Programmable Lanthanide Metal-Organic Framework for Ultra-Efficient Nucleic Acids Extraction and Interaction Analysis.

Efficient, mild, and reversible adsorption of nucleic acids onto nanomaterials represents a promising analytical approach for medical diagnosis. However, there is a scarcity of efficient and reversible nucleic acid adsorption nanomaterials. Additionally, the lack of comprehension of the molecular mechanisms governing their interactions poses significant challenges. These issues hinder the rational design and analytical applications of the nanomaterials. Herein, we propose an ultra-efficient nucleic acid affinity nanomaterial based on programmable lanthanide metal-organic frameworks (Ln-MOFs). Through experiments and density functional theory calculations, a rational design guideline for nucleic acid affinity of Ln-MOF was proposed, and a modular and flexible preparation scheme was provided. Then, Er-TPA (terephthalic acid) MOF emerged as the optimal candidate due to its pore size-independent adsorption and desorption capabilities for nucleic acids, enabling ultra-efficient adsorption (about 150% mass ratio) within 1 min. Furthermore, we elucidate the molecular-level mechanisms underlying the Ln-MOF adsorption of single- and double-stranded DNA and G4 structures. The affinity nanomaterial based on Ln-MOF exhibits robust nucleic acid extraction capability (4-fold higher than commercial reagent kits) and enables mild and reversible CRISPR/Cas9 functional regulation. This method holds significant promise for broad application in DNA/RNA liquid biopsy and gene editing, facilitating breakthroughs in analytical chemistry, pharmacy, and medical research.

Dispersive solid-phase extraction based on zirconium metal-organic framework coupled with gas chromatography-mass spectrometry for determining sugar phosphates in biological samples.

BACKGROUND: Sugar phosphates (SPx) play important role in the metabolism of the organism. SPx such as glycerate 3-phosphate, fructose 6-phosphate and glucose 6-phosphate in biological samples have the poor stability, similar structure and low abundance, which make their separation and detection more challenging. METHOD: UiO-66-NH2 and ZrO2 coated SiO2(SBA-15) hard-core-shell adsorbents (UiO-66-NH2@SBA-15 and ZrO2@SBA-15) were synthesized, which were further used for dispersive solid-phase extraction for enriching the SPx in biological samples. The protocol was developed by UiO-66-NH2@SBA-15 and ZrO2@SBA-15 coupled with gas chromatography-mass spectrometry for the detection of trace SPx. The univariate experiment and response surface methodology were used to optimize the adsorption and desorption conditions. RESULTS: The adsorbents showed excellent adsorption capacity and specificity towards SPx, which were proved by adsorption and selective experiments. Under the optimized conditions, there were good linearity within the range of 5.0-5000.0 ng mL-1, low limits of detection (0.001-1.0 ng mL-1), low limits of quantification (0.005-5.0 ng mL-1) and good precision (relative standard deviation less than 14.7 % for intra-day and inter-day). The satisfactory recoveries (89.1-113.8 %) and precision (0.5-14.6 %) were obtained when the sorbents were used to extract SPx from serum, saliva and cell samples. Moreover, UiO-66-NH2@SBA-15 was applied to the quantitative analysis of SPx from gastric cancer patients, because of a higher adsorption capacity (169.5-196.1 mg g-1). CONCLUSIONS: UiO-66-NH2@SBA-15 showed great potential in the extraction of SPx in biological samples, which was beneficial to find out the metabolic change of SPx and explain the pathogenesis of the disease.

Mitigation of benzyl butyl phthalate toxicity in male germ cells with combined treatment of parthenolide, N-acetylcysteine, and 3-methyladenine.

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 µM. Exposure to 50 µM BBP, approximating the IC50 of 53.9 µM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 µM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity.

Assessment of neuro-pulmonary crosstalk in asthmatic mice: effects of DiNP exposure on cellular respiration, mitochondrial oxidative status and apoptotic signaling.

