Analysis of the regulatory mechanism of exogenous IAA-mediated tryptophan accumulation and synthesis of endogenous IAA in Chlorococcum humicola.

The activated sludge method is widely used for the treatment of phenol-containing wastewater, which gives rise to the problem of toxic residual sludge accumulation. Indole-3-acetic acid (IAA), a typical phytohormone, facilitates the microalgal resistance to toxic inhibition while promoting biomass accumulation. In this study, Chlorococcum humicola (C. humicola) was cultured in toxic sludge extract and different concentrations of IAA were used to regulate its physiological properties and enrichment of high value-added products. Ultimately, proteomics analysis was used to reveal the response mechanism of C. humicola to exogenous IAA. The results showed that the IAA concentration of 5 × 10-6 mol/L (M) was most beneficial for C. humicola to cope with the toxic stress in the sludge extract medium, to promote the activity of rubisco enzyme, to enhance the efficiency of photosynthesis, and, finally, to accumulate protein as a percentage of specific dry weight 1.57 times more than that of the control group. Exogenous IAA altered the relative abundance of various amino acids in C. humicola cells, and proteomic analyses showed that exogenous IAA stimulated the algal cells to produce more indole-3-glycerol phosphate (IGP), indole, and serine by up-regulating the enzymes. These precursors are converted to tryptophan under the regulation of tryptophan synthase (A0A383V983), and tryptophan can be metabolized to endogenous IAA to promote the growth of C. humicola. These findings have important implications for the treatment of toxic residual sludge while enriching for high-value amino acids.

The efficient capture of polysaccharides in Tetradesmus obliquus of indole-3-acetic acid coupling sludge extraction.

Polysaccharide is an important biomass of algae. The sludge extract is rich in organic substances, which can be used by algae for biomass growth and high-value biomass synthesis, but its organic toxicity has an inhibitory effect on algae. To overcome inhibition and improve polysaccharide enrichment, Tetradesmus obliquus was cultured with sludge extract with different indole-3-acetic acid (IAA) concentrations. Within 30 days of the culture cycle, T. obliquus showed in good condition at the IAA dosage content of 10-6 M, the maximum cell density and dry weight were respectively (106.78 ± 2.20) × 106 cell/mL and 2.941 ± 0.067 g/L while the contents of chlorophyll-a, chlorophyll-b, and carotenoid were 1.79, 1.91 and 2.80 times that of the blank group, respectively. The highest polysaccharide accumulation was obtained under this culture condition, reaching 533.15 ± 21.11 mg/L on the 30th day, which was 2.49 times that in the blank group. By FT-IR and NMR analysis, it was found that the polysaccharides of T. obliquus were sulfated polysaccharide with glucose and rhamnose as the main monosaccharides. Proteomic showed that the up-regulation of A0A383WL26 and A0A383WLM8 enhanced the light trapping ability, and A0A383WMJ2 enhanced the accumulation of NADPH. The up-regulation of A0A383WHD5 and A0A383WAY6 indicated that IAA culture could repair the damage caused by sludge toxicity, thus promoting the accumulation of biomass. The above findings provided new insights into the mechanism of sludge toxicity removal of T. obliquus and the enhancement of the polysaccharide accumulation effect under different concentrations of IAA.

Excessive composite pollution carbon sources enhance the bio-fertilizer efficiency of Tetradesmus obliquus: focused on cultivation period.

Microalgae can use carbon sources in sludge extract prepared from sludge. Moreover, the high concentration of CO2 and the large number of carbon sources in the liquid phase will promote microalgae growth and metabolism. In this experiment, Tetradesmus obliquus was cultivated with sludge extract at 30% CO2. Algae liquid (the name used to describe the fertilizer made in this research) was further prepared as lettuce fertilizer. The effect of different times of microalgae culture (10, 15, 20, 25, and 30 days) on the fertilizer efficiency of the algae liquid was evaluated by lettuce hydroponic experiments. The findings indicate that lettuce cultivated in algae liquid collected on the 15th and 30th days exhibited superior performance in terms of growth, antioxidant capacity, and nutritional quality. We analyzed the experimental results in the context of microalgae metabolic mechanisms, aiming to contribute experience and data essential for the development of industrial microalgae fertilizer production.

