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Some studies have shown that famine exposure during adolescence can increase cardiovascular disease and diabetes susceptibility in later life. The association between famine exposure in adolescence and overweight/obesity and abdominal obesity in adulthood has been inconsistent. Based on previous studies, we hypothesized that famine exposure in adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. Eight databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched from their inception until November 2021. We initially identified 3982 records and finally included 7 articles after screening. The included articles were of moderate to high quality, containing 16 estimates of overweight/obesity and 3 estimates of abdominal obesity. Pooled odds ratios (ORs) with 95% CIs were used to estimate the association between them. The random effects model was adopted as the pooling method. There was a significant association between famine exposure in adolescence and overweight/obesity in adulthood (OR, 1.17; 95% CI, 1.02-1.33). Adolescents exposed to famine had a greater risk of abdominal obesity in adulthood than their unexposed counterparts (OR, 1.35; 95% CI, 1.03-1.76). These results were more pronounced in females than in males. In summary, our meta-analysis indicates that famine exposure during adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. This suggests that we need to pay timely attention to the nutritional status of adolescents to prevent adverse health consequences of malnutrition. More high-quality studies are needed to confirm these conclusions, given the limitations of this study.

Background Some evidence shows that aspirin can reduce the morbidity and mortality of different cancers, including breast cancer. Aspirin has become a new focus of cancer prevention and treatment research at present, however, clinical studies found conflicting conclusions of its anticancer characteristics. Materials and Methods A systematic literature search was performed in 8 electronic databases. The pooled relative risk (RR) with 95% confidence interval (CI) was calculated using the random effects model to estimate the effect of aspirin on breast cancer. Results Forty-two published articles with 99,769 patients were identified. The meta-analysis showed a significant decrease in breast cancer risk with aspirin use (RR, 0.92; 95% CI, 0.89-0.96; I 2 = 72%). Aspirin use decreased the risk of hormone receptor–positive tumors (estrogen receptor [ER]-positive RR, 0.89; 95% CI, 0.82-0.97; I2=54%; progesterone receptor [PR]–positive RR, 0.86; 95% CI, 0.78-0.95; I2=32%; ER- and PR-positive RR, 0.92; 95% CI, 0.85-1.00; I2=45%) and reduced the risk of breast cancer in postmenopausal women (RR, 0.92; 95% CI, 0.86-0.98; I2=59%). Further analysis showed that for the in situ breast cancer, regular-dose and more than 3 years use of aspirin were associated with the reduced risk of breast cancer. Conclusion This meta-analysis suggested that aspirin may reduce the overall risk of breast cancer, reduce the risk of breast cancer in postmenopausal women, hormone receptor–positive tumors, and in situ breast cancer. Larger, multicenter clinical studies are needed to find the optimal dose range, frequency, and duration of the aspirin use to explore the best benefit–risk ratio.

Background Stressful life events as important stressors have gradually been recognized as the potential etiology that may lead to adverse birth outcomes such as preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). However, researches on this topic have shown relatively inconsistent results. This systematic review and meta-analysis was performed to synthesize available data on the association between prenatal stressful life events and increased risks of PTB, LBW, and SGA. Methods Electronic databases were searched from their inception until September 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to assess the association between prenatal stressful life events and PTB, LBW, and SGA using random effects models. In addition, subgroup analyses, cumulative meta-analyses, sensitivity analyses, and publication bias diagnosis were conducted. STATA 14.0 was applied for statistical analyses. Results Totally 31 cohort studies involving 5,665,998 pregnant women were included. Prenatal stressful life events were associated with a 20% higher risk of PTB (RR = 1.20, 95%CI = 1.10-1.32), a 23% increased risk for LBW (RR = 1.23, 95%CI = 1.10-1.39), and a 14% higher risk of SGA (RR = 1.14, 95%CI = 1.08-1.20). Sensitivity analysis indicated the results were stable. Conclusions Findings indicated that pregnant women experiencing prenatal stressful life events were at increased risk of PTB, LBW, and SGA. This information provided additional supports that pregnant women experiencing prenatal stressful life events would benefit from receiving assessment and management in prenatal care services.

Summary Purpose The association between famine exposure and type 2 diabetes (T2DM) remains controversial. A meta-analysis was performed to clarify the relation of famine exposure to T2DM risk in detail. Methods A systematic literature search was performed in PubMed, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform and China Science and Technology Journal VIP Database. The articles were limited to be available in English or Chinese before 10 April 2019. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of famine exposure on T2DM. The I square value (I2) was used to assess heterogeneity, and the random effects model (REM) was adopted as the pooling method. Results This meta-analysis included 24 published articles with 1,660,385 subjects. A significant association of famine exposure with increased risk of T2DM was observed (RR = 1.433, 95% CI: 1.101–1.865). The pooled RRs were different in terms of publication year, location, study design, sample size, famine duration and definition of diabetes (criteria). Longer the famine exposure experienced, greater the effect of famine exposure on T2DM would be. Compared to WHO criteria, studies of which diabetes diagnosed by ADA criteria and other criteria might more likely to find this association. Compared to moderate famine exposure, the pooled RR in severe famine was statistically significant. Furthermore, the pooled RR adjusted for the most confounders in females was 1.517 (95% CI: 1.018–2.261). In terms of period of famine exposure, compared to adult exposure, people who exposure famine in fetal, childhood, and adolescent were likely to be diabetes. Conclusion Famine exposure may increase the risk of T2DM. The risk may vary with famine duration, definition of diabetes, gender and period of famine exposure.

