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Perfluorooctanesulfonic acid (PFOS) is an emerging environmental organic pollutant that has been widely used in daily life products in the last century. Numerous studies showed that the accumulation of PFOS in human through food chain would lead to various disease. However, there is currently no report about its in situ localization in the tissue. In present study, we aimed to develop a reproductive and less-cost method to quantitatively detect and determine the spatial distribution of PFOS in mouse kidney by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) with a commercially available matrix. α-Cyano-4-hydroxycinnamic acid (CHCA) matrix was optimized for PFOS detection in MALDI-IMS analysis. Compared to other organic matrices, CHCA used in negative ion mode showed less background interference and enhanced MS signal intensity and high spatial resolution (80 μm) for PFOS analysis. The use of a CHCA matrix with an autospray system led to successful identification of the PFOS ion signals on the perfusion kidney tissue. The detection limit was at the μg/mL level, with direct visualization from a MS image. The developed method with the optimized parameters was successfully employed to obtain the PFOS spatial distribution in the kidney collected from mice after the PFOS exposure for 14 days. PFOS was mainly distributed in the kidney cortex region, which was consistent with the histological analysis results. Taken together, a rapid, economic, and efficient method was developed for PFOS detection by MALDI-IMS using a CHCA matrix. Mapping the distribution of PFOS by MALDI-IMS with a CHCA matrix provides an innovative approach for the analysis of environmental pollutants in animal or human tissues.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used in manufacturing consumer products to replace the use of bisphenol A (BPA), but exposure data are limited, particularly among pregnant women. Here, we measured BPA, BPS, and BPF levels in urine samples, collected from 941 pregnant women over three trimesters. We examined the correlations, coexposure patterns, variability, and predictors of bisphenols using Spearman's correlation coefficient, percentile analysis, intraclass correlation coefficient, and linear mixed models, respectively. We assessed health risks using average concentrations of bisphenols over three trimesters. The three bisphenols were detected in more than 50% of samples, among which BPA was the predominant one. Cashiers, office workers, teachers, and salespersons had elevated urinary BPS concentrations, while healthcare workers had relatively higher BPA concentrations. About 15 participants had potential health risks induced by exposure to bisphenol mixtures. These findings indicate that exposure to multiple bisphenols at low levels is common over three trimesters. Multiple measurements of urinary BPA and BPS concentrations are needed for more accurate evaluation of the exposure levels during pregnancy, while urinary BPF concentrations during pregnancy are moderately reliable. Occupational exposure should be taken into consideration in future demographic studies.

A method for the analysis of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in serum was developed using gas chromatography coupled to tandem mass spectrometry with atmospheric pressure chemical ionization (GC-APCI-MS/MS). The ionization and fragmentation performance of APCI were evaluated and compared with those of electron ionization (EI). In contrast to extensive fragmentation caused by EI with high energy, soft ionization achieved by APCI produced mass spectra dominated by molecular ions from the first stage of MS analysis. Better sensitivity and selectivity achieved by the GC-APCI-MS/MS method allowed to analyze serum samples with a low volume (100 μL). The limits of detection (LODs) ranged from 0.067 to 14 pg/mL for the analysis in serum samples. The developed method was evaluated at three spiking levels (0.05, 0.5 and 5 ng/mL for PCBs), showing good recoveries and repeatability. The recoveries ranged from 74.0% to 130.5%, and the relative standard deviations (RSDs) were less than 20%, for all analytes. The determination of PCBs and PBDEs in the human serum samples by GC-APCI-MS/MS was compared with gas chromatography-tandem mass spectrometry with EI (GC-EI-MS/MS). BDE-99 and BDE-100 were successfully quantified by GC-APCI-MS/MS, while these two PBDE congeners were not detected by GC-EI-MS/MS. The GC-APCI-MS/MS method had a clear advantage when analyzing compounds at low levels.

