum degradation and enhanced CO2 sequestration: a promising sustainable strategy for biological resource utilization of phosphogypsum.

This study continues our previous investigation of the intrinsic degradation of phosphogypsum (PG) by indigenous microorganisms on amending adequate nutrients. We aim to unravel the intricate mechanisms involved in PG biotransformation by a bacterial consortium. We isolated and characterized seven multi-metal-resistant bacterial strains from a nutrient-amended PG-contaminated microcosm and identified them through 16S rRNA gene sequencing. Primarily aerobic, Gram-positive chemolithotrophs, these strains demonstrated significant heavy metal uptake and PG degradation potential. Further analysis revealed that all strains produced carbonic anhydrase (CA), while six also produced urease, which may facilitate microbial-induced carbonate precipitation. Microstructural and elemental analysis using scanning electron microscopy-energy-dispersive X-ray and X-Ray Diffraction (XRD) confirmed the PG bio-transformation, indicating substantial increases in carbonate concentrations and reductions in sulfate levels. The consortium, composed of seven urease- and CA-producing bacterial strains, effectively degraded PG, transforming it from an acidic to an alkaline state and significantly enhancing CO2 sequestration.

Maternal Obesity and Differences in Child Urine Metabolome.

Background/objective: Approximately one-third of pregnant individuals in the U.S. are affected by obesity, which can adversely impact the in utero environment and offspring. This study aimed to investigate the differences in urine metabolomics between children exposed and unexposed to maternal obesity. Methods: In a study nested within a larger pregnancy cohort of women-offspring pairs, we measured untargeted metabolomics using liquid chromatography-mass spectrometry in urine samples from 68 children at 4-8 years of age. We compared metabolite levels between offspring exposed to maternal obesity (body mass index [BMI] ≥ 30.0 kg/m2) vs. unexposed (maternal BMI 18.5-24.9 kg/m2) and matched them on covariates, using two-sample t-tests, with additional sensitivity analyses based on children's BMI. This study reports statistically significant results (p ≤ 0.05) and potentially noteworthy findings (fold change > 1 or 0.05 < p < 0.15), considering compounds' involvement in common pathways or similar biochemical families. Results: The mean (SD) maternal age at study enrollment was 28.0 (6.3) years, the mean child age was 6.6 (0.8) years, 56% of children were male, and 38% of children had a BMI in the overweight/obese range (BMI ≥ 85th percentile). Children exposed to maternal obesity had lower levels of 5-hydroxyindole sulfate and 7-hydroxyindole sulfate and higher levels of secondary bile acids. Phenylacetic acid derivatives were lower in offspring exposed to obesity and in offspring who had a current BMI in the overweight/obese range. Exposure to maternal obesity was associated with lower levels of androgenic steroid dehydroepiandrosterone sulfate (DHEA-S). Conclusions: In this preliminary study, children exposed to maternal obesity in utero had differences in microbiome-related metabolites in urine suggestive of altered microbial catabolism of tryptophan and acetylated peptides. Some of these differences were partially attributable to the offspring's current BMI status. This study highlights the potential of urine metabolomics to identify biomarkers and pathways impacted by in utero exposure to maternal obesity.

Enhancing Sleep and Reducing Occupational Stress Through Forest Therapy: A Comparative Study Across Job Groups.

The coronavirus disease-2019 (COVID-19) pandemic radically shifted occupational patterns, leading to increased telecommuting and related stressors. Healthcare providers, among the most impacted group, faced heightened risks and workplace changes. Our study examined the efficacy of forest therapy in alleviating work-induced stress across various professions, exploring the need for profession-specific stress-relief strategies in the post-pandemic workplace. To examine the impact of COVID-19 on professionals, 62 participants were recruited, consisting of 20 healthcare providers, 21 information technology (IT) specialists, and 21 teachers. Instruments such as Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale, along with salivary tests for cortisol and melatonin, were used to assess the participants' sleep and stress levels. A specialized forest healing program was implemented among these participants. Data analysis was conducted using SPSS Win Ver. 22.0, utilizing paired t-tests and a repeated measures analysis of variance. Significant improvements were observed in the participants' sleep metrics, depression scales, and stress levels after the forest healing program. Physiological measures indicated an increase in melatonin and a decline in cortisol and dehydroepiandrosterone sulfate levels, with only cortisol changes being statistically significant. Teachers, participating during school vacations, exhibited minimal stress-related physiological changes. Overall, the program demonstrated widespread health benefits regardless of occupation or gender. This study showed that forest therapy reduced stress equally across professions, including healthcare providers, IT specialists, and teachers. Individual physiological responses may play a greater role in stress relief than the specific occupation.

