Absorption and Metabolism of Urolithin A and Ellagic Acid in Mice and Their Cytotoxicity in Human Colorectal Cancer Cells.

Background: Ellagic acid is a natural polyphenol compound found in pomegranates, walnuts, and many berries. It is not easily absorbed, but it could be metabolized to urolithins by the gut microbiota. Urolithin A, one of the ellagic acid metabolites, has been proved to prolong the lifespan of C. elegans and increases muscle function of mice. The purpose of this current study was to analyze the absorption and metabolites of urolithin A and ellagic acid in mice and the anticancer effects of urolithin A, urolithin B, and ellagic acid in colorectal cancer cells. Methods: Urolithin A and urolithin B were synthesized and analyzed by HPLC and NMR. A pharmacokinetic study of urolithin A was performed in mice by analyzing urolithin A and its metabolites in urines. Absorption and biotransformation of ellagic acid were also studied in mice by analyzing the plasma, liver, and feces. The cytotoxicity of urolithin A, urolithin B, and ellagic acid was assayed in SW480, SW620, HCT 116, and HT-29 cells. Results: Urolithin A and urolithin B were synthesized and purified to reach 98.1% and 99% purity, respectively, and the structures were identified by NMR. In urolithin A intake analysis, urolithin A was only detectable at 3 h, not at 6-24 h; it suggested that urolithin A was rapidly metabolized to some unknown metabolites. Using UPLC-MS/MS analysis, the metabolites might be urolithin A 3-O-glucuronide, urolithin A 3-sulfate, and urolithin A-sulfate glucuronide. After feeding mice with ellagic acid for consecutive 14 days, ellagic acid contents could be detected in the fecal samples, but not in plasma and liver, and urolithin A was not detected in all samples. It suggests that ellagic acid is not easily absorbed and that the biotransformation of ellagic acid to urolithin A by intestinal flora might be very low. From the cytotoxicity assay, it was found that there was anticancer effect in urolithin A and urolithin B but not in ellagic acid. In contrast, ellagic acid promoted the proliferation of SW480 and SW620 cells.

Value of Doppler Ultrasonography in Assessing the Efficacy of Diabetic Retinopathy: A Retrospective Analysis.

Objective: To investigate the value of Doppler ultrasound in evaluating the efficacy of diabetic retinopathy. Methods: A retrospective analysis was conducted on 90 hospitalized patients with type 2 diabetes from January 2019 to January 2020. The patients were divided into two groups: 34 cases without retinopathy and 56 cases with diabetic retinopathy. Clinical data and Doppler ultrasonography results were collected and analyzed to evaluate the value of Doppler ultrasound. Results: After treatment, various indicators, including blood glucose, HbA1c, FPG, 2hFPG, HOMA-IR, and FINS, showed significant improvement in both groups (P < .05). There was no significant difference before and after treatment (P > .05). Before treatment, the retinopathy group exhibited significantly different central artery parameters: PSA (8.35 ± 1.08), EDV (5.80±0.62), RI (1.53 ± 0.25), compared to patients without retinopathy: PSA (13.61 ± 1.80), EDV (7.23 ± 0.51), RI (0.85 ± 0.02) (t = 12.019, 11.631, 11.461, P = .01, .01, .00), respectively. After treatment, the central artery parameters improved in both groups. The retinopathy group showed PSA (10.44 ± 0.26), EDV (6.84 ± 0.85), RI (1.01 ± 0.04), while patients without retinopathy exhibited PSA (15.13 ± 1.20), EDV (8.50 ± 0.80), RI (0.71 ± 0.08) (t = 15.94, 12.01, 13.32, P = .01, .01, .01), respectively. Similarly, before treatment, the retinopathy group had different central artery parameters: PSA (30.35 ± 5.15), EDV (8.85 ± 1.67), RI (1.53 ± 0.25), compared to patients without retinopathy: PSA (34.41 ± 5.20), EDV (11.34 ± 2.56), RI (0.88 ± 0.15) (t = 12.108, 11.542, 11.57, P = .01, .01, .01), respectively. After treatment, the central artery parameters improved in both groups. The retinopathy group showed PSA (33.26 ± 4.27), EDV (9.37 ± 1.86), RI (0.98 ± 0.35), while patients without retinopathy exhibited PSA (36.15 ± 4.24), EDV (13.51 ± 2.13), RI (0.76 ± 0.23) (t = 13.84, 12.14, 10.11, P = .01, .01, .01), respectively. Conclusions: Color Doppler ultrasound monitoring of fundus hemodynamic parameters can accurately reflect the changes in blood vessels in diabetic eyes. It provides real-time and objective evaluation of fundus hemodynamic indexes. This technology demonstrates high repeatability and simple operation, making it valuable for the non-invasive detection of early retinopathy.