Protective role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells.

Background and Objectives: Triptolide (TP) is known to impair testicular development and spermatogenesis in mammals, but the mechanism of the side effects still needs to be investigated. The aim of the research is to confirm whether TP can cause autophagy in TM3 Leydig cells and the potential molecular pathway in vitro. Methods: TM3 Leydig cells are used to investigate the molecular pathway through Western blot, detection of apoptosis, transmission electron microscopy for autophagosomes and so on. Results: The data show that TP treatment resulted in the decreasing of the viability of TM3 cells due to the increased apoptosis. Treated with TP, the formation of autophagosomes, the decrease in P62, and the increase in the conversion of LC3-I to LC3-II suggested the induction of autophagy. The induction of autophagy has accompanied the activation of the mTOR/P70S6K signal pathway. The viability of the TM3 cells was further inhibited when they were co-treated with autophagy inhibitor, chloroquine (CQ). Conclusion: All these data suggest that autophagy plays a very important role in antagonizing TM3 cell apoptosis during the TP exposure.

Indole-3-acetic acid mediated removal of sludge toxicity by microalgae: Focus on the role of extracellular polymeric substances.

The use of indole-3-acid (IAA) as an additive aided in achieving the objectives of reducing sludge extract toxicity, increasing Tetradesmus obliquus biomass yield, and enhancing extracellular polysaccharide production. Proteomics analysis can unveil the microalgae's response mechanism to sludge toxicity stress. With 10-6 M IAA addition, microalgae biomass reached 3.426 ± 0.067 g/L. Sludge extract demonstrated 78.3 ± 3.2% total organic carbon removal and 72.2 ± 2.1% toxicity removal. Extracellular polysaccharides and proteins witnessed 2.08 and 1.76-fold increments, respectively. Proteomic analysis indicated that Tetradesmus obliquus directed carbon sources towards glycogen accumulation and amino acid synthesis, regulating pathways associated with carbon metabolism (glycolysis, TCA cycle, and amino acid metabolism) to adapt to the stressful environment. These findings lay the groundwork for future waste sludge treatment and offer novel insights into microalgae cultivation and extracellular polysaccharide enrichment in sludge.

Analysis of the mechanism of exogenous indole-3-acetic acid on the enrichment of d-glucose in Chlorococcum humicola cultured by sludge extracts.

Addressing problems of high organic toxicity in the wastewater treatment process, microalgae have been used to reduce the toxicity in sludge and to synthesize non-toxic and recoverable biomass of resources. Phytohormone is a core regulator of plant growth and current research has generally focused on their promotion of cell division and cell expansion. Effects of phytohormone on the enrichment mechanism of microalgae directional polysaccharides accumulation remain poorly elucidated. This study was carried out to investigate the effects of exogenous indole-3-acetic acid (IAA) on growth characteristics, biomass accumulation, and photosynthesis capacity of Chlorococcum humicola cultured in sludge extract and further find the d-glucose enrichment mechanism of it through proteomic. The results indicated that the optimal culture conditions were the 75 % sludge extract and 25 % selenite enrichment (SE) medium with 5 × 10-6 mol/L indole-3-acetic acid. Polysaccharides increased significantly from day 20 and accumulated to (326.59 ± 13.06) mg/L on day 30, in which the d-glucose proportion increased to 61.53 %. Most notably, proteomic tests were performed and found that the photosynthesis-related proteins including the differential proteins of photosystem electron transport, ATP and NADPH catalytic synthesis were significantly up-regulated. At the end of the path, three pathways of d-glucose enrichment with α-d-Glucose-1P as a precursor were summarized through indole-3-acetic acid activation on amylase, endoglucanase and Beta-glucosidase, etc. These results provide insights to explore the directed enrichment of biomass in Chlorococcum humicola by indole-3-acetic acid.

A Robust Squarate-Cobalt Metal-Organic Framework for CO2/N2 Separation.