This meta-analysis aimed to clarify the relationship between particulate matter (PM) and autism spectrum disorder (ASD) in detail.A systematic literature search was performed using eight databases before April 9, 2022. The estimated effects were combined separately according to the PM type. Subgroup analyses were conducted in terms of the study design type, study location, exposure window, birth year, and sex.PMExposure to PM

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers worldwide. Therefore, the potentially deleterious effect of OPE on human beings deserves extensive attention. The primary objective of this present study was to untangle the relationship between OPE exposure and cardiovascular disease (CVD) among general population. Detailed information about participants' baseline characteristics, involving socioeconomic data, demographic data and key covariates was obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Multivariate logistic regression models with adjustment for prior-determined covariates were utilized to examine the relationship between various OPEs and CVD among US adults and calculate odd ratios (ORs) and corresponding confidence intervals (CIs). Two multi-pollutant statistical strategies (weighted quantile sum regression and Bayesian kernel machine regression) were employed to investigate the joint effect of OPE mixture on CVD. A total of 5067 participants were included in this study. In completely-adjusted logistic model, the highest tertiles of OPE metabolites were positively associated with CVD risk, while the relationships did not reach statistical significance. The weighted quantile sum (WQS) index was significantly correlated with increased prevalence of CVD (adjusted OR: 1.25; CI: 1.02, 1.53, p value = 0.032) and Diphenyl phosphate (DPHP) was the greatest contributor (31.38%). The BKMR also indicated that mixed OPE exposure associated with an increased risk of CVD. Taken together, the present study demonstrated that there were possible links between OPE exposures and increased risk of CVD, while the relationships did not reach statistical significance. Our study provided the suggestive evidence that cumulative effect of OPE mixtures on CVD. DPHP may be a major driver of this positive association. Given the limitation of cross-sectional design and relatively limited kinds of OPE metabolites, further studies are warranted to longitudinally evaluate the potential effect of a wider range of OPEs on CVD or cardiac metabolism.

This study aimed to examine associations of the impact of COVID-19 pandemic on family life with emotional and behavioral health among preschool children.A longitudinal study including 1595 preschool children aged 3-6 years and their families was conducted in Anhui Province. The linear regression was applied to examine associations between the impact of COVID-19 pandemic on family life and emotional and behavioral health.Results of the multivariable linear regression indicated that the severe impact of COVID-19 pandemic on family life was significantly associated with more sleep problems, poor dietary behavior habits, more anxiety symptoms, and more problematic behaviors; and these effects exhibited gender and age differences.The severe impact of COVID-19 pandemic on family life significantly increased the risk for exacerbated emotional and behavioral health among preschool children. It is considered vital to identify risk factors for vulnerable families and then to implement precise interventions when necessary for emotional and behavioral health of children in these families.

Growing developments in engineered nanomaterials (NMs) and their wide applications inevitably raise environmental and human health concerns. Upon contact with biological fluids, NMs can attract proteins onto their surfaces to form dynamic layers called protein corona. Such new biological identities are what the bio-systems “see” and react with. Formation of protein corona around NMs determines the biological behavior of NMs and the transformation patterns of proteins. Therefore, characterization of the protein corona on NMs' surface is the first step towards understanding the nature of NMs-mediated biological effects. In this review, the roles of protein corona in NMs' bio-application and biosafety were summarized, with an emphasis on methods for characterizing NMs-protein interactions and the dynamic biological identities. Moreover, we extrapolated the discussion to environmentally relevant nanoparticles (e.g. PM 2.5) and macromolecules, and discussed the possible methods and challenges for studying their interactions with proteins.

The structural identification as well as quantitative analysis of transformation and degradation (T/D) products of tetrabromobisphenol A (TBBPA) and its derivatives can provide useful information on the corresponding T/D mechanism as well as environmental impact. However, it is still a great challenge to analyze trace levels of T/D products, both unknown and known products, as a result of the complexity of environmental matrices and the lack of commercial/artificial standard chemicals. This critical review summarized the T/D model experiments, sample preparation and the associated analytical methods, including extraction, purification, concentration, derivatization, quantitation analysis and 14C-labeling technologies. Furthermore, the mass spectral analysis of TBBPA related compounds using different analytical instruments and T/D products predicted by computer programs are also described.