The 5′ end of a eukaryotic mRNA transcript generally has a 7-methylguanosine (m 7 G) cap that protects mRNA from degradation and mediates almost all other aspects of gene expression. Some RNAs in Escherichia coli , yeast, and mammals were recently found to contain an NAD + cap. Here, we report the development of the method NAD tagSeq for transcriptome-wide identification and quantification of NAD + -capped RNAs (NAD-RNAs). The method uses an enzymatic reaction and then a click chemistry reaction to label NAD-RNAs with a synthetic RNA tag. The tagged RNA molecules can be enriched and directly sequenced using the Oxford Nanopore sequencing technology. NAD tagSeq can allow more accurate identification and quantification of NAD-RNAs, as well as reveal the sequences of whole NAD-RNA transcripts using single-molecule RNA sequencing. Using NAD tagSeq, we found that NAD-RNAs in Arabidopsis were produced by at least several thousand genes, most of which are protein-coding genes, with the majority of these transcripts coming from Arabidopsis genes, over 5% of their transcripts were NAD capped. Gene ontology terms overrepresented in the 2,000 genes that produced the highest numbers of NAD-RNAs are related to photosynthesis, protein synthesis, and responses to cytokinin and stresses. The NAD-RNAs in Arabidopsis generally have the same overall sequence structures as the canonical m 7 G-capped mRNAs, although most of them appear to have a shorter 5′ untranslated region (5′ UTR). The identification and quantification of NAD-RNAs and revelation of their sequence features can provide essential steps toward understanding the functions of NAD-RNAs.

Exposure to mixtures of personal care product chemicals (PCPCs) is commonplace among the Chinese population; yet, limited data are available on the variations, determinants, and coexposure patterns of PCPCs, particularly among pregnant women at multiple time points during gestation. Here, we measured concentrations of 11 most common PCPCs (five parabens, five benzophenones, and triclosan) in 2823 urine samples collected from 941 pregnant women over three trimesters. Based on the quantification results, we calculated the intraclass correlation coefficient (ICC) to assess within-person variability of targeted compounds, applied linear mixed mode models to explore associations between urinary concentrations of PCPCs and exposure-related factors, and used percentile analysis to evaluate exposure to specific or multiple chemicals at one or three trimesters. Seven targeted compounds: methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), 4-hydroxybenzophenone (4-OH-BP), 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3), and triclosan (TCS) were detected in over 66% of samples. The median urinary concentrations (ng/mL) of MeP, EtP, PrP, 4-OH-BP, BP-1, BP-3, and TCS were 15.44, 0.49, 0.61, 0.16, 0.25, 0.53, and 0.48, respectively. We observed that benzophenones (ICC: 0.46-0.55) and triclosan (ICC: 0.50) were less variable than parabens (ICC: 0.35-0.40). Urinary levels of parabens were related to physical activity frequency; urinary levels of benzophenones were associated with the refurbishment of homes and household income, and urinary levels of triclosan were contingent upon the personal basic information (prepregnancy body mass index and age). Notably, higher levels of benzophenones and triclosan but lower paraben levels were observed in summer than in winter. Both coexposure to high percentiles of multiple pollutants at one trimester and exposure to one pollutant at high-dose through three trimesters were rare in the study population. Our findings suggest that these exposure-related factors should be taken into consideration, and health risks should be assessed on mixtures of pollutants in future epidemiological studies.

The development of a rodent ambient particulate matter (PM) inhalation system is critical for drawing causal inferences between PM exposure and the onset of human diseases. In this study, we constructed a real-ambient PM exposure system to investigate multi-organ injury and the reversibility of the impairments in C57BL/6 J male mice exposed to PM with a duration of up to three months in Shijiazhuang, a city with the highest PM2.5 concentration in China. This unique exposure system provided an optimal scenario for round-the-clock PM exposure absent a change in the physiochemical properties of PM and minimized the disturbance to the mice habitat. The mean concentration of PM2.5 in the exposure chambers was 89.95, 79.98, and 87.87 μg/m3 at three different time points, respectively: weeks 1–3, week 1–6, and week 1–12. The injury in multiple organs, including lung, brain, heart, testis, and intestine, was profound and was evident by the significant pathological and functional alterations. Pulmonary pathological examination revealed severe interstitial inflammatory and alveolar hemorrhage throughout the exposure, which was in line with the reduced lung function and the increased cytokine excretion in bronchoalveolar lavage fluid and blood plasma. Notably, the PM-mediated inflammatory response in different systems was correlated with the severity of the injury and the attenuation of pulmonary lesions in the recovery group. Thus, the PM2.5-induced inflammatory response, the chemical components-induced cytotoxicity, genetic damage, and oxidative stress might be implicated in the impairment of multiple murine organs. These findings revealed the severity, sensitivity, and reversibility of multi-organ injury in response to a real-ambient PM exposure.