Insights into simultaneous nitrogen and phosphorus removal in biofilm: The overlooked comammox Nitrospira and the positive role of glycogen-accumulating organisms.

Simultaneous nitrogen and phosphorus removal (SNPR) biofilm system is an effective wastewater treatment process. However, the understanding on the mechanism of functional microorganisms driving SNPR is still limited, especially the role of complete ammonia oxidation (comammox) Nitrospira and glycogen-accumulating organisms (GAO). In this study, a sequencing batch biofilm reactor (SBBR) performing SNPR was operated for 249 d. Based on the 16S rRNA gene, comammox amoA amplicon sequencing, metagenomics and batch experiment, we found that comammox Nitrospira was the main ammonia-oxidizing microorganisms (AOM) and provided nitrite for anaerobic ammonia oxidation (anammox) bacteria (AnAOB). Besides, GAO was dominated by the bacteria of genus Defluviicoccus and played a primary role in reducing nitrate rather than nitrite. Fluorescent in situ hybridization (FISH) analysis confirmed that Nitrospira was enriched in the inner layer of the biofilm. Thus, we put forward a novel insight into the mechanism of SNPR biofilm system. Comammox Nitrospira was responsible for nitrite and nitrate production in the inner biofilm, and AnAOB consumed the produced nitrite during the anammox process. While GAO reduced nitrate to nitrite and polyphosphate-accumulating organisms (PAO) converted nitrite to dinitrogen via denitrifying phosphorus removal in the outer biofilm. These findings provide a new understanding in SNPR biofilm system.

Composition and Bioactivity of a Modified Huang-Lian-Jie-Du Decoction.

Background: Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods: We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results: HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-α treatment increased the expression of certain cytokines, including IL-1ß, IL-8, M-CSF, and TGF-ß2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-ß2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity.

Circular RNA circ-RCCD promotes cardiomyocyte differentiation in mouse embryo development via recruiting YY1 to the promoter of MyD88.

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non-coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ-RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ-RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial-specific markers CTnT, Mef2c, and GATA4. Next, we found that circ-RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ-RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ-RCCD inhibited nuclear translocation of YY1. These results reported that circ-RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ-RCCD as a target for the treatment of CHD.

The anticancer effects of cyanidin 3-O-glucoside combined with 5-fluorouracil on lung large-cell carcinoma in nude mice.

The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1ß, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-ß, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.

Feammox process driven anaerobic ammonium removal of wastewater treatment under supplementing Fe(III) compounds.

Ammonium removal in wastewater treatment plants demands large quantities energy input, such as aeration for wastewater and the addition of organics for nitrate reduction. Anaerobic ammonium oxidation coupled to Fe(III) reduction, called Feammox process play a crucial role in natural nitrogen cycle, which has been rarely investigated in the field of wastewater treatment. Besides, Iron-reducing bacteria (FeRB) as function bacteria of Feammox could transfer electrons to iron oxide by oxidizing organics. The possibility of anaerobic ammonium removal coupled with organics should be investigated to assess the potential of Feammox process for conventional wastewater treatment. In this study, five Fe(III) compounds, Fe2O3, Fe3O4, Fe(OH)3, Citrate-Fe and pyrite were supplemented to investigate the effect of iron oxides on ammonium removal in serum bottles with working volume of 100 mL. It was found that ammonium removal efficiency of the Fe2O3 group was the highest. To simulate wastewater treatment process in sewage treatment plant, three Up-flow anaerobic sludge blanket reactors with volume of 250 mL adding Fe2O3 were applied with influent of ammonium and carbon sources. It was found that the organics significantly inhibited the ammonium removal by Feammox process. This was attributed to that carbon sources and ammonium could be used as electron donors for Fe(III) reduction. In addition, this nitrogen removal was also likely related with the iron cycle, i.e., Fe(III) reduction with ammonium oxidation and Fe(II) oxidation with nitrate/nitrite reduction. This study provides a promising alternative technology for anaerobic ammonium removal in wastewater treatment. Optimizing nitrogen removal and carbon sources applied in conventional wastewater plants are required in future.