The separation of CO2 from the industrial post-combustion flue gas is of great importance to reduce the increasingly serious greenhouse effect, yet highly challenging due to the extremely high stability, low cost, and high separation performance requirements for adsorbents under the practical operating conditions. Herein, we report a robust squarate-cobalt metal-organic framework (MOF), FJUT-3, featuring an ultra-small 1D square channel decorated with -OH groups, for CO2/N2 separation. Remarkably, FJUT-3 not only has excellent stability under harsh chemical conditions but also presents low-cost property for scale-up synthesis. Moreover, FJUT-3 shows excellent CO2 separation performance under various humid and temperature conditions confirmed by the transient breakthrough experiments, thus enabling FJUT-3 with adequate potentials for industrial CO2 capture and removal. The distinct CO2 adsorption mechanism is well elucidated by theoretical calculations, in which the hierarchical C···OCO2, C-O···CCO2, and O-H···OCO2 interactions play a vital synergistic role in the selective CO2 adsorption process.

Optimized Pore Nanospace through the Construction of a Cagelike Metal-Organic Framework for CO2/N2 Separation.

The development of metal-organic framework (MOF) adsorbents with a potential molecule sieving effect for CO2 capture and separation from flue gas is of critical importance for reducing the CO2 emissions to the atmosphere yet challenging. Herein, a cagelike MOF with a suitable cage window size falling between CO2 and N2 and the cavity has been constructed to evaluate its CO2/N2 separation performance. It is noteworthy that the introduction of coordinated dimethylamine (DMA) and N,N'-dimethylformamide (DMF) molecules not only significantly reduces the cage window size but also enhances the framework-CO2 interaction via C-H···O hydrogen bonds, as proven by molecular modeling, thus leading to an improved CO2 separation performance. Moreover, transient breakthrough experiments corroborate the efficient CO2/N2 separation, revealing that the introduction of DMA and DMF molecules plays a vital role in the separation of a CO2/N2 gas mixture.

Comparative Mitogenomic Analyses of Hydropsychidae Revealing the Novel Rearrangement of Protein-Coding Gene and tRNA (Trichoptera: Annulipalpia).

Gene rearrangement of the mitochondrial genome of insects, especially the rearrangement of protein-coding genes, has long been a hot topic for entomologists. Although mitochondrial gene rearrangement is common within Annulipalpia, protein-coding gene rearrangement is relatively rare. As the largest family in Annulipalpia, the available mitogenomes from Hydropsychidae Curtis, 1835 are scarce, and thus restrict our interpretation of the mitogenome characteristic. In this study, we obtained 19 novel mitogenomes of Hydropsychidae, of which the mitogenomes of the genus Arctopsyche are published for the first time. Coupled with published hydropsychid mitogenome, we analyzed the nucleotide composition evolutionary rates and gene rearrangements of the mitogenomes among subfamilies. As a result, we found two novel gene rearrangement patterns within Hydropsychidae, including rearrangement of protein-coding genes. Meanwhile, our results consider that the protein-coding gene arrangement of Potamyia can be interpreted by the tandem duplication/random loss (TDRL) model. In addition, the phylogenetic relationships within Hydropsychidae constructed by two strategies (Bayesian inference and maximum likelihood) strongly support the monophyly of Arctopscychinae, Diplectroninae, Hydropsychinae, and Macronematinae. Our study provides new insights into the mechanisms and patterns of mitogenome rearrangements in Hydropsychidae.

Self-regulation mechanism difference of Chlorella vulgaris and Scenedesmus obliquus in toxic sludge extract caused by hydroquinone biodegradation.

Chlorella vulgaris (C. vulgaris) and Scenedesmus obliquus (S. obliquus) were compared to remove toxicity under conditions of sludge extract cultivation for 30 days. The toxicity of sludge extract, the growth characteristics, photosynthetic pigment, superoxide dismutase (SOD) enzyme and catalase (CAT) enzyme activities of the two microalgae were studied by contrast. The results showed that small molecular organic matter (<500 Da) was more easily utilized by microalgae. The toxicity in the toxic group of C. vulgaris and S. obliquus on the 30th day decreased to 56.8 ± 1.2% and 60.7 ± 2.8%, respectively. In the toxic group, the maximal SOD enzyme activity of C. vulgaris and S. obliquus were 2.02 U/mg proteins and 8.21 U/mg proteins, respectively, demonstrating that toxicity caused more oxidative damage to S. obliquus than to C. vulgaris. Proteomics analysis revealed that C. vulgaris mainly regulates energy synthesis and distribution primarily through sugar metabolism, and biomass synthesis primarily through carbon metabolism, whereas S. obliquus mainly regulates energy synthesis and distribution primarily through sugar metabolism and oxidative phosphorylation, resulting in sludge toxicity stress regulation.