Refining habitat selection for sulfate-reducing bacteria: Evaluating suitability and adaptability for sulfate-metal wastewater treatment during anaerobic-to-aerobic transitions

Inoculating sulfate-reducing bacteria (SRB) habitats offers an eco-friendly method for treating sulfate-metal laden wastewater, characterized by high sulfate levels, low pH, and elevated heavy metals. This study optimizes source habitat selection of SRB by evaluating groundwater, sewage sludge, and lake sediment, focusing on their suitability and adaptability to aerobic-anaerobic transitions in industrial settings. Sewage sludge, with its slightly acidic pH, reducing environment, and high nutrient levels (Total organic carbon: 207.53 g kg−1, Total nitrogen: 47.12 g kg−1), provides robust SRB potential, as supported by its highest diversity index. However, heavy metals and polycyclic aromatic hydrocarbons pose application challenges. All habitats effectively reduced metal concentrations anaerobically, with Cu removal reaching 95%–99%, and groundwater achieved the highest chemical oxygen demand reduction (63.6%) aerobically. Sludge and sediment showed high biomass and extracellular polymeric substances (EPS) accumulation, while groundwater's nucleic acid-rich EPS enhanced metal immobilization, resulting in stable residual metal forms but with potential remobilization under oxidative conditions. Microbial analysis revealed that Proteobacteria and Firmicutes were key players during transitions, with the highest SRB abundance in groundwater. SRB composition varied across habitats, with Sedimentibacter (13.04%), Desulfovibrio (6.33%), and Desulfomonile (8.1%) dominating in groundwater, sludge, and sediment, respectively, during the anaerobic stage. Functional analysis highlighted sludge's persistence in sulfate reduction under aerobic conditions, while groundwater's limited nitrogen cycle involvement indicated broader biogeochemical limitations. Collectively, these findings highlight strengths and limitations of each habitat as SRB inoculum source, emphasizing the importance of tailored anaerobic-to-aerobic strategies for effective wastewater management.

Gut Microbiota and Metabolic Alterations Associated with Heart Failure and Coronary Artery Disease.

This study investigates the role of gut microbiota in cardiovascular diseases, with an additional focus on pro-atherogenic metabolites. We use advanced network analysis and machine learning techniques to identify key microbial features linked to coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF). This cross-sectional study included 189 participants divided into three groups: coronary artery disease (n = 93), heart failure with reduced ejection fraction (n = 43), and controls (n = 53). Assessments included physical exams, echocardiography, dietary surveys, blood analysis, and fecal analysis. Gut microbiota composition was analyzed using next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Statistical analysis methods for testing hypotheses and correlations, alpha and beta-diversity analyses, co-occurrence networks, and machine learning were conducted using Python libraries or R packages with multiple comparisons corrected using the Benjamini-Hochberg procedure. Significant gut microbiota alterations were observed, with higher Bacillota/Bacteroidota ratios in CAD and HFrEF groups compared to controls (p < 0.001). Significant differences were observed in α-diversity indices (Pielou, Chao1, Faith) between disease groups and controls (p < 0.001). β-diversity analyses also revealed distinct microbial profiles (p = 0.0015). Interestingly, trimethylamine N-oxide (TMAO) levels were lower in CAD and HFrEF groups compared to controls (p < 0.05), while indoxyl sulfate (IS) levels were comparable between the study groups. Co-occurrence network analysis and machine learning identified key microbial features linked to these conditions, highlighting complex interactions within the gut microbiota associated with cardiovascular disease.