Human uptake abundance of microplastics via various pathways, and they accumulate in human liver, kidney, gut and even placenta (especially with a diameter of 1 μm or less). Recent scientific studies have found that exposure to microplastics causes intestinal inflammation and liver metabolic disorder, but it remains largely unknown that whether the damage and inflammation may cause further development of severe diseases. In this study, we discovered one of such potential diseases that may be induced by the exposure to small-sized microplastics (with a diameter of 1 μm) performing a multi-organ and multi-omics study comprising metabolomics and microbiome approaches. Unlike other animal experiments, the dosing strategy was applied in mice according to the daily exposure of the highly exposed population, which was more environmentally relevant and reflective of real-world human exposure. Our studies on the gut-liver axis metabolism have shown that the crosstalk between the gut and liver ultimately leaded to insulin resistance and even diabetes. We proactively verified this hypothesis by measuring the levels of fasting blood glucose and fasting insulin, which were found significantly elevated in the mice with microplastics exposure. These results indicate the urgent need of large-scale cohort evaluation on epidemiology and prognosis of insulin resistance after microplastics exposure in future.

Although the abiotic and biotic transformation/degradation (T/D) processes of tetrabromobisphenol A (TBBPA) have been widely investigated in model experiments, few reviews have focused on these processes along with their metabolites or degradation products. In this paper, we summarize the current knowledge on the T/D of TBBPA and its derivatives, including abiotic and biotic T/D strategies/conditions, mechanisms, metabolites and environmental occurrences. Various treatments, such as pyrolysis, photolysis, chemical reactions and biotransformation, have been employed to study the metabolic mechanism of TBBPA and its derivatives and to remediate associated contaminated environments. To date, more than 100 degradation products and metabolites have been identified, dominated by less brominated compounds such as bisphenol A, 2,6-dibromo-4-isopropylphenol, 2,6-dibromo-4-hydroxyl-phenol, 2,6-dibromophenol, isopropylene-2,6-dibromophenol, 4-(2-hydroxyisopropyl)-2,6-dibromophenol, etc. It can be concluded that the T/D of TBBPA mainly takes place through debromination and β-scission. In some environmental media and human and animal tissues, brominated metabolites, glucoside and sulfate derivatives are also important T/D products. Here, the T/D products of TBBPA and its derivatives have been most comprehensively presented from the literature in recent 20 years. This review will enhance the understanding of the environmental behaviors of TBBPA-associated brominated flame retardants along with their ecological and health risks.

Background: During the current Coronavirus Disease 2019 (COVID-19) pandemic, diabetic patients face disproportionately more. Anti-inflammatory effects of hypoglycemic agents have been reported, and their effects in patients with diabetes and COVID-19 remain controversial. This study was performed to clarify this association. Methods: Relevant literature was searched on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese periodical service platform VIP Database, Sinomed (China Biology Medicine, CBM), MedRxiv, PubMed, ScienceDirect, Web of Science, Ovid Databases (LWW), Springer Link, Wiley Online Library, Oxford Academic, Nature Press Group, Cochrane Library, and BMJ Evidence-Based Medicine up to November 14, 2020. Only observational studies of hypoglycemic agents vs. other drugs or therapy in adult diabetic patients with COVID-19 were included. Data of death and poor composite outcomes were extracted. The pooled effects of hypoglycemic agents on mortality and poor composite outcomes of COVID-19 in diabetic patients, pooled ORs along with 95% CIs, were calculated using the fixed-effects or random-effects models based on heterogeneity assessment. Registration number of PROSPERO is CRD42020221951. Findings: 16 studies were included in the qualitative analysis and 14 studies with 13,371 patients were included in quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality in diabetic patients with COVID-19 (pooled OR=0·56, 95% CI, 0·39-0·81, p=0·002), especially home use of metformin (pooled OR=0·60, 95%CI, 0·40-0·88, p=0·01). but in-hospital use of metformin was associated with statistically non-significant lower mortality (pooled OR=0·44, 95%CI, 0·15-1·33, p=0·14) or poor composite outcomes (pooled OR=0·93, 95% CI, 0·79-1·11, p=0·44). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR=0·63, 95% CI, 0·26-1·56, p=0·32) or poor composite outcomes of COVID-19 in diabetic patients (pooled OR=0·96, 95% CI, 0·74-1·26, p=0·78). Interpretation: Home use of metformin might be beneficial in decreasing mortality in diabetic patients infected with SARS-CoV-2. There is insufficient evidence to conclude that metformin and other hypoglycemic agents are associated with poor composite outcomes. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. Funding Statement: This study is financially supported by Hunan Provincial Key Laboratory of Clinical Epidemiology (grant number: 2020ZNDXLCL002). Declaration of Interests: We declare no competing interests.