Endogenous Hydrogen Sulfide Persulfidates Caspase-3 at Cysteine 163 to Inhibit Doxorubicin-Induced Cardiomyocyte Apoptosis.

Doxorubicin (DOX) is an efficient antitumor anthracycline drug, but its cardiotoxicity adversely affects the prognosis of the patients. In this study, we explored whether endogenous gasotransmitter hydrogen sulfide (H2S) could protect against DOX-induced cardiomyocyte apoptosis and its mechanisms. The results indicated that DOX significantly downregulated endogenous H2S production and endogenous synthetase cystathionine γ-lyase (CSE) expression and obviously stimulated the apoptosis in H9C2 cells. The supplement of H2S donor sodium hydrosulfide (NaHS) or overexpression of CSE inhibited DOX-induced H9C2 cell apoptosis. DOX enhanced the activities of caspase family members in cardiomyocytes, while NaHS attenuated DOX-enhanced caspase-3, caspase-2, and caspase-9 activities by 223.1%, 73.94%, and 52.29%, respectively. Therefore, taking caspase-3 as a main target, we demonstrated that NaHS or CSE overexpression alleviated the cleavage of caspase-3, suppressed caspase-3 activity, and inhibited the cleavage of poly ADP-ribose polymerase (PARP). Mechanistically, we found that H2S persulfidated caspase-3 in H9C2 cells and human recombinant caspase-3 protein, while the thiol-reducing agent dithiothreitol (DTT) abolished H2S-induced persulfidation of caspase-3 and thereby prevented the antiapoptotic effect of H2S on caspase-3 in H9C2 cells. The mutation of caspase-3 C148S and C170S failed to block caspase-3 persulfidation by H2S in H9C2 cells. However, caspase-3 C163S mutation successfully abolished the effect of H2S on caspase-3 persulfidation and the corresponding protection of H9C2 cells. Collectively, these findings indicate that endogenous H2S persulfidates caspase-3 at cysteine 163, inhibiting its activity and cardiomyocyte apoptosis. Sufficient endogenous H2S might be necessary for the protection against myocardial cell apoptosis induced by DOX. The results of the study might open new avenues with respect to the therapy of DOX-stimulated cardiomyopathy.

Polypyrrole Decorated Flower-like and Rod-like ZnO Composites with Improved Microwave Absorption Performance.

In this study, zinc oxide (ZnO)/polypyrrole (PPy) composites with flower- and rod-like structures were successfully fabricated by in situ polymerization and the hydrothermal method and used as microwave absorption (MWA) materials. The surface morphologies, crystal structures, and electromagnetic features of the as-prepared samples were measured by field-emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and vector network analyzer (VNA). The results show that the conductive polymer PPy was successfully decorated on the surface of ZnO substrates. The MWA ability of flower- and rod-like ZnO/PPy composites is significantly enhanced after introduction of PPy. Rod-like ZnO/PPy composites exhibited superior MWA properties than those of flower-like ZnO/PPy. The former achieved a minimum reflection loss (RLmin) of −59.7 dB at 15.8 GHz with a thickness of 2.7 mm, and the effective absorption bandwidth (EAB, RL < −10 dB) covered 6.4 GHz. PPy addition and stacked structure of rod-like ZnO/PPy composites can effectively improve the dielectric properties, form multiple reflections of incident electromagnetic waves, and generate an interfacial polarization effect, resulting in improved MWA properties of composite materials.

Endogenous SO2 Controls Cell Apoptosis: The State-of-the-Art.

SO2, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO2 acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO2 on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO2 can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO2 is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.

Adaptive Fixed-Time Control of Strict-Feedback High-Order Nonlinear Systems.

