RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment.

Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer's disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aß1-42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aß1-42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.

Phthalate metabolites in breast milk from mothers in Southern China: Occurrence, temporal trends, daily intake, and risk assessment.

The extensive production and use of phthalates means that these compounds are now ubiquitous in the environment and various biota, which raises concerns about potential harmful health effects. In this study, phthalate metabolites (mPAEs) were measured in breast milk (n = 100) collected from mothers of southern China between 2014 - 2022. Of the nine target mPAEs, five were detected in all of the samples, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP). The total levels of mPAEs in breast milk ranged from 4.76 to 51.6 ng/mL, with MiBP and MnBP being the predominant isomers (MiBP + MnBP > 48.3%). Increasing trends were observed in MMP (5.7%/year) and MEHP (7.1%/year) levels during the study period, while a decreasing trend were observed in MiBP (-6.6%/year); no clear temporal trends were found for the other metabolites and total mPAE levels. The results indicate that exposure to phthalates is still prevalent in southern China. Breastfeeding was found to contribute to estimated daily phthalate intakes of 0.383-6.95 µg/kg-bw/day, suggesting insignificant health risks to infants based on dietary exposure. However, the increasing exposure to MMP and MEHP calls for more research into the possible sources and potential risks.

Isomer-specific analysis of nonylphenol and their transformation products in environment: A review.

Nonylphenols (NPs) are crucial fine chemicals widely employed in producing industrial and consumer surfactants that ultimately enter the environment through various pathways, leading to environmental pollution. NPs are suspected endocrine-disrupting chemicals that may accumulate in the body over time, resulting in unusual reproductive function. Due to limitations in analytical methods, NPs have typically been quantified as a whole in some studies. However, NPs are a mixture of multibranched structures, and different NP isomers exhibit distinct environmental behaviors and toxic effects. Therefore, it is critical to analyze environmental and human biological samples at the isomer-specific level to elucidate the contamination characteristics, human exposure load, and toxic effects of NPs. Accurately analyzing NP samples with various isomers, metabolites, and transformation products presents a significant challenge. This review summarizes recent advances in analytical research on NPs in technical products, environmental, and human biological samples, particularly emphasizing the synthesis and separation of standards and the transformation of NP homolog isomers in samples. Finally, the review highlights the research gaps and future research directions in this domain.

Distribution of phthalate metabolites, benzophenone-type ultraviolet filters, parabens, triclosan and triclocarban in paired human hair, nail and urine samples.

In this study, the distribution of nineteen ingredients of personal care product (PCPs), including seven metabolites of phthalates (mPAEs), five benzophenone-type ultraviolet filters (BPs), and seven antimicrobial agents (AAs), were investigated in paired human hair, nail and urine samples. The median concentrations of ΣmPAEs, ΣBPs and ΣAAs were 135, 2.76 and 179 ng/g in hair, 37.3, 2.95 and 297 ng/g in nails, and 345, 4.03 and 50.1 ng/mL in urine, respectively. Mono-methyl phthalate (49%), 2,4-dihydroxybenzophenone (45%) and triclosan (71%) were the most abundant mPAE, BP and AA in hair samples, respectively, and had similar abundance in nail samples. In contrast, mono-n-butyl phthalate (45%), 4-hydroxy benzophenone (29%) and methyl paraben (54%) were the predominant mPAE, BP and AA in urine samples, respectively. Significant differences in the concentrations of some target compounds were observed between male and female but inconsistent across different matrices. Moreover, most compounds with significant correlations had quite different correlation coefficients in each matrix. No significant correlations were found between hair, nail and urine samples for most of the target analytes. These results suggest these analytes have matrix-specific distribution, and it is necessary to use multiple matrices to comprehensively assess the risk of ingredients of PCPs to human health.

Internal exposure risk based on urinary metabolites of PAHs of occupation and non-occupation populations around a non-ferrous metal smelting plant.