Natural mercury-containing nanoparticles (Hg-NPs) have been found in the environment, but the information for Hg-NPs in organisms was still limited. Clarifying the unique roles of Hg-NPs in organisms is crucial to fully understand the health risks of Hg. Herein, liver and muscle tissues of cetaceans were collected to identify the presence and characteristics of Hg-NPs. We found that methylmercury (MeHg) was the dominant species of Hg in muscles, while inorganic Hg (IHg) accounted for 84.4-99.0% (average 94.0%) of Hg in livers. By using transmission electron microscopy (TEM), size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICPMS) and single particle ICPMS (sp-ICPMS), large amounts (9-161 μg/g) of Hg-NPs in livers and small amounts (0.1-0.4 μg/g) in muscles were observed, indicating that Hg-NPs was an important form of Hg in livers. Both small sized (5-40 nm) and large sized (>100 nm) Hg-NPs were identified, which were mainly complexed with selenium (Se) and sulfur (S) as well as a few cadmium (Cd), lead (Pb) and silver (Ag). This study provided direct evidence of Hg-NPs in marine mammals as well as their chemical form and size distribution, which are helpful for further understanding the biogeochemical cycle and health risk of Hg.

Aims Although two meta-analysis have reported no association between the tumor necrosis factor-α (TNF-α)-308G/A polymorphism and susceptibility to pre-eclampsia (PE), recent studies showed the association was still controversial. Thus, we conduct an updated meta-analysis to elucidate this association. Methods Studies related to TNF-α-308G/A and PE risk were retrieved from PubMed, the Web of Science, Embase, Cochrane Library, CNKI, Wanfang, CBM, VIP Database. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated to estimate the association between the TNF-α-308G/A polymorphism and susceptibility to PE under the models of allelic contrast (A vs. G), recessive (AA vs. AG+GG), dominant (AA+AG vs. GG), and co-dominant (AA vs. GG). Results 22 studies (including 2459 cases and 4246 controls) were included in the meta-analysis. The overall analysis indicated that the significant association between TNF-α-308G/A polymorphism and susceptibility to pre-eclampsia existed in allele model (A vs. G: OR = 1.37, 95%CI: 1.06–1.77), but not in dominant model, recessive model, and co-dominant model. In subgroup analysis by ethnicity, pre-pregnancy BMI and pregnancy parity, the results showed the significant association between TNF-α-308G/A polymorphism and the risk of PE was obvious in Caucasian (A vs. G: OR = 1.36, 95%CI: 1.13–1.64; AA vs. GG: OR = 1.71, 95%CI: 1.03–2.86; AA+AG vs. GG: OR = 1.32, 95%CI: 1.03–1.71), Iranian (A vs. G: OR = 4.28, 95%CI: 2.01–9.11), and primipara (A vs. G: OR = 1.49, 95%CI: 1.15–1.92; AA vs. GG: OR = 2.15, 95%CI: 1.10–4.21). Conclusion Current evidence demonstrates that carriers of TNF-α (308A) allele would increase the susceptibility to PE, especially among Caucasian, Iranian and primipara.

Selenium (Se) is commonly recognized as a protective element with an antagonistic effect against mercury (Hg) toxicity. However, the mechanisms of this Hg–Se antagonism are complex and remain controversial. To gain insight into the Hg–Se antagonism, a type of unicellular eukaryotic protozoa (Tetrahymena malaccensis, T. malaccensis) was selected and individually or jointly exposed to two Hg and three Se species. We found that Se species showed different toxic effects on the proliferation of T. malaccensis with the toxicity following the order: selenite (Se(IV)) > selenomethionine (SeMeth) > selenate (Se(VI)). The Hg–Se antagonism in Tetrahymena was observed because the joint toxicity significantly decreased under co-exposure to highly toxic dosages of Hg and Se versus individual toxicity. Unlike Se(IV) and Se(VI), non-toxic dosage of SeMeth significantly decreased the Hg toxicity, revealing the influence of the Se species and dosages on the Hg–Se antagonism. Unexpectedly, inorganic divalent Hg (Hg2 +) and monomethylmercury (MeHg) also displayed detoxification towards extremely highly toxic dosages of Se, although their detoxifying efficiency was discrepant. These results suggested mutual Hg–Se detoxification in T. malaccensis, which was highly dependent on the dosages and species of both elements. As compared to other species, SeMeth and MeHg promoted the Hg–Se joint effects to a higher degree. Additionally, the Hg contents decreased for all the Hg–Se co-exposed groups, revealing a sequestering effect of Se towards Hg in T. malaccensis.

A novel, competitive, enzyme-linked immunosorbent assay (ELISA) was presented in this paper based on the inhibition of catalysis of AuNCs@BSA triggered by dissolved Ag+ for the detection of dibutyl phthalate (DBP). In the immunoassay system, numerous Ag+ was released from AgNPs (labelled on the second antibody, AgNPs@Ab2) in the presence of H2O2 after the competition step, preventing AuNCs@BSA from inducing a color change of 3,3',5,5'-tetramethylbenzidine (TMB) to blue. Due to the signal amplification by the principle, the sensitivity of the modified ELISA was improved with the low limit of detection (LOD) of 4.017μg/L for DBP, which was decreased 16 times relative to that using conventional ELISA with the same antibody. In addition, the established method showed satisfactory accuracy and reliability (recoveries, 85.75-117.73%; CV, 1.33-6.79%) in spike-recovery analysis. To the best of our knowledge, this is the first time that AuNCs@BSA has been used in ELISA as a peroxidase-like catalyst. Our method shows great potential for trace DBP detection from environmental and food samples.