A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Background: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. Methods: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. Results: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Conclusions: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

Expression and Possible Significance of ACE2 in the Human Liver, Esophagus, Stomach, and Colon.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the key receptor of SARS coronavirus that plays a key role in the pathogenesis of SARS. It is known that ACE2 mRNA can be expressed in most organs. However, the protein expression of ACE2 is not clear yet. To explore the role of ACE2 as a precipitating factor in digestive organ damage in COVID-19, this study investigated the expression of ACE2 protein in the human liver, esophagus, stomach, and colon. The result showed that ACE2 can be expressed in the liver, esophagus, stomach, and colon, which suggests SARS-CoV-2 may enter the digestive system through ACE2 and cause liver damage and gastrointestinal damage. It is hoped that the result of the study will provide a new strategy for the prevention and treatment of digestive organ damage under COVID-19.

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum.

Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells' proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.

Electrostimulation enhanced ammonium removal during Fe(III) reduction coupled with anaerobic ammonium oxidation (Feammox) process.

Ammonium removal in wastewater treatment plants requires a large number of energy input, such as aeration and the addition of organics. Alternative, more economical technologies for nitrogen removal from wastewater are required. This study comprehensively investigated the feasible of microbial electricity coupled with Fe(III) reduction promoting the anaerobic ammonium removal. It was found that electrostimulation coupled with Fe(III) reduction (bioelectrochemical systems-Fe(III) (BES-Fe(III)) reactor) enhanced the anaerobic ammonium removal by 50.38% and 38.8% compared with the BES reactor and Fe(III) reactor, respectively. The ammonium removal rate reached the highest value of 80.62 ± 0.26 g N m-3·d-1 in the Fe(III)-BES reactor comparable to conventional wastewater treatment plants (WWWTPs). The improvement of ammonium removal might be the synergistic effect of BES and Feammox process on reaction process and microorganisms. Firstly, the addition of Fe2O3 could improve the electrochemical characteristics by enriching iron-reducing bacterial (FeRB). Secondly, the improved ammonium removal could be due to nitrite generated from Feammox process driving the anodic ammonium oxidation. Additionally, the ammonium removal improvement might be the effect of BES on the Fe2+ leaching so as to accelerate the Fe (II)/Fe(III) cycle. In agreement, higher abundance of FeRB and iron-oxidizing bacteria was detected in the Fe(III)-BES reactor. This study provides a lower energy consumption and operational cost technology compared with the conventional partial nitrification/denitrification, which was more than 800 times less than for the conventional wastewater treatment.

Potential Protective Effect of Dietary Intake of Non-α-Tocopherols on Cellular Aging Markers Mediated by Tumor Necrosis Factor-α in Prediabetes: A Cross-Sectional Study of Chinese Adults.

It remains unknown how different glucose tolerance status affects the relationships between dietary intake of different tocopherol isoforms (α-, ß-, γ-, and δ-tocopherol) and cellular aging, oxidative stress, and inflammatory markers. The authors conducted a cross-sectional study among 582 Chinese adults with different glucose tolerance status to explore the association between dietary intake of different tocopherol isoforms and cellular aging, oxidative stress, and inflammatory markers. The inverse correlations between non-α-tocopherols and tumor necrosis factor-alpha (TNF-α) varied substantially across different glucose tolerance status, with the strongest observed in prediabetes (r = -0.33 for ß-/γ-tocopherol, r = -0.37 for δ-tocopherol, p < 0.01), followed by normal glucose tolerance (NGT). While such correlations were abolished in established diabetes. Furthermore, within prediabetes, the strongest inverse correlations between non-α-tocopherols and TNF-α were observed in impaired fasting glucose (IFG) (r = -0.42 for ß-/γ-tocopherol, r = -0.55 for δ-tocopherol, p < 0.01), while such correlations were significantly attenuated in individuals with impaired glucose tolerance (IGT) and IFG+IGT. And mediation model analysis displayed that TNF-α mediated the protective effect of non-α-tocopherols on leukocyte telomere length and mitochondrial DNA copy number, which was uniquely observed in prediabetes, while such mediation effect was statistically nonsignificant in NGT and established diabetes. In conclusion, our findings indicate that dietary intake of non-α-tocopherols might protect against cellular aging markers mediated by TNF-α in prediabetes. Individuals with prediabetes, especially for IFG, might benefit from increasing dietary intake of non-α-tocopherol in alleviating inflammation and cellular aging, which might provide a new dietary avenue for delaying diabetes onset.