The emission of various metals from non-ferrous metal smelting activities is well known. However, relative investigations on potential occupational exposure of organic pollutants are still limited. Herein, total of 619 human urine samples were collected from workers engaged in smelting activities and residents living near and/or far from the smelting sites, and ten mono-hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) in human urine were determined. The median levels of Σ10OH-PAHs in smelting workers (25.6 ng/mL) were significantly higher (p < 0.01) than that of surrounding residents (9.00 ng/mL) and rural residents as the control (8.17 ng/mL), indicating an increase in occupational PAH exposure in non-ferrous metal smelting activities. The composition profiles of OH-PAH congeners were similar in three groups, in which naphthalene metabolites accounted for 76-82% of the total. The effects of smoking, drinking, gender, BMI, and occupational categories on urinary OH-PAHs were considered. The partial correlation analysis showed an insignificant effect of non-ferrous metal smelting activities on PAH exposure for surrounding residents. In the health risk assessments, almost all smelting workers had cancer risks exceeded the acceptable level of 10-6. This study provides a reference to occupational PAH exposure and reinforce the necessary of health monitoring among smelting workers.

Polybrominated diphenyl ethers and bromophenols in paired serum, hair, and urine samples of e-waste dismantlers: Insights into hair as an indicator of endogenous exposure.

Polybrominated diphenyl ethers (PBDEs) are important pollutants during dismantling activities of electronic waste (e-waste) in China due to its large production and usage. Bromophenols (BPs), which are a kind of flame retardants and diphenyl ether bond cleavage metabolites of PBDEs, are often neglected in the assessment of human exposure to e-waste. Herein, 22 PBDEs and 19 BPs were determined in paired serum, hair, and urine samples collected from workers and residents of a typical e-waste dismantling site in southern China. Both PBDE and BP congeners were more frequently detected in hair than serum and urine samples. The medians of ΣPBDEs and ΣBPs were 350 and 547 ng/g dw in hair internal (hair-In) of occupational population, respectively, which were significantly higher than non-occupational population. However, a non-significant difference was found in levels of ΣPBDEs and ΣBPs in serum and urine between occupational and non-occupational populations, suggesting that hair analysis could easily differentiate between the exposure intensities of PBDEs and BPs to populations than serum and urine analyses. Moreover, levels of BPs in hair-In were 1-2 orders of magnitude higher than those in hair external (hair-Ex), while a non-significant difference was found in the levels of PBDEs. This result indicated that BPs might have originated from endogenous contribution. Notably, as the predominant congeners, the level of 2,4,6-tribromophenol (2,4,6-TBP) in hair-In was 3-8 times higher than that of BDE-209, while level of 2,4,6-TBP in hair-Ex was 1-3 times lower than that of BDE-209. Furthermore, in vivo experiments performed on Sprague-Dawley rats following a 28-day oral treatment with BDE-209 and 2,4,6-TBP verified that endogenous accumulation of 2,4,6-TBP in hair could be attributed to the metabolism of BDE-209 and exposure to 2,4,6-TBP. In conclusion, compared with PBDEs, biomonitoring phenolic compounds or metabolites with hair could better reflect human endogenous exposure.

Handwipes as indicators to assess organophosphate flame retardants exposure and thyroid hormone effects in e-waste dismantlers.

Dermal exposure is increasingly recognized as an important pathway for organic pollutant exposure. However, data on dermal exposure are limited, particularly with respect to the health effects. This study evaluated association between organophosphorus flame retardants (OPFRs) in handwipes and internal body burden on workers and adult residents in an electronic waste (e-waste) dismantling area. The impact of dermal exposure to OPFRs on thyroid hormones (THs) served as a biomarker for early effects. Triphenyl phosphate (TPhP) was the most detected compound in handwipes, with median levels of 1180, 200, and 24.0 ng in people identified as e-waste bakers, e-waste dismantlers, and adult residents. Among e-waste dismantlers, TPhP levels in handwipes were positively correlated with paired serum TPhP and urinary diphenyl phosphate (DPhP) levels. In multiple linear regression models controlling for sex, age and smoking, TPhP levels in handwipes of e-waste dismantlers were significantly negatively correlated with three THs used to evaluate thyroid function: serum reverse 3,3',5-triiodo-L-thyronine (rT3), 3,3'-diiodo-L-thyronine (3,3'-T2), and 3,5-diiodo-L-thyronine (3,5-T2). These findings suggest that handwipes can act as non-invasive exposure indicators to assess body burden of dermal exposure to TPhP and health effects on THs of e-waste dismantlers. This study highlights importance of OPFR effect on human THs through dermal exposure.