Background: Benzophenones (BPs), parabens, and triclosan (TCS) are widely used in personal care products and may be neurotoxic to children, but limited studies have estimated the associations between exposure to these potential endocrine disrupting chemicals during pregnancy and child neurocognitive development. Objective: Our aim was to evaluate the relationships of prenatal exposure to BPs, parabens and TCS with child neurocognitive development at age 2. Methods: From 2014 to 2015, 478 mother-child pairs from a longitudinal prenatal cohort in China were included in present study. We quantified BPs, parabens and TCS in three spot urine samples during pregnancy (in the first, second, and third trimester). The Bayley Scales of Infant Development (BSID) test to children was performed at 2 years. Multivariate linear regression models and generalized estimating equations were used to examine changes in mental developmental index (MDI) and psychomotor development index (PDI) per 2-fold increase in averaged and trimester-specific maternal urinary phenols, respectively. Results: In the adjusted models, each 2-fold increase in average prenatal paraben concentration was associated with lower MDI scores among girls [−1.08 (95% CI: −2.10, −0.06) and − 1.51 (95% CI: −2.69, −0.32) for methyl paraben (Mep) and Σparabens, respectively], but the association was not statistically significant among boys [−0.24 (95% CI: −1.46, 0.99), Psex-int = 0.37 and 0.18 (95% CI: −1.28, 1.64), Psex-int = 0.10 for Mep and Σparabens, respectively]. Increasing urinary 4-hydroxybenzophenone (4-OH-BP) concentration was associated with lower PDI scores among boys [−2.96 (95% CI: −4.48, −1.45)], not girls [−0.07 (95% CI: −1.57, 1.43)] and the association was significantly different in boys and girls (Psex-int = 0.01). No significant associations were observed between the average prenatal TCS exposure and BSID results. In trimester-specific analyses, increasing parabens was associated with lower girls' MDI only in the second trimester, while increasing 4-OH-BP was associated with lower boys' PDI in each trimester. Conclusion: Our results suggest that prenatal exposure to BPs and parabens may be associated with impairment in child cognitive abilities at 2 years. Further human and animal studies are needed to verify our results and elucidate the biological mechanisms involved in these associations. Keywords: Benzophenones, Parabens, Triclosan, Child neurocognitive development

Highlighted evidence suggests the possible implication of bisphenol A (BPA) exposure on a variety of biological functions, such as DNA damage. Similar to DNA, exposed to BPA may also have potential risks to RNA damage due to its induction of reactive oxygen species. However, there are no related research reports about such health risks of BPA. Therefore, this work tried to investigate the BPA exposure induced oxidative RNA damage by detecting urinary nucleosides, the end-products of RNA metabolism. An ultra-high performance liquid chromatography-Orbitrap mass spectrometry method was applied to selectively and sensitively determine urinary nucleosides. As a result, 66 nucleosides were identified and the effects of BPA exposure on these nucleosides in rat urine samples were evaluated. The nucleosides showed different changing tendency along with different exposure dose of BPA. The strongest effect was observed in high does-exposure rats, indicating dose-response relationship between BPA-treatment and urinary nucleosides. Significant change of some nucleosides, including 8-oxoguanosine, was observed in the high-dose exposure group, suggesting obvious RNA damage to rats. To the best of our knowledge, it is the first study about the RNA damage induced by BPA exposure. The results provided a new perspective on the toxic effects of BPA exposure.