This paper examines the adaptive control of high-order nonlinear systems with strict-feedback form. An adaptive fixed-time control scheme is designed for nonlinear systems with unknown uncertainties. In the design process of a backstepping controller, the Lyapunov function, an effective controller, and adaptive law are constructed. Combined with the fixed-time Lyapunov stability criterion, it is proved that the proposed control scheme can ensure the stability of the error system in finite time, and the convergence time is independent of the initial condition. Finally, simulation results verify the effectiveness of the proposed control strategy.

Exposure to bisphenols and asthma morbidity among low-income urban children with asthma.

BACKGROUND: Bisphenol A (BPA) has been linked with pediatric asthma development and allergic airway inflammation in animal models. Whether exposure to BPA or its structural analogs bisphenol S (BPS) and bisphenol F (BPF) is associated with asthma morbidity remains unknown. OBJECTIVE: We examined associations between bisphenols and morbidity due to pediatric asthma. METHODS: We quantified concentrations of BPA, BPS, and BPF in 660 urine samples from 148 predominantly low-income, African American children (aged 5-17 years) with established asthma. We used biobanked biospecimens and data on symptoms, health care utilization, and pulmonary function and inflammation that were collected every 3 months over the course of a year. We used generalized estimating equations to examine associations between concentrations or detection of urinary bisphenols and morbidity outcomes and assessed heterogeneity of associations by sex. RESULTS: We observed consistent positive associations between BPA exposure and measures of asthma morbidity. For example, we observed increased odds of general symptom days (adjusted odds ratio [aOR] = 1.40 [95% C = 1.02-1.92]), maximal symptom days (aOR = 1.36 [95% CI = 1.00-1.83]), and emergency department visits (aOR = 2.12 [95% CI =1.28-3.51]) per 10-fold increase in BPA concentration. We also observed evidence of sexually dimorphic effects; BPA concentrations were associated with increased odds of symptom days and health care utilization only among boys. Findings regarding BPS and BPF did not consistently point to associations with asthma symptoms or health care utilization. CONCLUSION: We found evidence to suggest that BPA exposure in a predominantly low-income, minority pediatric cohort is associated with asthma morbidity and that associations may differ by sex. Our findings support additional studies, given the high pediatric asthma burden and widespread exposure to BPA in the United States.

Young children's exposure to phenols in the home: Associations between house dust, hand wipes, silicone wristbands, and urinary biomarkers.

BACKGROUND: Environmental phenols, such as parabens, bisphenol A, and triclosan, are ubiquitous in indoor environments because of their use in packaging, plastics, personal care products, and as anti-microbials. The primary pathways of exposure, as well as habits and behaviors that may lead to greater exposure, are still unclear. OBJECTIVES: Herein, we investigate the relationships between phenols found in residential environments by comparing levels in paired samples of house dust and hand wipes with children's urine. In addition, phenols were analyzed in a novel exposure tool, the silicone wristbands, to investigate which external matrix best correlates with individual exposure based on urinary phenol biomarkers. METHODS: Children aged 3-6 years in central North Carolina, United States, provided paired hand wipe (n = 202), wristband (n = 76), and spot urine samples (n = 180), while legal guardians completed questionnaires on habits and behaviors. House dust samples (n = 186) were collected from the main living area during home visits completed between 2014 and 2016. RESULTS: Environmental phenols were detected frequently in all matrices investigated. Ethyl, methyl, and propylparaben levels observed in hand wipes, dust, and on wristbands were significantly correlated to their associated urinary biomarkers. In addition, intra-paraben correlations were noted, with biomarkers of ethyl, methyl, and propylparabens generally positively and significantly correlated, which suggests co-application of parabens in products. Triclosan levels in dust were positive and significantly correlated with levels in hand wipes and wristbands and with urinary concentrations, suggesting non-personal care product sources may be important in children's overall triclosan exposure. Generally, chemicals on wristbands were more highly correlated with urinary biomarkers than with chemicals in hand wipes or house dust. In addition, more frequent lotion use was positively associated with urinary concentrations of paraben biomarkers. CONCLUSIONS: Our results suggest that the home environment is an important source of exposure which has been under-investigated for some environmental phenols (e.g., triclosan in house dust). Associations between wristbands and biomarkers of exposure, which were stronger than for hand wipes and house dust, suggest that silicone wristbands may provide a suitable exposure assessment tool for some phenols.