New Insights into Human Biotransformation of BDE-209: Unique Occurrence of Metabolites of Ortho-Substituted Hydroxylated Higher Brominated Diphenyl Ethers in the Serum of e-Waste Dismantlers.

Extremely high levels of decabromodiphenyl ether (BDE-209) are frequently found in the serum of occupationally exposed groups, such as e-waste dismantlers and firefighters. However, the metabolism of BDE-209 in the human body is not adequately studied. In this study, 24 serum samples were collected from workers at a typical e-waste recycling workshop in Taizhou, Eastern China, and the occurrence and fate of these higher brominated diphenyl ethers (PBDEs) were investigated. The median concentration of the total PBDEs in the serum was 199 ng/g lipid weight (lw), ranging from 125 to 622 ng/g lw. Higher brominated octa- to deca-BDEs accounted for more than 80% of the total PBDEs. Three ortho-hydroxylated metabolites of PBDEs─6-OH-BDE196, 6-OH-BDE199, and 6'-OH-BDE206─were widely detected with a total concentration (median) of 92.7 ng/g lw. The concentrations of the three OH-PBDEs were significantly higher than their octa- and nona-PBDE homologues, even exceeding those of the total PBDEs in several samples, indicating that the formation of OH-PBDEs was a major metabolic pathway of the higher brominated PBDEs in occupationally exposed workers. An almost linear correlation between 6-OH-BDE196 and 6-OH-BDE199 (R = 0.971, P < 0.001) indicates that they might undergo a similar biotransformation pathway in the human body or may be derived from the same precursor. In addition, the occurrence of a series of penta- to hepta- ortho-substituted OH-PBDEs was preliminarily identified according to their unique "predioxin" mass spectral profiles by GC-ECNI-MS. Taken together, the tentative metabolic pathway for BDE-209 in e-waste dismantlers was proposed. The oxidative metabolism of BDE-209 was mainly observed at the ortho positions to form 6'-OH-BDE-206, which later underwent a consecutive loss of bromine atoms at the meta or para positions to generate other ortho-OH-PBDEs. Further studies are urgently needed to identify the chemical structures of these ortho-OH-PBDE metabolites, and perhaps more importantly to clarify the potentially toxic effects, along with their underlying molecular mechanisms.

Atmospheric occurrences of nitrated and hydroxylated polycyclic aromatic hydrocarbons from typical e-waste dismantling sites.

Primitive electronic waste (e-waste) dismantling activities have been shown to be an important emissions source for a variety of toxic organic compounds, including carcinogenic polycyclic aromatic hydrocarbons (PAHs). Previous studies have found that some nitrated PAHs (NPAHs) are more toxic than their parent PAHs, however, little attention has been paid to the formation of PAH derivatives during e-waste processing and there is a lack of comprehensive data from field observations. In this study, the spatial distribution, temporal trends and atmospheric fate of NPAHs and hydroxylated PAHs (OH-PAHs) were investigated at typical e-waste dismantling sites, with monitoring data collected over three consecutive years. Compared to background levels, higher levels of NPAHs and OH-PAHs were found in air samples from an e-waste dismantling industrial park, with their seasonal and annual changes shown to be affected by e-waste dismantling activities. Atmospheric PM2.5 particles were found to have high relative abundances of NPAHs (76.9%-95.1%) and OH-PAHs (73.3%-91.6%), with particle-bound concentrations ranging from 20.1 to 88.8 and 37.1 to 107 pg m-3, respectively. The most abundant NPAH isomers were found to be 9-Nitroanthracene and 2-Nitrofluoranthene, while OH-PAH isomers containing 2-4 rings were predominant. Source identification was performed based on the specific diagnostic ratios of NPAH isomers, confirming that NPAH and OH-PAH emissions have multiple sources, including emissions related to the e-waste dismantling process, atmospheric photochemical reactions and traffic emissions. Further research on the fate of such derivatives and their potential use as markers for source identification, is urgently required.

Urinary metabolites and handwipe phthalate levels among adults and children in southern China: Implication for dermal exposure.