Background: Widespread exposure to parabens has been a concern, especially among pregnant women. Only one study reported that parabens are associated with glucose levels among pregnant women. However, studies on parabens exposure and gestational diabetes mellitus (GDM) are lacking. Objectives: This study investigated whether exposure to parabens in early pregnancy is related to GDM. Methods: We conducted a prospective study of 1087 pregnant women from a single tertiary medical center between 2014 and 2015 in Wuhan, China. Parabens [methyl paraben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzylparaben (BzP)] concentrations were measured in spot urine samples collected between 8 and 16 gestational weeks. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. We used the Poisson regression with a robust error variance with generalized estimating equations (GEE) estimation analyses to evaluate associations between parabens exposure and GDM risk. Results: A total of 103 (9.5%) women were diagnosed with GDM. We evaluated the associations of GDM risk with urinary MeP, EtP, and PrP (detection rate: >90%), but not with BuP and BzP due to the relatively low detection rate (

Triclosan (TCS), an extensively used antimicrobial agent, has raised considerable concern due to its hepatocarcinogenic potential. However, previous hepatotoxicity studies primarily focused on the activation of specific intracellular receptors, the underlying mechanisms still warrant further investigation at the metabolic level. Herein, we applied metabolomics in combination with lipidomics to unveil TCS-related metabolic responses in human normal and cancerous hepatocytes. Endogenous and exogenous metabolites were analyzed for the identification of metabolic biomarkers and biotransformation products. In L02 normal cells, TCS exposure induced the up-regulation of purine metabolism and amino acid metabolism, caused lipid accumulation, and disturbed energy metabolism. These metabolic disorders in turn enhanced the overproduction of reactive oxygen species (ROS), leading to the alteration of antioxidant enzyme activities, down-regulation of endogenous antioxidants, and peroxidation of lipids. TCS-induced oxidative stress is thus considered to be one crucial factor for hepatotoxicity. However, in HepG2 cancer cells, TCS underwent fast detoxification through phase II metabolism, accompanied by the enhancement of energy metabolism and elevation of antioxidant defense system, which contributed to the potential effects of TCS on human hepatocellular carcinoma development. These different responses of metabolism between normal and cancerous hepatocytes provide novel and robust perspectives for revealing the mechanisms of TCS-triggered hepatotoxicity.

Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA). An integrated method involving molecular toxicology and mass spectrometry (MS)-based global metabolomics was applied to evaluate the toxicity of TCBPA and TBBPA on cell viability, reactive oxygen species (ROS), and metabolic alterations. The results demonstrated that low micromolar levels (0–10 μM) of TCBPA/TBBPA exposure induced cell proliferation and activated the energy metabolism of both glycolysis and amino acid. On the other hand, high micromolar levels (10–50 μM) of TCBPA/TBBPA exposure perturbed the balance between ROS and antioxidative defense process by promoting the ROS generation via the down-regulation of glutathione biosynthesis and up-regulation of nucleotide metabolism. This study, for the first time, provides evidence and mechanism for better understanding the cytotoxicity of TCBPA and TBBPA by regulating the specific metabolic pathways.

Core-shell magnetic metal organic nanocrystals were synthesized and used as matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Four nitropolycyclic aromatic hydrocarbons (nitro-PAHs) were successfully detected by using negative-ion MALDI-TOF MS without background interference. Furthermore, the magnetic nanocomposites (MNCs) coated with zeolitic imidazolate framework-8 (ZIF-8) showed excellent adsorption and enrichment capacity, and can be isolated with a magnet and directly spotted on the stainless steel plate for MALDI measurement. It was also analyzed nitro-PAHs in PM2.5 samples using the ZIF-8-coated magnetic nanocomposite as adsorbent and matrix.