Human health is becoming concerned about exposure to endocrine disrupting chemicals (EDCs) emanating from plastic, such as phthalates, which are industrially employed as plasticizers in the manufacturing of plastic products. Due to some toxicity concerns, di(2-ethylhexyl) phthalate (DEHP) was replaced by diisononyl phthalate (DiNP). Recent data, however, highlights the potential of DiNP to interfere with the endocrine system and influence allergic responses. Asthma affects brain function through hypoxia, systemic inflammation, oxidative stress, and sleep disturbances and its effective management is crucial for maintaining respiratory and brain health. Therefore, in DiNP-induced asthmatic mice, this study investigated possible crosstalk between the lungs and the brain inducing perturbations in neural mitochondrial antioxidant status, inflammation biomarkers, energy metabolizing enzymes, and apoptotic indicators. To achieve this, twelve (n = 12, 20-30 g) male BALB/c mice were divided into two (2) experimental groups, each with five (6) mice. Mice in group II were subjected to 50 mg/kg body weight (BW) DiNP (Intraperitoneal and intranasal), while group I served as the control group for 24 days. The effects of DiNP on neural energy metabolizing enzymes (Hexokinase, Aldolase, NADase, Lactate dehydrogenase, Complex I, II, II & IV), biomarkers of inflammation (Nitric oxide, Myeloperoxidase), oxidative stress (malondialdehyde), antioxidants (catalase, glutathione-S-transferase, and reduced glutathione), oncogenic and apoptotic factors (p53, K-ras, Bcl, etc.), and brain histopathology were investigated. DiNP-induced asthmatic mice have significantly (p < 0.05) altered neural energy metabolizing capacities due to disruption of activities of enzymes of glycolytic and oxidative phosphorylation. Other responses include significant inflammation, oxidative distress, decreased antioxidant status, altered oncogenic-apoptotic factors level and neural degeneration (as shown in hematoxylin and eosin-stained brain sections) relative to control. Current findings suggest that neural histoarchitecture, energy metabolizing potentials, inflammation, oncogenic and apoptotic factors, and mitochondrial antioxidant status may be impaired and altered in DiNP-induced asthmatic mice suggesting a pivotal crosstalk between the two intricate organs (lungs and brain).

BMSC loaded photo-crosslinked hyaluronic acid/collagen hydrogel incorporating FG4592 for enhanced cell proliferation and nucleus pulposus differentiation.

Intervertebral disc degeneration arises from damage or degeneration of the nucleus pulposus (NP). In this study, we developed a photo-crosslinkable hydrogel incorporating FG4592 to support the growth and differentiation of bone-marrow-derived mesenchymal stem cells (BMSC). Initially, hyaluronic acid was modified with tyramine and combined with collagen to introduce riboflavin as a photo-crosslinker. This hydrogel transitioned from liquid to gel upon exposure to blue light in 3 min. The results showed that the hydrogel was biodegradable and had mechanical properties comparable to those of human NP tissues. Scanning electron microscopy after BMSC seeding in the hydrogel revealed an even distribution, and cells adhered to the collagen fibers in the hydrogel with minimal cell mortality. The effect of FG4592 on BMSC proliferation and differentiation was examined, revealing the capability of FG4592 to promote BMSC proliferation and direct differentiation resembling human NP cells. After cultivating BMSCs in the photo-crosslinked hydrogel, there was an upregulation in the expression of glycosaminoglycans, aggrecan, type II collagen, and keratin 19 proteins. Cross-species analyses of rat and human BMSCs revealed consistent results. For potential clinical applications, BMSC loaded with photo-crosslinked hydrogels can be injected into damaged intervertebral disc to facilitate NP regeneration.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Arbuscular mycorrhizal fungi by inducing watermelon roots secretion phthalates, altering soil enzyme activity and bacterial community composition to alleviate the watermelon wilt.