Paired handwipe and urine samples were collected from adult (n = 130) and child (n = 82) residents of a typical urban community in southern China to examine relationships between external and internal exposure as well as the contribution of dermal absorption to the exposure of phthalates. The concentrations and composition profiles of phthalates were similar in handwipes from both adults and children, and contained mainly di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP) and di-iso-butyl phthalate (DiBP), consistent with profiles of phthalates in air and dust. The major metabolites of these phthalates, i.e., mono-n-butyl phthalate (mnBP) from DnBP, mono-iso-butyl phthalate (miBP) from DiBP and three metabolites of DEHP (namely mEHP, mEHHP and mEOHP) were widely detected in paired urine samples. Positive correlations were found between contamination levels of DiBP and DnBP in handwipes and their corresponding urinary metabolites, whereas no significant correlation was observed for DEHP. This suggests that dermal absorption might be an important exposure pathway particularly for low molecular weight phthalates. Our study shows that dermal absorption is a non-negligible exposure pathway for phthalates, to which children are particularly sensitive since the contribution of dermal uptake to the internal exposure of phthalates was higher in children than adults.

Chiral signatures of polychlorinated biphenyls in serum from e-waste workers and their correlation with hydroxylated metabolites.

Elevated concentrations of polychlorinated biphenyls (PCBs) found in environmental media and biota from typical e-waste dismantling sites have raised concerns regarding their human body burden and potential negative health effects. In the present study, the enantiomeric compositions of three typical chiral congeners (PCB-95, PCB-132, and PCB-149) were measured in 24 serum samples from e-waste workers by using gas chromatography coupled to triple quadrupole tandem mass spectrometry. The mean enantiomer fractions (EFs) of chiral congeners in serum from the workers were 0.655 ± 0.103, 0.679 ± 0.164, and 0.548 ± 0.095 for PCB-95, PCB-132, and PCB-149, respectively. The (+) enantiomers of PCB-95, PCB-132, and PCB-149 were enantioselectively enriched in serum. Significant positive correlations were observed between the EF of the chiral congener PCB-95 and the total concentration of OH-PCBs, suggesting that EF values of chiral PCBs could be used to indicate the extent of biological metabolism. In addition, the EF of PCB-95 in serum samples increased with increasing work duration of the e-waste workers, thus demonstrating the usefulness of EF values of chiral PCBs as tracers of human exposure to PCBs. Because of the enantioselective enrichment of (+) enantiomers of PCB-95, PCB-132, and PCB-149, further studies are needed to explore the metabolism and toxicity of chiral contaminants in humans.

Liquid-liquid extraction combined with online cleanup for the simultaneous determination of PAHs by GC-MS/MS and their hydroxylated metabolites by LC-MS/MS in human fingernails.

A method was developed for the simultaneous determination of polycyclic aromatic hydrocarbons (PAHs) and their hydroxylated metabolites (OH-PAHs) in human fingernails using liquid-liquid extraction and online purification. After surface decontamination by rinsing with acetone, the fingernails were digested with sodium hydroxide and subjected to liquid-liquid extraction with a mixture of n-hexane and methyl tertbutyl ether. The organic extract was then fractionated using a silica-based solid-phase extraction (SPE) cartridge to obtain a PAH fraction eluted with n-hexane/dichloromethane (v/v, 95:5) and an OH-PAH fraction eluted with dichloromethane/ethyl acetate (v/v, 50:50). The PAH fraction was directly injected into an online gel permeation chromatography-gas chromatography-triple quadrupole tandem mass spectrometry (GPC-GC-MS/MS) system, enabling rapid determination of 16 PAHs. A parallel online SPE liquid chromatography tandem mass spectrometry (LC-MS/MS) method was used to determine 12 OH-PAHs. Validation experiments showed that the recovery of PAH and OH-PAH were within range of 67.4%-105.1% (RSD ≤ 10.1%) and 72.8%-102.3% (RSD ≤ 10.9%), respectively, with limits of quantitation (LOQ) of 0.06-0.8 ng/g and 0.15-3.1 ng/g, respectively. Forty-two human fingernail samples from residents of Southern China were analyzed to establish background PAH and OH-PAH levels in this region. Several PAHs and OH-PAHs were detected, at concentrations of 97.5 to 3,687 ng/g for PAHs and 24.2 to 767 ng/g for OH-PAHs. The dominant homologues were two- and three-ring PAH isomers, notably naphthalene (Nap), fluorene (Flu), and phenanthrene (Phe), as well as the corresponding hydroxylated metabolites 2-OH-Nap, OH-Flu, and OH-Phe. Smoking, consuming barbecued food, and age had no significant effects on PAH exposure, but a larger sample would be required to confirm this finding. The online purification strategy presented here expedites cleanup and purification during analysis of human fingernails and should facilitate non-invasive biomonitoring of PAHs in humans, particularly when analyzing large numbers of samples.