Exposure to airborne particulate matter (PM) 2.5 induced various adverse health effects, such as metabolic syndrome, systemic inflammation and respiratory infection. However, a global influence of PM2.5-induced metabolic and proteomic disorders remains confusing, and the underlying mechanism is still under-explored. Herein, LC-MS/MS-based metabolomics, lipidomics and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics were applied to analyze the toxicological characteristics of PM2.5 from Taiyuan City in China (Taiyuan-PM2.5) on human lung carcinoma cells (A549) after the 24-h treatment. Metabolites, lipids and proteins that have distinctive differences were screened by SIEVE, LipidSearch and Proteome Discoverer, respectively. The abundance of 56 metabolites (40 increased and 16 decreased), 22 lipids (19 increased and 3 decreased) and 81 proteins (55 up-regulated and 26 down-regulated) were significantly changed upon the PM2.5 treatment. Among the proteomics analysis, 16 proteins were specifically related to RNA splicing, mainly including up-regulated serine/arginine-rich splicing factor 1 (SRSF1), SRSF2, small nuclear ribonucleoprotein 70 kDa (snRNP70), small nuclear ribonucleoprotein polypeptide B (SNRPB), SNRPC, SNRPE and down-regulated heterogeneous nuclear ribonucleoprotein U-like 2 (hnRNP UL2). At the metabolic level, PM2.5 exposure significantly altered the sphingolipid metabolism, including ceramide, serine, sphingosine and sphingomyelin. It was proposed that excessive accumulation of ceramide and expression of key enzymes (ceramide synthases, phingomyelinase, sphingosine kinase types 2 and protein phosphatase-1) induced the secretion of pro-inflammatory cytokines, generation of lipotoxicity and alterations of RNA splicing in PM2.5-treated A549 cells. In general, our results demonstrated that ceramide accumulation and altered RNA splicing could becritical contributors to PM2.5-induced cytotoxicity at metabolic and proteomic level, which might be considered as potential markers for toxicological evaluation of PM2.5 samples.

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): −0.11, −0.01) and 0.08 cm (95% CI: −0.15, −0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted β = −27.99 g, 95% CI: −50.66, −5.31 and −19.75 g, 95% CI: −37.31, −2.19, respectively) and length (adjusted β = −0.08 cm, 95% CI: −0.17, 0.00 and −0.08 cm, 95% CI: −0.15, −0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Toxic chemicals such as flame retardants are associated with atmospheric fine particles (PM2.5), which are an important pollutant in the world. In this study, a sensitive method using gas chromatography-tandem triple quadrupole mass spectrometry combined with ultrasonic-assisted extraction and multi-phase column purification was developed for simultaneously determination of 29 flame retardants including halogenated flame retardants (HFRs) and organophosphate flame retardants (OPFRs) in PM2.5 samples. Extraction time, as well as the type and volume of elution solvent were optimized. The recoveries of all target flame retardants from PM2.5 samples were in the range of 70%‒130%, with good repeatability and reproducibility (0.39%‒17.4%). The instrumental detection limits (IDLs) and method quantitation limits (MQLs) of HFRs were in the range of 0.004‒5.44 pg and 0.002‒2.52 pg m−3, while those of OPFRs were 0.003‒0.23 pg and 0.07‒5.41 pg m−3, respectively. The developed method has been successfully applied for analysis of target flame retardants in atmospheric PM2.5 collected from the cities of Guangzhou and Taiyuan, China. HFRs were found at concentrations of 45.7‒1230 pg m−3 and 51.2‒82.3 pg m−3 in Guangzhou and Taiyuan. The concentrations of HFRs were lower than those of OPFRs, which were detected at concentrations of 6004‒49,800 pg m−3 and 16,741‒34,346 pg m−3 in Guangzhou and Taiyuan. Accordingly, the analytical method is robust and useful for further elucidating the contamination profiles of flame retardants in PM2.5.

Under deep frying conditions, edible oil will release a variety of deterioration chemicals that have been implicated in many diseases. Unscrupulous traders may refine used cooking oil and adulterate it as qualified edible oil, thus posing threats to public health. This research aimed to discover the chemical markers of used cooking oil by using gas chromatography-mass spectrometry (GC-MS) based profiling. Our results suggested that six monoglycerides could be used as endogenous markers to discriminate used cooking oil from fresh edible oil. Accumulation behaviors of those markers in continuous heating process were observed. A quantitative GC-MS method was further developed for the six monoglycerides with good accuracy, precision and reproducibility. This method enabled the authentication of commercial olive oil adulterated with 1% deep fried oil. Abnormally high levels of the monoglycerides markers had also been determined in 116 gutter oil samples. Therefore, quantitation of six monoglycerides markers by GC-MS could be a promising approach for elucidating the degradation state of edible oil, authenticating commercial oil products adulterated with used cooking oil, as well as screening of gutter oil.