BACKGROUND: Long-term continuous cropping has resulted in the frequent occurrence of fusarium wilt of watermelon (Citrullus lanatus). AMF inoculation can alleviate the continuous cropping barrier and reduce the incidence of fusarium wilt of watermelon. Our previous study found that the root exudates of mycorrhizal watermelon can enhance watermelon resistance to this disorder. It is necessary to further isolate and identify the specific compounds in root exudates of mycorrhizal watermelon and explore their control effects on fusarium wilt of continuous cropping watermelon. RESULT: The results of this study showed that the root system of watermelon seedlings inoculated with AMF (Funneliformis mosseae or Glomus versiforme) secreted diisooctyl phthalate (A) and dibutyl phthalate (B). Compared with water treatment, treatment with 0.1 ml/L (A1, B1), 0.5 ml/L (A2, B2) and 1 ml/L (A3, B3) of A or B significantly increased soil enzyme activities, the numbers of bacteria and actinomycetes, and the bacteria/fungi ratio in the rhizosphere. Furthermore, the Disease indexes (DI) of A1 and B3 were 25% and 20%, respectively, while the prevention and control effects (PCE) were 68.8% and 75%, respectively. In addition, diisooctyl phthalate or dibutyl phthalate increased the proportions of Gemmatimonadetes, Chloroflexi, and Acidobacteria in the rhizosphere of continuous cropping watermelon, and decreased the proportions of Proteobacteria and Firmicutes, with Novosphingobium, Kaistobacter, Bacillus, and Acinetobacter as the predominant bacteria. Compared with the water treatment, the abundance of Neosphingosaceae, Kateybacterium and Bacillus in the A1 group was increased by 7.33, 2.14 and 2.18 times, respectively, while that in the B2 group was increased by 60.05%, 80.24% and 1 time, respectively. In addition, exogenous diisooctyl phthalate and dibutyl phthalate were shown to promote growth parameters (vine length, stem diameter, fresh weight and dry weight) and antioxidant enzyme system activities (SOD, POD and CAT) of continuous cropping watermelon. CONCLUSION: Lower watermelon fusarium wilt incidence in mycorrhizal watermelons was associated with phthalate secretion in watermelons after AMF inoculation. Exogenous diisooctyl phthalate and dibutyl phthalate could alleviate the continuous cropping disorder of watermelon, reduce the incidence of fusarium wilt, and promote the growth of watermelon by increasing the enzyme activities and the proportion of beneficial bacteria in rhizosphere soil. In addition, the low concentration of phthalate diisooctyl and high concentration of phthalic acid dibutyl works best. Therefore, a certain concentration of phthalates in the soil can help alleviate continuous cropping obstacles.

Environmental monobutyl phthalate exposure promotes liver cancer via reprogrammed cholesterol metabolism and activation of the IRE1α-XBP1s pathway.

Humans are widely exposed to phthalates, a major chemical plasticizer that accumulates in the liver. However, little is known about the impact of chronic phthalate exposure on liver cancer development. In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. Interestingly, we found that long-term MBP exposure significantly accelerated the growth of HepG2 cells in vitro and in vivo, but barely altered the function of L02 cells. MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, where cholesterol accumulation subsequently activated the IRE1α-XBP1s axis of the unfolded protein response. As a result, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells. In addition, we also showed that MBP-induced cholesterol accumulation fostered an immunosuppressive microenvironment by promoting tumor-associated macrophage polarization toward the M2 type. Together, these results suggest that environmental phthalates exposure may facilitate liver cancer progression, and alerts phthalates exposure to patients who already harbor liver tumors.

Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

Cu-BTC Derived Mesoporous CuS Nanomaterial as Nanozyme for Colorimetric Detection of Glutathione.

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 µM and 20-300 µM with a detection limit of 0.1 µM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.

Electrochemical Nanosensor for the Simultaneous Determination of Anticancer Drugs Epirubicin and Topotecan Using UiO-66-NH2/GO Nanocomposite Modified Electrode.

In this work, UiO-66-NH2/GO nanocomposite was prepared using a simple solvothermal technique, and its structure and morphology were characterized using field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). An enhanced electrochemical sensor for the detection of epirubicin (EP) was proposed, which utilized a UiO-66-NH2/GO nanocomposite-modified screen-printed graphite electrode (UiO-66-NH2/GO/SPGE). The prepared UiO-66-NH2/GO nanocomposite improved the electrochemical performance of the SPGE towards the redox reaction of EP. Under optimized experimental conditions, this sensor demonstrates a remarkable limit of detection (LOD) of 0.003 µM and a linear dynamic range from 0.008 to 200.0 µM, providing a highly capable platform for sensing EP. Furthermore, the simultaneous electro-catalytic oxidation of EP and topotecan (TP) was investigated at the UiO-66-NH2/GO/SPGE surface utilizing differential pulse voltammetry (DPV). DPV measurements revealed the presence of two distinct oxidation peaks of EP and TP, with a peak potential separation of 200 mV. Finally, the UiO-66-NH2/GO/SPGE sensor was successfully utilized for the quantitative analysis of EP and TP in pharmaceutical injection, yielding highly satisfactory results.

Dual-ligand Eu-MOF/CuS@Au Heterostructure Array-based ECL Sensor for MiRNA-128 Detection in Glioblastoma Tissues.