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid.

SCOPE: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). METHODS AND RESULTS: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of TαMCA, TßMCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. CONCLUSION: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM.

Norfloxacin-induced effect on enhanced biological phosphorus removal from wastewater after long-term exposure.

In this study, long-term experiments were performed under synthetic wastewater conditions to evaluated the potential impacts of norfloxacin (NOR) (10, 100 and 500 µg/L) on enhanced biological phosphorus removal (EBPR). Experimental result showed that long-term exposure to 10 µg/L NOR induced negligible effects on phosphorus removal. The presence of 100 µg/L NOR slightly decreased phosphorus removal efficiency to 94.41 ± 1.59 %. However, when NOR level further increased to 500 µg/L, phosphorus removal efficiency was significantly decreased from 97.96 ± 0.8 5% (control) to 82.33 ± 3.07 %. The mechanism study revealed that the presence of 500 µg/L NOR inhibited anaerobic phosphorus release and acetate uptake as well as aerobic phosphorus uptake during long-term exposure. It was also found that 500 µg/L NOR exposure suppressed the activity of key enzymes related to phosphorus removal but promoted the transformations of intracellular polyhydroxyalkanoate and glycogen. Microbial analysis revealed that that the presence of 500 µg/L NOR reduced the abundances of polyphosphate accumulating organisms but increased glycogen accumulating organisms, as compared the control.

Sex-Specific Negative Association between Iron Intake and Cellular Aging Markers: Mediation Models Involving TNFα.

BACKGROUND: Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. However, epidemiological research on dietary iron intake and cellular aging markers is scarce. The aim of this study was to explore the relationship between dietary iron intake and cellular aging markers and to investigate whether tumor necrosis factor-α (TNFα) mediated this relationship. METHODS: We conducted a cross-sectional analysis with a total of 467 subjects. Detailed dietary data were obtained using 24 h food recalls. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using real-time PCR assay. The association between dietary iron intake and cellular aging markers and TNFα and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Simple mediation models were generated to examine whether TNFα mediated the association between iron intake and cellular aging markers using PROCESS macro Version 3.3. RESULTS: The study population contained more women than men, but their basic demographic and metabolic characteristics did not differ. After adjusting for age, LTL was the same for men and women, while mtDNAcn was lower in men. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. Moreover, iron intake was positively associated with TNFα in both women and men but positively associated with SOD only in men. Path modeling showed that TNFα significantly mediated the indirect detrimental effect of iron intake on LTL only in women; in men, mediation of the indirect effect of iron intake on mtDNAcn by TNFα did not reach significance. CONCLUSIONS: The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNFα. Consequently, when dietary iron intake and iron supplementation is recommended, the effects of iron imbalance on genomic stability and cellular aging markers must be considered.

Free nitrous acid-based nitrifying sludge treatment in a two-sludge system obtains high polyhydroxyalkanoates accumulation and satisfied biological nutrients removal.

A novel strategy to achieve substantial polyhydroxyalkanoates (PHA) accumulation in waste activated sludge (WAS) was developed, which was conducted in a two-sludge system consisted of an anaerobic/anoxic/oxic reactor (AAO-SBR) and a nitrifying reactor (N-SBR), where the nitrifying-sludge was treated by free nitrous acid (FNA). Initially, 0.98 ±â€¯0.09 and 1.46 ±â€¯0.10 mmol-c/g VSS of PHA were respectively determined in the control-SBR and AAO-SBR. When 1/16 of nitrifying sludge was daily treated with 1.49 mg N/L FNA for 24 h, ∼46.5% of nitrite was accumulated in the N-SBR, ∼2.43 ±â€¯0.12 mmol-c/g VSS of PHA was accumulated in WAS in AAO-SBR without deteriorating nutrient removal. However, nutrient removal of control-SBR was completely collapsed after implementing the same FNA treatment. Further investigations revealed that the activity and abundance of nitrite oxidizing bacteria (NOB) was decreased significantly after FNA treatment. Finally, sludge with high PHA level to generate more methane was confirmed.

The roles of free ammonia (FA) in biological wastewater treatment processes: A review.