Short-chain chlorinated paraffins (SCCPs) were added to the Stockholm Convention on Persistent Organic Pollutants (POPs) at the eighth meeting of the conference of the parties in 2017. As a consequence, increasing environmental attention and international regulation on SCCPs is expected in the future. Inhalation uptake of particulate matter (PM) was an important exposure pathway for POPs into the human body. In the present study, a total of eighty PM2.5 samples were collected in the four seasons of the year at an urban site (Shandong University, Jinan) in Shandong province to investigate the seasonal changes of SCCPs and their inhalation exposure risks to human health. The concentrations of SCCPs ranged from 9.80 to 105 ng m−3, with the mean value of 38.7 ng m−3. The highest concentrations of SCCPs were detected in winter, while the lowest concentrations were in summer. SCCPs concentrations were positively correlated with the mass concentrations of PM2.5 (r = 0.629, p

Exposure to airborne fine particulate matter (PM2.5) is associated with various adverse effects. However, the molecular mechanism involved in PM2.5-elicited energy metabolic reprogramming and the toxic chemical determinants within PM2.5 are not well elucidated. In this study, nontargeted and targeted metabolomics research were conducted to investigate the overall metabolic changes and relevant toxicological pathways caused by Taiyuan winter total PM2.5 and its water soluble and organic soluble fractions in human lung bronchial epithelial cells (BEAS-2B). The results showed that significant metabolome alterations in BEAS-2B cells were observed after the exposure of total PM2.5 and its organic soluble fraction. Purine metabolism, arginine and proline metabolism, glutathione (GSH) metabolism, tricarboxylic acid (TCA) cycle and glycolysis were mainly affected. Along with a significant increase of reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), obvious metabolic phenotype remodeling from oxidative phosphorylation to glycolysis was found in BEAS-2B cells treated with total PM2.5 and its organic soluble fraction. Compared with water soluble fraction, organic soluble fraction was found to play the dominant role in PM2.5 toxicity. Our study provided novel insights into the mechanism of PM2.5-elicited toxicity.

In recent years, how to effectively remove emerging organic pollutants in water bodies has been studied extensively, especially in the actual complex water environment. In the present study, an effective wastewater treatment system that combined photocatalysis and an oxidizing agent was investigated. Specifically, visible-light driven reduced graphene oxide (RGO)/TiO2 composites were prepared, and peroxodisulfate (PDS) was used as electron acceptor to accelerate the photocatalytic activity of this material. The vis-RGO/TiO2/PDS system exhibited outstanding properties in the degradation of diclofenac (DCF), which was also facilitated by acidic conditions and Cl-. Lake water, tap water, river water and HCO3- decreased the DCF degradation rate, while NO3- affected the system only slightly. Low concentrations of fulvic acid (FA) promoted the degradation of DCF via the generation of excited states, whereas a high concentration of FA inhibited the degradation, which was likely due to the light screening effect. The photocatalytic mechanism revealed that PDS served as an electron acceptor for the promotion of electron-hole pair separation and the generation of additional reactive oxygen species, while the RGO served as an electric conductor. The active substances, h+, OH, 1O2, SO4- and O2- were generated in this system, O2- and h+ played significant roles in the degradation of DCF based electron spin resonance tests and radical quenching results. According to the mass spectrometry results, the amide bond cleavage, dechlorination reaction, hydroxyl addition reaction, and decarboxylation reaction were the primary transformative pathways.