This study aimed to explore the association between caregivers’ anxiety and sleep disturbances of preschool children aged from 3 to 6 years in rural areas of Anhui province, China. Besides, we also explored whether there is a mediated effect of resilience on this association. Caregivers of children from 26 kindergartens completed a structured questionnaire, the Children’s Sleep Habits Questionnaire (CSHQ), Self-rating Anxiety Scale (SAS) and the Devereux Early Childhood Assessment for Preschoolers, Second Edition (DECA-P2). CSHQ, SAS and DECA-P2 were used to evaluate sleep disturbances among preschool children, the caregivers’ anxiety, and the resilience of preschool children respectively. A total of 3,802 questionnaires were distributed in our investigation, after checking for completeness, 166 invalid questionnaires were excluded and 3,636 questionnaires were eventually included in our study. Binary logistic analysis was utilized to explore the potential relationship between caregivers’ anxiety and sleep disturbances of children. Moderating effect of resilience was evaluated through calculating the percentage of change in odds ratios (OR) in the models with and without resilience. 10% or more of percentage change in OR was defined as a significant mediation effect. In our study, 89.4% of the preschool children aged from 3 to 6 years had potential sleep disturbances. In preschool children whose caregivers are their parents, the correlation between caregivers’ anxiety and sleep disturbances of preschool children is statistically significant (OR = 10.168,95 %CI:2.506–41.263). In preschool children whose caregivers aren’t their parents, the correlation is also significant (OR = 2.405,95 %CI:1.139–5.077). Furthermore, resilience could attenuate the association between caregivers’ (including parents and other relatives) anxiety and sleep disturbances amongst preschool children. After adjusting resilience, the association between caregivers’ anxiety and sleep disturbances of preschool children was attenuated and remained significant (OR for parents = 9.323,95 %CI:2.295–37.875; OR for other caregivers = 2.232,95 %CI:1.050–4.745). In specific sleep domain of CSHQ, the moderating effect of resilience significantly existed in sleep duration and daytime sleepiness. Our study indicated that caregivers’ anxiety was associated with sleep disturbances among preschool children. High resilient children may be partly protected against the negative effect of caregivers’ anxiety on their sleep quality. Future well-designed cohort studies are needed to further explore this topic in more details.

Inorganic divalent mercury complexes (Hg2+) and monomethylmercury complexes (MeHg) are the main mercury species in aquatic systems and their toxicity to aquatic organisms is of great concern. Tetrahymena is a type of unicellular eukaryotic protozoa located at the bottom of food chain that plays a fundamental role in the biomagnification of mercury. In this work, the dynamic accumulation properties, toxicological characteristics and mechanisms of Hg2+ and MeHg in five Tetrahymena species were evaluated in detail. The results showed that both Hg2+ and MeHg were ingested and exhibited inhibitory effects on the proliferation or survival of Tetrahymena species. However, the ingestion rate of MeHg was significantly higher than that of Hg2+. The mechanisms responsible for the toxicity of MeHg and Hg2+ were different, although both chemicals altered mitochondrial membrane potential (MMP). MeHg disrupted the integrity of membranes while Hg2+ had detrimental effects on Tetrahymena as a result of the increased generation of reactive oxygen species (ROS). In addition, the five Tetrahymena species showed different capacities in accumulating Hg2+ and MeHg, with T. corlissi exhibiting the highest accumulations. The study also found significant growth-promoting effect on T. corlissi under low concentration exposure (0.003 and 0.01μg Hg/mL (15 and 50nM)), suggesting different effect and mechanism that should be more closely examined when assessing the bioaccumulation and toxicity of mercury in aquatic ecosystems.

Bisphenol A (BPA) and its analogs (bisphenol F, BPF; bisphenol AF, BPAF; bisphenol S, BPS; and tetrabromobisphenol A, TBBPA) are transported by blood and bind estrogen receptors of target organs or cells. They were confirmed to bind human serum albumin (HSA) in blood, and the binding constants of BPA (5.14 × 103 M−1), BPF (1.05 × 104 M−1), and BPS (7.89 × 103 M−1) determined via equilibrium dialysis shows moderate binding ability with multiple binding sites. The HSA-water partition coefficients (log KHW > 3) are greater than their octanol-water distribution coefficients, and may follow the order: TBBPA > BPAF > BPA (3.75) > BPF (3.61) > BPS (3.27). Functional groups and substitutions of bisphenols (BPs) determine the fluorescence quenching of Trp214 in HSA. The effects follow: TBBPA (4.41 × 1014 M−1 s−1) » BPS (4.08 × 1012 M−1 s−1) > BPAF (1.20 × 1012 M−1 s−1) > BPF (3.06 × 1011 M−1 s−1) ≈ BPA (4.47 × 1011 M−1 s−1), which is in line with the molecular docking results. In this process, the enzymatic characteristics of HSA were changed simultaneously, as evidenced by decreased Km and Vmax except for BPS (increased Km and Vmax) and increased catalytic efficiency, which may improve the hydrolysis of other drugs. However, the native conformation of the protein underwent locally adaptive changes due to the reversible binding. Overall, these data provide a mechanistic explanation for the transport of BPs in human blood, which may affect their retention and toxicity.