In this work, the dual-ligand lanthanide metal-organic framework (MOF)-based electrochemiluminescence (ECL) sensor was constructed for the detection of miRNA-128 in glioblastoma (GBM) diagnosis. The luminescent Eu-MOF (EuBBN) was synthesized with terephthalic acid (BDC) and 2-amino terephthalic acid (BDC-NH2) as dual-ligand. Due to the antenna effect, EuBBN with conjugated-π structure exhibited strong luminescent signal and high quantum efficiency, which can be employed as ECL nanoprobe. Furthermore, the novel plasmonic CuS@Au heterostructure array has been prepared. The localized surface plasmon resonance coupling effect of the CuS@Au heterostructure array can amplify the ECL signal of EuBBN significantly. The EuBBN/CuS@Au heterostructure array-based sensing system has been prepared for the detection of miRNA-128 with a wide linear range from 1 fM to 1 nM and a detection limit of 0.24 fM. Finally, miRNA-128 in the clinic GBM tissue sample has been analysis for the distinguish of tumor grade successfully. The results demonstrated that the dual-ligand MOF/CuS@Au heterostructure array-based ECL sensor can provide important support for the development of GBM diagnosis.

Associations of phthalates with accelerated aging and the mitigating role of physical activity.

Phthalates are positioned as potential risk factors for health-related diseases. However, the effects of exposure to phthalates on accelerated aging and the potential modifications of physical activity remain unclear. A total of 2317 participants containing complete study-related information from the National Health and Nutrition Examination Survey 2007-2010 were included in the current study. We used two indicators, the Klemera-Doubal method biological age acceleration (BioAgeAccel) and phenotypic age acceleration (PhenoAgeAccel), to assess the accelerated aging status of the subjects. Multiple linear regression (single pollutant models), weighted quantile sum (WQS) regression, Quantile g-computation, and Bayesian kernel machine regression (BKMR) models were utilized to explore the associations between urinary phthalate metabolites and accelerated aging. Three groups of physical activity with different intensities were used to evaluate the modifying effects on the above associations. Results indicated that most phthalate metabolites were significantly associated with BioAgeAccel and PhenoAgeAccel, with effect values (ß) ranging from 0.16 to 0.21 and 0.16-0.37, respectively. The WQS indices were positively associated with BioAgeAccel (0.33, 95% CI: 0.11, 0.54) and PhenoAgeAccel (0.50, 95% CI: 0.19, 0.82). Quantile g-computation indicated that phthalate mixtures were associated with accelerated aging, with effect values of 0.15 (95% CI: 0.02, 0.28) for BioAgeAccel and 0.39 (95% CI: 0.12, 0.67) for PhenoAgeAccel respectively. The BKMR models indicated a significant positive association between the concentrations of urinary phthalate mixtures with the two indicators. In addition, we found that most phthalate metabolites showed the strongest effects on accelerated aging in the no physical activity group and that the effects decreased gradually with increasing levels of physical activity (P < 0.05 for trend). Similar results were also observed in the mixed exposure models (WQS and Quantile g-computation). This study indicates that phthalates exposure is associated with accelerated aging, while physical activity may be a crucial barrier against phthalates exposure-related aging.

Insights into pollution characteristics and human health risks of plasticizer phthalate esters in shellfish species.

The ubiquitous application of phthalate esters (PAEs) as plasticizers contributes to high levels of marine pollution, yet the contamination patterns of PAEs in various shellfish species remain unknown. The objective of this research is to provide the first information on the pollution characteristics of 16 PAEs in different shellfish species from the Pearl River Delta (PRD), South China, and associated health risks. Among the 16 analyzed PAEs, 13 were identified in the shellfish, with total PAE concentrations ranging from 23.07 to 3794.08 ng/g dw (mean = 514.35 ng/g dw). The PAE pollution levels in the five shellfish species were as follows: Ostreidae (mean = 1064.12 ng/g dw) > Mytilus edulis (mean = 509.88 ng/g dw) > Babylonia areolate (mean = 458.14 ng/g dw) > Mactra chinensis (mean = 378.90 ng/g dw) > Haliotis diversicolor (mean = 335.28 ng/g dw). Dimethyl phthalate (DMP, mean = 69.85 ng/g dw), diisobutyl phthalate (DIBP, mean = 41.39 ng/g dw), dibutyl phthalate (DBP, mean = 130.91 ng/g dw), and di(2-ethylhexyl) phthalate (DEHP, mean = 226.23 ng/g dw) were the most abundant congeners. Notably, DEHP constituted the most predominant fraction (43.98 %) of the 13 PAEs detected in all shellfish from the PRD. Principal component analysis indicated that industrial and domestic emissions served as main sources for the PAE pollution in shellfish from the PRD. It was estimated that the daily intake of PAEs via shellfish consumption among adults and children ranged from 0.004 to 1.27 µg/kgbw/day, without obvious non-cancer risks (< 0.034), but the cancer risks raised some alarm (2.0 × 10-9-1.4 × 10-5). These findings highlight the necessity of focusing on marine environmental pollutants and emphasize the importance of ongoing monitoring of PAE contamination in seafood.