Occurrence and fate of polycyclic aromatic hydrocarbons from electronic waste dismantling activities: A critical review from environmental pollution to human health.

Electronic waste (e-waste) is one of the fastest-growing solid wastes and has become an urgent issue due to the potential adverse consequences of exposure to emitted toxic pollutants, especially for these occupational exposed workers and local residents. In this review, the environmental occurrences, emission characteristics, sources, and possible adverse effects of polycyclic aromatic hydrocarbons (PAHs) emitted from primitive e-waste dismantling activities are summarized. In general, the atmospheric levels of PAHs at typical e-waste sites, e.g., in Guiyu, China, have substantially decreased by more than an order of magnitude compared with levels a decade ago. The PAH concentrations in soil from old e-waste sites in China are also generally lower than those at newly emerged e-waste sites in India, Pakistan and Ghana. However, elevated concentrations of PAHs have been reported in human milk, hair and urine from the populations near these e-waste sites. Source apportionment both from bench-scale studies to field observations has demonstrated that the pyrolysis and combustion processing of electronic circuit board are mainly responsible for the emissions of various PAHs. In addition, some specific PAHs and their derivatives, such as triphenylbenzene, halogenated and oxygenated PAHs, have frequently been identified and could be considered as indicators in routine analysis in addition to the 16 U.S. EPA priority PAHs currently used.

Identifying Dermal Uptake as a Significant Pathway for Human Exposure to Typical Semivolatile Organic Compounds in an E-Waste Dismantling Site: The Relationship of Contaminant Levels in Handwipes and Urine Metabolites.

Dermal exposure to semivolatile organic compounds (SVOCs) has recently attracted widespread attention; understanding these exposures is particularly important for people whose skin is frequently exposed to different pollution surfaces. In this study, handwipes were collected from exposed occupational workers and local residents near a typical electronic waste (e-waste) dismantling area; urine samples were also sampled. The wipes were analyzed for three typical SVOCs: polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and organophosphate flame retardants (OPFRs). The median levels of PAHs, OPFRs, and PBDEs in handwipes from e-waste dismantlers were 96.0, 183, and 238 ng, respectively. The analytes were higher in the handwipes collected from workers than those from residents, indicating that they were subjected to greater dermal exposure during primitive e-waste dismantling activities. Among the three SVOCs, the strongest correlation was found between triphenyl phosphate (TPhP) in handwipes and diphenyl phosphate (DPhP) in paired urine; the next strongest correlations were between PAHs and PBDEs and their corresponding urinary metabolites. The results showed that TPhP contributed the highest exposure to e-waste dismantlers via dermal exposure. Our research highlights the importance of dermal exposure to TPhP, which should be considered in future exposure risk assessments.

Post-stroke Anxiety Analysis via Machine Learning Methods.

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.

PAHs and their hydroxylated metabolites in the human fingernails from e-waste dismantlers: Implications for human non-invasive biomonitoring and exposure.

Non-invasive human biomonitoring methods using hair and fingernails as matrices are widely used to assess the exposure of organic contaminants. In this work, a total of 72 human fingernails were collected from workers and near-by residents from a typical electronic waste (e-waste) dismantling site, and were analyzed for human exposure to polycyclic aromatic hydrocarbons (PAHs) and their mono-hydroxyl metabolites (OH-PAHs). The concentrations of PAHs and OH-PAHs were obtained as 7.97-551 and 39.5-3280 ng/g for e-waste workers (EW workers), 7.05-431 and 27.3-3320 ng/g for non-EW workers, 7.93-289 and 124-779 ng/g for adult residents, and 8.88-1280 and 181-293 ng/g for child residents, respectively. The composition profiles of PAHs in the human fingernails of the four groups were similar, with isomers of Phe, Pyr and Fluo being the predominated congeners, while 2-OH-Nap accounted for more than 70% of the total OH-PAHs. These contaminants were found most in the fingernails of EW workers, followed by non-EW workers, adult residents, and child residents, indicating e-waste dismantling activities are the major sources of PAH exposure. However, significantly higher levels of PAHs with 4-6 rings were observed only in workers as opposed to the residents, and a significant correlation between 3-OH-Flu (p < 0.05) and 2-OH-Phe (p < 0.01) in the fingernails and urine was observed, but no significant correlation was found between the concentration of OH-PAHs in matched hair and fingernail samples. In addition, the levels of PAHs in fingernails increased with the age of EW workers. This is the first study to explore the accumulation and distribution of PAHs and OH-PAHs in human fingernails, which would provide valuable insight into non-invasive biomonitoring and health risk assessment of PAHs.