Climbazole (CBZ) is an emerging contaminant with adverse effects on aquatic organisms. In this study, a floral array of chromium-substituted magnetite nanoparticles was synthesized, characterized, and used in photocatalytic degradation of CBZ. The results showed that Cr incorporation did not change the spinel structure of magnetite, but resulted in the obvious decrease of its crystallinity. The Cr content greatly influenced the morphology and micro-structure of magnetite nanoparticles, which led to a significantly larger surface area, and more abundant pores and surface hydroxyl groups. Factors such as the UV light source, catalyst concentration, initial level of CBZ, solution pH, peroxymonosulfate (PMS) dosage, and Cr level in magnetite affected the transformation of CBZ. Under the optimized photocatalytic conditions, i.e., 0.2 g L−1 Fe2.52Cr0.48O4, 2.0 μmol L−1 CBZ, 1.0 mmol L−1 PMS, and pH = 3.08, CBZ was almost completely eliminated within 30 min, which was much faster than under photodegradation, biodegradation, or chlorination reported previously. The reactive oxygen species including ˙OH and SO4˙− coexisted and participated in the photocatalytic reaction. The GC-MS analysis revealed the generation of 4-chlorophenol (4-CP) as a primary intermediate following CBZ transformation, based on the stoichiometric relationship between CBZ and 4-CP. The resultant 4-CP in the present study does not increase the risk to aquatic life. The results highlight an environmentally friendly strategy for effective elimination of CBZ.

An aqueous protocol was developed for nattokinase purification under scalable conditions using a combination of salting out, anion exchange chromatography and ultra-filtration. The enzyme was firstly washed off from the fermented soybeans. The whole proteins were precipitated by ammonium sulfate and purified by anion exchange chromatography. The purified enzyme was finally refined by size exclusion chromatography and ultra-filtration at laboratory and industry-compatible level, respectively. There was a 476.18-fold increase in enzymatic activity with a 48.3% yield at the laboratory level and 429.75-fold increase in enzymatic activity with a 42.7% yield at the industrial-compatible scale. The protocol was universally adaptive for purifying the fibrinolytic enzymes produced by bacillus tequilensis, bacillus amyloliquefaciens, and bacillus cereus, showing a purification efficiency of 329.76-fold with 42.7% yield, 221.78-fold with 32.5% yield, and 288.56-fold with 38.7% yield, respectively. All procedures are scalable, aqueous, simple, cost-effective, and suitable for fibrinolytic enzymes industrial production.

A magnetic covalent organic framework nanomaterial (Fe3O4@COFs) served as an adsorbent for enrichment and a new matrix for SALDI-TOF-MS analysis of PAHs and their derivatives in PM2.5. The unique properties of Fe3O4@COFs in terms of high enrichment ability and matrix-free interference made it possible for sensitive analysis of low-concentration organic small-molecule pollutants in complex environmental samples.

Type III-C rotaxane dendrimers were synthesized by a divergent approach. Dual shuttling behavior and size modulation were observed from non-methylated/methylated rotaxane dendrimers under the same external stimuli. The biological distribution of dendrimers in C57BL/6J mice determined by MALDI-TOF-MS shows predominant accumulation in the spleen and liver. Drug encapsulations with chlorambucil and lithocholic acid were demonstrated.

A rational strategy was introduced for the synthesis of a novel dual functionalized metal-organic framework nanocomposite (AuGC/ZIF-8) with ultra-hydrophilicity to enhance glycopeptide enrichment. The advantages of ingenious synergy, low-cost, facile and large-scale synthesis, and excellent enrichment performance will enable it to have a bright future in nanomaterial synthesis, glycoproteomics analysis, and related biochemistry.

We report a facile hydrothermal method to synthesize a novel mesoporous graphitic carbon nitride (MCN)@NiCo2O4 nanocomposite, which can be used as a solid phase microextraction coating for high efficiency extraction and preconcentration of trace polychlorinated biphenyls and polycyclic aromatic hydrocarbons in human serum samples.