Exploring the relationships between exposure levels of bisphenols and phthalates and prostate cancer occurrence.

We established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously analyzing the metabolites of bisphenols and phthalates in urine to identify the associations between these exposure levels and prostate cancer (PCa) based on a case-control study. After purifying urine samples with SPE, 18 metabolites were separated on a C18 column, and MS detection was performed. The UPLC-MS/MS method has been proven effective at evaluating bisphenol and phthalate exposure (0.020-0.20 µg/L of the limits of detection, 71.8 %∼119.4 % of recoveries, 0.4 %∼8.2 % of precision). Logistic regression explored the association between exposure level and PCa in 187 PCa cases and 151 controls. The detection rates of bisphenol A (BPA) and most phthalate metabolites were 100 % ranging from 0.06-46.74 and 0.12-899.92 µg/g creatinine, respectively, while the detection rates of other bisphenols and mono-benzyl phthalate (MBzP) are low, ranging from 0 % to 21.85 %. Correlation analysis of the metabolite levels indicated that the exposure sources of BPA, di-ethyl phthalate (DEP), and di(2-ethylhexyl) phthalate (DEHP) were different, and that the exposure sources of di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP) may differ between two groups. Logistic regression analysis revealed that BPA (OR<0.45 vs ≥1.43 =10.02) and DEHP exposure (OR<21.75 vs ≥45.42 =48.26) increased the risk of PCa.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women.

BACKGROUND: Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). OBJECTIVE: We estimated associations between hair product use and EDC biomarker concentrations. METHODS: We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23-34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. RESULTS: Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. CONCLUSION: Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women.

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction.

BACKGROUND: Phthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. METHODS: Participants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005-2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. RESULTS: Metabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. CONCLUSION: Our study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

Occurrence and combined exposure of phthalate esters in urban soil, surface dust, atmospheric dustfall, and commercial food in the semi-arid industrial city of Lanzhou, Northwest China.

A total of 138 samples including urban soil, surface dust, atmospheric dustfall, and commercial food were collected from the semi-arid industrial city of Lanzhou in Northwest China, and 22 phthalate esters (PAEs) were analyzed in these samples by gas chromatography-mass spectrometry for the pollution characteristics, potential sources, and combined exposure risks of PAEs. The results showed that the total concentration of 22 PAEs (Æ©22PAEs) presented surface dust (4.94 × 104 ng/g) â‰« dustfall (1.56 × 104 ng/g) â‰« food (2.14 × 103 ng/g) â‰« urban soil (533 ng/g). Di-n-butyl phthalate (DNBP), di-isobutyl phthalate, di(2-ethylhexyl) phthalate (DEHP), and di-isononyl phthalate/di-isodecyl phthalate were predominant in the environmental media and commercial food, being controlled by priority (52.1%-65.5%) and non-priority (62.1%) PAEs, respectively. Elevated Æ©22PAEs in the urban soil and surface dust was found in the west, middle, and east of Lanzhou. Principal component analysis indicated that PAEs the urban soil and surface dust were related with the emissions of products containing PAEs, atmosphere depositions, and traffic and industrial emissions. PAEs in the foods were associated with the growth and processing environment. The health risk assessment of United States Environmental Protection Agency based on the Chinese population exposure parameters indicated that the total exposure dose of 22 PAEs was from 0.111 to 0.226 mg/kg/day, which were above the reference dose (0.02 mg/kg/day) and tolerable daily intake (TDI, 0.05 mg/kg/day) for DEHP (0.0333-0.0631 mg/kg/day), and TDI (0.01 mg/kg/day) for DNBP (0.0213-0.0405 mg/kg/day), implying that the exposure of PAEs via multi-media should not be ignored; the total non-carcinogenic risk of six priority PAEs was below 1 for the three environmental media (1.21 × 10-5-2.90 × 10-3), while close to 1 for food (4.74 × 10-1-8.76 × 10-1), suggesting a potential non-carcinogenic risk of human exposure to PAEs in food; the total carcinogenic risk of BBP and DEHP was below 1 × 10-6 for the three environmental media (9.13 × 10-10-5.72 × 10-7), while above 1 × 10-4 for DEHP in food (1.02 × 10-4), suggesting a significantly carcinogenic risk of human exposure to DEHP in food. The current research results can provide certain supports for pollution and risk prevention of PAEs.

Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

Customizable Zr-MOF nanoantidote-based multieffective arsenic detoxification and its extended low-toxic therapy.

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.