Occurrence and distribution of typical semi-volatile organic chemicals (SVOCs) in paired indoor and outdoor atmospheric fine particle samples from cities in southern China.

Interest in the potential human health of semi-volatile organic chemicals (SVOCs) in indoor and outdoor environments has made the exposure assessment and source appointment a priority. In this study, paired indoor and outdoor atmospheric fine particle (PM2.5) samples were collected from 15 homes representing five typical urban cities in southern China. Four typical SVOCs, including 16 congeners of polycyclic aromatic hydrocarbons (PAHs), 13 congeners of organophosphorus flame retardants (OPFRs) and 8 congeners of polybrominated diphenyl ethers (PBDEs), as well as tetrabromobisphenol A (TBBPA) and its three debrominated congeners were analyzed. The highest total concentrations were found for OPFRs, followed by PAHs, PBDEs, and TBBPA. The indoor concentrations of two alkyl-OPFR isomers, tributylphosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP), were 4.3 and 11 times higher, respectively, than those of outdoors (p < 0.05). Additionally, the ratios of indoor to outdoor concentrations of alkyl-OPFR isomers varied greatly, suggesting that these compounds originated mainly from different household goods and products used in individual homes. The outdoor concentrations of PAHs and highly brominated PBDEs (BDE-209) typically exceeded the indoor concentrations. Significant correlations were also found between indoor and outdoor PM2.5 samples for PAHs and BDE-209, indicating that outdoor sources such as vehicle exhausts and industrial activities strongly influence their atmospheric occurrence. Additionally, the concentrations of debrominated TBBPA derivatives were higher than those of TBBPA in over 33% of both indoor and outdoor air particle samples. Nevertheless, our results indicated that inhalation exposure to typical SVOCs posed no non-carcinogenic risks to the human body. Although we observed notable differences in the sources, occurrences, and distributions of typical SVOC congeners, more studies using matched samples are still needed to unambiguously identify important indoor and outdoor sources in order to accurately assess the contributions of different sources and the associated human exposure risks.

New Mixed Bromine/Chlorine Transformation Products of Tetrabromobisphenol A: Synthesis and Identification in Dust Samples from an E-Waste Dismantling Site.

The large-scale production and usage of tetrabromobisphenol A (TBBPA) and its analogues have caused widespread contamination, raising concern about their potential endocrine disruption effects on both humans and ecosystems. In the present study, debromination and unknown mixed bromine/chlorine transformation products of TBBPA (X-BBPA) were screened in dust samples from an e-waste dismantling site. Five monochloro products (2-chloro-2',6,6'-TriBBPA, 2-chloro-2',6-DiBBPA, 2-chloro-2',6'-DiBBPA, 2-chloro-2'-MoBBPA, and 2-chloro-6-MoBBPA) and two dichloro products (2,2'-dichloro-6,6'-DiBBPA and 2,2'-dichloro-6-MoBBPA) were successfully synthesized and structurally identified. TBBPA and its transformation products were detected by comparison of their mass spectra and retention times with those of synthetic standards. The mean concentration of X-BBPA was 1.63 × 104 ng/g in e-waste dismantling workshop dust samples based on dry weight, which was at a similar level to TBBPA. However, it was 1 order of magnitude lower than the concentrations of the debromination congeners. Thus, both debromination and chlorine-bromine exchange may be important reactions during the thermal processing of e-waste. The results on mixed chlorinated/brominated TBBPA transformation products provided new insights into TBBPA transformation. The elevated levels of the transformation products of TBBPA suggested that these products should be targeted to avoid underestimation of possible health risks.