Black phosphorus nanosheets (BPs) belong to a type of two-dimensional layered materials and have garnered significant attention due to their diverse potential in nanomedical applications. Until recently, BPs have been increasingly applied in the biomedical field due to their excellent physical and chemical properties, as well as good biocompatibility. However, there has not been much concern about their potential toxic effects or biological effects on physiological systems. Herein, we found that BPs induced a reversible inflammatory response in mice, and then the detailed multifactorial inflammatory effects were studied among mouse macrophages. The treatment with BPs can induce higher levels of reactive oxygen species (ROS) in mouse bone marrow-derived macrophages (BMDMs), leading to significant changes in cell survival rate, apoptosis, and inflammatory cytokines. The molecular levels of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and nitric oxide (NO) in the treated cells were evaluated. The results indicated a significant increase in the expression of these molecules, suggesting an expansion of inflammatory reactions. The protein expression of heme oxygenase-1 (HO-1) molecules was decreased in BP-treated groups of cells, which indicates that BPs may inhibit anti-inflammatory effects of cells, leading to aggravation of inflammation. These findings provide evidence for biointeractions of BPs in physiological systems and may be helpful for the safe use of BP-based therapies.

With the potential biomedical applications of nanomaterials such as silver nanoparticles (SNPs), nanotoxicity concerns are growing, and the importance of NP and protein interactions is far from being addressed enough. Here, we identified the major binding protein on SNPs in blood as human serum albumin (HSA) using polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. By comparing with the previous methods, we emphasized surface area concentration as a new dose metric to address the importance of NP curvature. SNPs interacted with cysteine and cystine, disrupting the secondary structure and conformation of HSA, and this tendency became stronger on small SNPs than large ones. The protein corona significantly alleviated the toxicity and decreased SNPs' internalization in a particle size-dependent manner, where more significant inhibition effects occurred on larger particles at the same area concentration. These findings may shed light on nanotoxicity and also the design of safe nanomaterials by a comprehensive preconsideration of the metrological method.

Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA DHEE), as one of the TBBPA derivatives, is frequently applied as a flame retardant. To date, however, little evidence has been gathered regarding its environmental behavior and fate. This is mainly attributed to the lack of an analytical approach available to measure it. Mass spectrometry cannot determine levels of TBBPA DHEE. LC-MS could not ionize TBBPA DHEE to yield enough fragments, while GC-MS could not be applied for the analysis either, due to the thermal degradation of TBBPA DHEE. We here designed a novel hapten, then conjugated it with a carrier protein and produced a type of polyclonal antibody capable of recognizing TBBPA DHEE. Based on this approach, a sensitive and high-throughput indirect competitive enzyme-linked immunosorbent assay (ELISA) was established. The respective detection limit (LOD, based on 90% B/B0) and IC50 calculated from the standard curve were 0.702 and 9.868 ng/mL for TBBPA DHEE. And the established method showed good tolerance to various matrix interferents. Using our ELISA, we measured the concentrations of these substances from environmental water samples with no pretreatment other than filtration. We found the presence of TBBPA DHEE in environmental water samples collected in Jiangsu province, and the detected concentrations ranging from 1.5 to 7.7 ng/mL. Our proposed method here could be applied to completely and systematically investigate TBBPA DHEE and TBBPA MHEE concentrations in environmental samples.

Selective adsorption via the size matching effect is one of the most effective strategies for separating and analyzing low levels of organic molecules. Herein, multicomponent covalent organic frameworks (MC-COFs) with tunable pore sizes are constructed by using one knot (1,3,5-triformylphloroglucinol, Tp) and two organic linkers (p-phenylenediamine, Pa; benzidine, BD). The pore sizes of the MC-COFs composed of TpPaBDX (X = [BD]/([Pa] + [BD]) × 100 = 0, 25, 50, 75, and 100) range from 0.5–1.5 to 0.5–2.2 nm due to variations in the initial organic linker ratios. When coupling TpPaBDX-based solid-phase microextraction (SPME) with constant flow desorption ionization mass spectrometry (CFDI-MS), these MC-COFs feature better selective adsorption performance for tetrabromobisphenol A (TBBPA) derivatives than TpPa with a smaller pore size, TpBD with a larger pore size and even some commercial fibers (e.g., polydimethylsiloxane/divinylbenzene (PDMS/DVB)-, polyacrylate (PA)- and PDMS-coated fibers). The improved method involving MC-COF TpPaBD50 also presents favorable stability with relative standard deviations (RSD, 1 μg L−1) for single fibers of 5.5–7.9% (n = 7) and fiber-to-fiber of 6.6–7.8% (n = 7). Due to the decreased limits of detection and quantification (0.5–12 and 1.6–40 ng L−1), and reduced separation and detection time (7 min), ultratrace levels of TBBPA derivatives in real water samples are successfully detected. The proposed method shows great potential for the rapid tracing of the distribution, transportation and transformation of TBBPA derivatives to better understand their ecotoxicological effects in environmental media.

Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant. TBBPA and its alternative, tetrabromobisphenol S (TBBPS), are the reactive chemicals used to produce TBBPA/S derivatives. The manufacturing and application of TBBPA/S derivatives may result in their accumulation in environmental compartments and may cause risks to environmental safety and human health. To investigate the occurrence and transformation products of TBBPA/S and TBBPA/S derivatives, it is imperative to develop effective sample preparation and sensitive analytical methods for various environmental matrices. In this paper, we summarize the techniques for analysis of TBBPA/S and their derivatives. We also critically review methodologies for the identification of unknown metabolites transformed from these chemicals. In the perspective section, we discuss trends in analytical strategies for studying emerging TBBPA/S derivatives.

With the wide application of nanosilver or silver nanoparticles (AgNPs) in a diverse spectrum of fields, the environmental exposure of this kind of nanomaterial has become inevitable. Lots of attention was paid to its potential adverse effects based on multiple experimental models; nevertheless, the translocation, distribution, and possible biotransformation of nanosilver in organisms are the essential prerequisites for its biological effects. This work focused on this point and provided a comprehensive review of the behavior of nanosilver in multiple mammals, in view of its administration routes, biouptake, translocation, biodistribution, bioaccumulation, biotransformation, elimination, and retention. The regulatory factors for the bioavailability of nanosilver included the characteristics of the nanoparticle per se and the ambient condition. This review brings insights on the biological processes of nanosilver and may help explain its potential effects on mammals, including human beings.

Environmental distribution and concentration of tetrabromobisphenol A bis- (2-hydroxyethyl) ether (TBBPA-DHEE) and tetrabromobisphenol A mono- (hydroxyethyl) ether (TBBPA-MHEE), are obscure due to the lack of available analytical methods. Here two novel immunoassays were established to systematically investigate their distributions in Taizhou, Eastern China. Five monoclonal antibodies against pollutants were generated with two designed haptens through animal immunization. After matched with different coating antigens/antibodies, ELISAs were established (LOD for TBBPA-DHEE, 0.12 ng/mL, based on OVA-M3/mAb-D4G6; LOD for TBBPA-MHEE, 0.79 ng/mL, based on OVA-M3/mAb-D2G6) and applied for investigation of their occurrences at a typical e-waste recycling area after 2-year samples collection, where the total 33 water, 32 soil and 16 biological samples were collected with the highest concentrations of 3.46 ng/mL, 2.76 ng/g (dry weight, dw) and 5.01 ng/g (dw), respectively. Meanwhile, our study also indicated that at the centralizing e-waste recycling sites the serious pollution for both chemicals still existed despite of various efforts. Besides, obvious improvements were observed at an abandoned e-waste recycling region treated and remedied for many years by the local Chinese government. These findings highlight the importance of policy decisions in treatment of pollutants to reduce organic pollutant-related health risks.

Widespread environmental contamination of legacy long-chain poly- and per-fluoroalkyl substances (PFASs) has triggered chemical regulatory action and a global transitioning to alternative PFASs. More than 5000 PFASs are now recognized on various lists, but few have been monitored despite ample evidence of unidentified organic fluorine in human and environmental samples. Nevertheless, our review of the literature indicates that nontarget analytical methods based on high-resolution mass spectrometry have been used to discover more than 750 PFASs, belonging to more than 130 diverse classes, in strategically selected environmental samples, biofluids or commercial products. Among these reports, we summarize the analytical and data-processing strategies for nontarget PFAS discovery, identify knowledge gaps and propose new areas for method development. Discovery of emerging PFASs before they are global contaminants could mitigate future contamination if strategic techniques can be developed to prioritize some of these substances for synthesis and confirmation, further monitoring, source elucidation and hazard characterization.

Sensitive detection of tetrabromobisphenol A (TBBPA) and its derivatives, a group of emerging toxic contaminants, is highly necessitated in environmental investigation. Herein a novel analytical strategy based on reactive extractive electrospray ionization (EESI) tandem mass spectrometry for detection of tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE), tetrabromobisphenol A bis(glycidyl ether) (TBBPA-BGE), tetrabromobisphenol A bis(allylether) (TBBPA-BAE), and tetrabromobisphenol S bis(allylether) (TBBPS-BAE) in industrial waste water samples was developed. Active silver cations (Ag(+)), generated by electrospraying a silver nitrate methanol solution (10 mg L(-1)), collides the neutral TBBPA derivatives molecules in the EESI source to form [M+Ag](+) complexes of the analytes under the ambient conditions. Upon collision-induced dissociation (CID), characteristic fragments of the [M+Ag](+) complexes were identified for confident and sensitive detection of the four TBBPA derivatives. Under the optimized experimental conditions, the instrumental limits of detection (LODs) of TBBPA-BHEE, TBBPA-BGE, TBBPA-BAE and TBBPS-BAE were 0.37, 0.050, 0.76, and 4.6 μg L(-1), respectively. The linear ranges extended to 1000 μg L(-1) (R(2)≥0.9919), and the relative standard deviations (RSDs), inter-day variation and intra-day variation were less than 7.8% (n=9), 10.0% (n=5), and 14.8% (n=1 per day for 5 days) for all derivatives. TBBPA derivative manufacturing industrial waste water, river water and tap water samples were fast analyzed with the proposed method. The contents of TBBPA derivatives were various in the collected samples, with the highest 19.9±0.3 μg L(-1) of TBBPA-BAE in the waste water samples.