Mo2N-Ni/NF Heterostructure Boosts Electrocatalytic Hydrogen Evolution with Pt-Like Activity.

The sustainable development of a hydrogen economy requires hydrogen production from water electrolysis at a low cost, but the limited production of active and robust electrocatalysts using materials that are abundant on earth has restrained development. This article reports a heterostructure of a Mo2N phase and metal Ni nanocrystals and its activities in the hydrogen evolution reaction (HER) in alkaline electrolytes. Hydrogen is produced by the catalyst in alkaline electrolytes at a density of 10 mA cm-2 at an overpotential of only 20 mV with a small Tafel slope of 39.9 mV dec-1, in which the catalyst exhibits a synergetic effect of compact Mo2N and Ni interfacial connections, producing localized hotspots that accelerate water dissociation and hydrogen desorption. This makes the catalyst one of the most effective Pt-free species. Experimental and DFT theoretical results show that the exceptional HER electrocatalytic activity produced by the Mo2N-Ni/NF heterogeneous structure is related to the unique highly unshielded structure and high intrinsic activity accompanied by a nearly thermoneutral H-adsorption energy.

Correlates of exposure to phenols, parabens, and triclocarban in the Study of Environment, Lifestyle and Fibroids.

We performed a cross-sectional analysis to identify correlates of urinary concentrations of seven phenols (bisphenols A, F, and S; 2,4-dichlorophenol; 2,5-dichlorophenol; benzophenone-3; triclosan), triclocarban, and four parabens (butyl, ethyl, methyl, and propyl). We analyzed baseline data from 766 participants in the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study of 1693 Black women aged 23-34 years residing in Detroit, Michigan (2010-2012). We collected data on demographic, behavioral, and anthropometric factors via telephone interviews, clinic visits, and self-administered questionnaires. For each biomarker, we used linear regression models to estimate mean differences in log-transformed, creatinine-corrected concentrations across factors of interest. Each biomarker was detected in >50% of participants. Median creatinine-corrected concentrations were the highest for methyl paraben (116.8 µg/g creatinine), propyl paraben (16.8 µg/g creatinine), and benzophenone-3 (13.4 µg/g creatinine). Variables most strongly associated with biomarker concentrations included season of urine collection, education, and body mass index (BMI). BMI was positively associated with bisphenol A and S and triclocarban concentrations and inversely associated with butyl and methyl paraben concentrations. In this cohort of Black women, exposure to phenols, parabens, and triclocarban was prevalent and several factors were associated with biomarker concentrations.

Determinants and characterization of exposure to phthalates, DEHTP and DINCH among pregnant women in the PROTECT birth cohort in Puerto Rico.

BACKGROUND: As a result of evidence suggesting phthalate toxicity, their use has decreased in recent years. However, new phthalates and non-phthalate replacements have emerged in their place, with unknown potential impacts on health. METHODS: We measured 15 phthalate, two di(2-ethylhexyl)terephthalate (DEHTP), and two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) urinary metabolites, collected up to three times during pregnancy from 994 women in Northern Puerto Rico (2011-2017). We used tests of linear trend to assess changes in concentrations over time and linear mixed models to identify predictors of exposure (sociodemographic characteristics, drinking water sources, diet, product use). RESULTS: Several phthalate metabolites decreased over the study period indicating decreased exposure, while the geometric mean of DEHTP metabolites (molecular sum) increased threefold between 2014 and 2017. Intraclass correlations revealed low to moderate reproducibility of these biomarkers across pregnancy. Several metabolites were associated with maternal age, income, education, pre-pregnancy BMI, drinking public water, use of cleaning and personal care products, and ice cream consumption. DINCH metabolite concentrations remained low throughout the study period. CONCLUSION: Although exposure to some phthalates may be decreasing, exposure to replacements, such as DEHTP, is increasing. Additional studies are needed to further characterize sources of phthalate replacement chemicals and potential exposure-related health effects among vulnerable populations.

An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies.

BACKGROUND: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void. METHODS: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures. RESULTS: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%. CONCLUSIONS: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.