Bilateral middle cerebellar peduncle lesions: Neuroimaging features and differential diagnoses.

OBJECTIVES: Lesions limited to the bilateral middle cerebellar peduncles (MCPs) are uncommon. This retrospective study investigated diseases with a proclivity for the bilateral MCPs and explored the associations between their neuroimaging features and clinical findings for the differential diagnosis of such lesions. METHODS: We enrolled 26 patients who were admitted to our department between January 2016 and March 2019 with bilateral MCP abnormalities on magnetic resonance imaging (MRI). The demographic, clinical, and neuroimaging characteristics, and the biomarkers and diagnoses were evaluated. RESULTS: Although all patients exhibited symmetrical bilateral MCP hypointensities on T1-weighted imaging and hyperintensities on T2-weighted and fluid-attenuated inversion recovery imaging, they were diagnosed with different conditions. Diagnoses included acute cerebral infarction (ACI) (n = 9, 34.62%), Wallerian degeneration (WD) (n = 8, 30.77%), multiple system atrophy (MSA) (n = 6, 23.08%), neuromyelitis optica (NMO) (n = 1, 3.85%), heroin-induced leukoencephalopathy (n = 1, 3.85%), and primary central nervous system lymphoma (PCNSL) (n = 1, 3.85%). Patients with ACI exhibited bilateral MCP-restricted diffusion hyperintensities on diffusion-weighted imaging and corresponding stenosis or occlusion of the vertebrobasilar system. The initial MRI of patients with WD depicted pontine infarctions, while symmetrical MCP lesions were observed on follow-up MRI. Symmetrical MCP lesions, cruciform hyperintensity, and marked atrophy in the posterior fossa were characteristic manifestations of MSA. Longitudinally extensive myelitis affecting more than three vertebral segments on cervical MRI and positive serum AQP4-IgG may be indicative of NMO. Heroin-induced leukoencephalopathy was characterized by extra-symmetrical lesions in the posterior limbs of the internal capsules, while the anterior limbs were spared. PCNSL was indicated by a significant and characteristic "fist" sign on contrast-enhanced MRI. CONCLUSIONS: Bilateral MCP lesions were most frequently observed in cerebrovascular diseases, followed by neurodegenerative diseases, inflammatory diseases, toxic encephalopathies, and lymphomas. Our findings demonstrate that bilateral MCP signal abnormalities are more common in patients with ACI and WD, with fewer degenerative processes than previously believed. The high frequency of WD may be attributed to the specific awareness of this pathology. WD can also present with stage-related restricted diffusion and should not be mistaken for a new infarction. The symmetrical bilateral MCP hypointensities on T1-weighted imaging and hyperintensities on T2-weighted imaging often raise concern regarding a demyelinating process. Our findings emphasize that neurologists should consider the aforementioned conditions and correlate the specific neuroimaging characteristics and medical history before arriving at the final diagnosis.

Derivatization gas chromatography negative chemical ionization mass spectrometry for the analysis of trace organic pollutants and their metabolites in human biological samples.

Gas chromatography negative chemical ionization mass spectrometry (GC-NCI-MS) is a preferred instrumental approach for the trace and ultra-trace analysis of various toxic organics and their metabolites in human biological fluids. Specifically, the method has played an important role in the highly sensitive and specific quantitative detection of persistent highly halogenated compounds in environmental matrices and biota during the past few decades. However, for the analysis of toxic metabolites with active hydrogen atoms, such as acids, alcohols, and phenolic compounds, from biological matrixes or organics without electronegative atoms or groups, a derivatization step is often needed prior to GC analysis. Such derivatization aims to change the properties of targets to improve their separation, increase their volatility, and enhance the sensitivity of instrumental detection. This review summarizes three derivatization strategies commonly used for GC methods, i.e., alkylation, silylation, and acylation, together with their application combined with GC-NCI-MS for the high sensitivity analysis of toxic organic metabolites in the human body. The advantages and disadvantages of each derivatization method and potential directions for future applications are discussed. Given the broad variety of applications as well as the compound-specific sensitivity for the ultra-trace analysis of target xenobiotics in human biological fluids, subsequent studies are required to develop convenient, faster derivatization procedures and reagents better suited for routine analysis. Graphical abstract.