Graphene oxide (GO) displays promising properties for biomedical applications including drug delivery and cancer therapeutics. However, GO exposure also raises safety concerns such as potential side effects on health. Here, the biological effects of GO suspended in phosphate buffered saline (PBS) with or without 1% nonionic surfactant Tween 80 were investigated. Based on the ex vivo experiments, Tween 80 significantly affected the interaction between GO and peripheral blood from mice. GO suspension in PBS tended to provoke the aggregation of diluted blood cells, which could be prevented by the addition of Tween 80. After intravenous administration, GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system. Nevertheless, GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80. In contrast, less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension. Organs including hearts, livers, lungs, spleens, kidneys, brains, and testes did not reveal histological alterations. The indexes of peripheral blood showed no change upon GO exposure. Our results together demonstrated that Tween 80 could greatly alter GO's biological performance and determine the pattern of its biodistribution in mice.

Primitive e-waste dismantling activities have been of increasing concern due to serious environmental and human health problems, and therefore authorities in China have strengthened the regulations on illegal e-waste recycling activities. In this work, we used rice hull as a passive sampler and investigated temporal trends of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) in areas near e-waste recycling sites after the stricter regulations. Furthermore, the distribution patterns and composition profiles of these contaminants were also discussed. The average concentrations of the three groups of persistent organic pollutants (POPs) in rice hulls have markedly decreased during the period of 2005-2009. Specifically, from 12.9 (average value in 2005) to 0.37 pg WHO-TEQ/g (dry weight, dw) (in 2009) for PCDD/Fs, 47.6 (2005) to 7.10 ng g(-1)dw (2009) for PCBs, and 2.51 (2005) to 0.89 ng g(-1), dw (2009) for PBDEs. The significant decrease of combustion markers 2,3,4,7,8-PeCDF, 1,2,3,6,7,8HxCDF and PCB126, and the PCDD/PCDF ratio from 1:9 (2005) to 7:3 (2009) is likely a result of stricter regulations on open combustion activities. This study suggests that stricter control measures, strengthened laws and regulations and more environmental friendly techniques could be effective measures in reducing the release and formation of related POPs in typical e-waste dismantling sites, and these measures could further improve the quality of the environment and health of the local inhabitants.

A novel gas chromatography/high resolution mass spectrometry method coupled with multisorbent thermal desorption cartridges has been developed for the determination of volatile neutral polyfluorinated iodine alkanes (PFIs) in airborne samples. It allows, for the first time, simultaneous analysis of four mono-iodized perfluorinated alkanes, three diiodized perfluorinated alkanes and four mono-iodized polyfluorinated telomers in ambient air samples. 3.75 L air sample was passed through a sorbent tube packed with 150 mg of Tenax TA and 200mg of Carbograph 1 TD for analyte adsorption. Important factors during the analysis procedures, such as safe sampling volume, air sampling rate, analyte desorption and transfer strategies, were optimized and good thermal desorption efficiencies were obtained. The method detection limit (MDL) concentration ranged from 0.04 pg/L for 1H,1H,2H,2H-perfluorododecyl iodide to 1.2 pg/L for perfluorohexyl iodide, and instrument response of a seven-point calibration was linear in the range of 10-1000 pg. Travel spike recoveries ranged from 83% to 116%. Small variabilities of less than 36% were obtained near the MDLs and the differences between triplicates were even smaller (2.1-7.3%) at 200 pg spiked level. The method was successfully applied to analyze ambient air samples collected near a point source, and five PFIs were identified (10.8-85.0 pg/L), with none of the analytes detectable at the background site.

Purified carboxylated multiwalled carbon nanotubes (MWCNTs) with different agglomeration propensities were evaluated in mice following a single dose intravenous injection. Both agglomerated and the well suspended MWCNTs were taken up by mononuclear phagocyte system organs. MWCNTs with higher degree of agglomeration were retained in lungs and later in the liver and were not eliminated completely in 28 days, while the well-dispersed ones remained well dispersed and formed fewer aggregates in the lungs and liver, and seemed to be easily eliminated. Persistent accumulation of agglomerated MWCNTs in the lungs caused inflammatory responses while the well-suspended ones did not. Although the elimination of MWCNTs is still to be evaluated quantitatively, the formation of a stable suspension is one of the key requirements for safe applications in medicine.