Free ammonia (FA) can pose inhibitory and/or biocidal effects on a variety of microorganisms involved in different biological wastewater treatment process, which is widely presented in wastewater treatment plants (WWTPs) due to the high levels of ammonium in the systems. This review article gives the up-to-date status on several essential roles of FA in biological wastewater treatment processes: the impacts of FA, mechanisms of FA roles, modeling of FA impacts, and implications of FA for wastewater treatment. Specifically, the impacts of FA on both wastewater and sludge treatment lines were firstly summarized, including nitrification, denitrification, anaerobic ammonium oxidation (Anammox), enhanced biological phosphorus removal and anaerobic processes. The involved mechanisms were then analyzed, which indicated FA inhibition can slow specific microbial activities or even reconfigure the microbial community structure, likely due to negative impacts of FA on intracellular pH, specific enzymes and extracellular polymeric substances (EPS), thus causing cell inactivation/lysis. Mathematical models describing the impact of FA on both wastewater and sludge treatment processes were also explored to facilitate process optimization. Finally, the key implications of FA were identified, that is FA can be leveraged to substantially enhance the biodegradability of secondary sludge, which would further improve biological nutrient removal and enhance renewable energy production.

Free ammonia-based pretreatment enhances phosphorus release and recovery from waste activated sludge.

The recovery of phosphorus from waste activated sludge (WAS) was usually at low levels due to low phosphorus release. This study presents a novel, cost-effective and eco-friendly pretreatment method, e.g., using free ammonia (FA) to pretreat WAS, to enhance the phosphorus release from WAS. Experimental results showed that the phosphorus release from WAS was significantly increased after FA pretreatment at up to 189.4 mg NH3-N L-1 for 24 h, under which the released PO43--P (i.e. 101.6 ±â€¯6.7 mg L-1) was higher than that pH 9 (i.e. 62.6 ±â€¯4.54 mg L-1) and control (without pH and FA pretreatment) (i.e. 15.1 ±â€¯1.86 mg L-1). More analysis revealed that the FA induced improvement in phosphorus release could be attributed to the disintegration of extracellular polymeric substances (EPS) and cell envelope of sludge cells. Moreover, the released phosphorus recovered as magnesium ammonium phosphate (MAP) was confirmed. The findings reported may guide engineers to develop an economic and practical strategy to enhance resources and energy recovery from WAS.

Effect of acetate to glycerol ratio on enhanced biological phosphorus removal.

Enhanced biological phosphorus removal (EBPR) is a sustainable and promising technology for phosphorus removal from wastewater. The efficiency of this technology, however, is often discounted due to the insufficient carbon sources in influent. In this work, the effect of acetate to glycerol ratio on the EBPR performance was evaluated. The experimental results showed when the ratio of acetate to glycerol decreased from 100/0% to 50/50%, the EBPR efficiency increased from 90.2% to 96.2%. Further decrease of acetate to glycerol ratio to 0/100% decreased the efficiency of EBPR to 30.5%. Fluorescence in situ hybridization analysis demonstrated appropriate increase of glycerol benefited to increase the relative abundance of phosphate accumulating organisms. Further investigation revealed the proper addition of glycerol increased the amount of polyhydroxyalkanoates synthesis, and then produced sufficient energy for oxic luxury phosphorus in the subsequent oxic phase.

Free nitrous acid-based nitrifying sludge treatment in a two-sludge system enhances nutrient removal from low-carbon wastewater.

A new method to enhance nutrient removal from low carbon-wastewater was developed. The method consists of a two-sludge system (i.e., an anaerobic-anoxic-oxic reactor coupled to a nitrifying reactor (N-SBR)) and a nitrifying-sludge treatment unit using free nitrous acid (FNA). Initially, 65.1±2.9% in total nitrogen removal and 69.6±3.4% in phosphate removal were obtained without nitrite accumulation. When 1/16 of the nitrifying sludge was daily treated with FNA at 1.1mgN/L for 24h, ∼28.5% of nitrite was accumulated in the N-SBR, and total nitrogen and phosphate removal increased to 72.4±3.2% and 76.7±2.9%, respectively. About 67.8% of nitrite was accumulated at 1.9mgN/L FNA, resulting in 82.9±3.8% in total nitrogen removal and 87.9±3.5% in phosphate removal. Fluorescence in-situ hybridization analysis showed that FNA treatment reduced the abundance of nitrite oxidizing bacteria (NOB), especially that of Nitrospira sp.