Previous studies have proven the endocrine-disrupting properties and health hazards of parabens, triclosan, and benzophenones, but their relationship with blood pressure during pregnancy remains unknown. Therefore, we investigated the associations of repeated measures of urinary parabens, triclosan, and benzophenones with blood pressure during pregnancy and evaluated whether the associations were modified by fetal sex. From a prospective birth cohort in Wuhan, China, we collected urine samples from 644 pregnant women in the first, second, and third trimesters between 2014 and 2015. Five parabens, triclosan, and three benzophenones were quantified in all urine samples. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each trimester after urine sampling. Mixed linear models were used to estimate the associations between urinary chemical levels and blood pressure during pregnancy among all pregnant women and subgroups stratified by fetal sex. In the women carrying male fetuses, urinary triclosan and selected benzophenone concentrations were associated with a slight change of SBP during pregnancy. In the women carrying female fetuses, no chemical was associated with SBP, while urinary concentration of triclosan was inversely associated with DBP, though the magnitude was small. Urinary paraben levels weren't associated with blood pressure during pregnancy. Our results suggest that triclosan and selected benzophenone exposure might be associated with blood pressure during pregnancy in a potential fetal sex-different manner. Replicated research studies in pregnant women with higher triclosan and benzophenone exposure levels are needed in the future.

Perfluorooctane sulfonate (PFOS), an emerging environmental persistent pollutant, has attracted extensive attention due to its potential nephrotoxicity. However, little is known about the spatial variations of lipid metabolism associated with PFOS exposure. In this study, atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-MALDI MSI) was used to reveal the spatial distributions of PFOS and its adverse effect on lipid metabolism directly in mouse kidney sections. We have observed that PFOS accumulated in the renal pelvis and outer cortex regions, with some found in the medulla and inner cortex regions. Hematoxylin and eosin (HE) staining results also demonstrated that the accumulation of PFOS caused damage to the mouse kidney, which was consistent with AP-MALDI MSI results. Furthermore, a total of 42 lipids were shown to be significantly different in the spatial distribution patterns and variations between control and PFOS exposure mice groups, including the significant down-regulation of lyso-glycerophospholipids (Lyso-GPs), phosphatidic acids (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), phosphatidylserines (PS) sphingomyelins (SM) and sulfatides (ST) in renal medulla or cortex region of mouse kidney sections, and remarkable up-regulation of cholesterol and phosphatidylinositols (PI) in the cortex regions of mouse kidney sections. The AP-MALDI MSI provides a new tool to explore spatial distributions and variations of the endogenous metabolites for the risk assessment of environmental pollutants.

People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, which are environmental pollutants that may possess endocrine-disrupting potential; however, no epidemiological evidence is available on the associations of BTRs and BTHs with estrogens and androgens. This study aimed at investigating the associations of BTRs and BTHs with estrogens and androgens among pregnant women. Based on a prospective cohort study, we included 459 pregnant women who donated a complete serial of urine samples at each trimester and had repeated measurements of four BTRs, four BTHs, three estrogens (estrone, 17β-estradiol, and estrio), and two androgens (dehydroepiandrosterone and testosterone) in the urine samples. Associations of repeatedly measured BTRs and BTHs with maternal urinary estrogens and androgens were analyzed, and the cross-sectional associations were also analyzed. Tolyltriazole (TTR) (≥59.3%) and benzothiazole (BTH) (≥93.5%) had the highest detection rate among the BTRs and BTHs, respectively. Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with 17β-estradiol, estriol, and testosterone, while the trend of the associations with estrone and dehydroepiandrosterone was inconsistent. Among the positive associations with 17β-estradiol, estriol, and testosterone, the percent of change in estriol associated with TTR was the most prominent [28.5% (95% confidential interval: 24.2%, 32.9%) for each doubling in TTR]. The significant associations with estrone, estriol, testosterone, and dehydroepiandrosterone were stronger among pregnant women who gave birth to a boy than those who gave birth to a girl. These findings add epidemiological evidence on the endocrine-disrupting potential of BTRs and BTHs and highlight the importance of focusing on the health outcomes of BTRs and BTHs related to disturbed estrogens and androgens. Future studies are needed to validate these findings and explore the underlying mechanisms.

COVID-19 remains as a major threat to human society. A reliable, sensitive, rapid, and low requirement assay for serum neutralizing antibodies is needed as a pandemic management tool for estimation of revaccination time and implementation of "immune passport". Using gold nanoparticle (AuNR) as an immunosensor, we have established a semi-quantitative, instrument-free assay for measuring antibody level against SRAS-CoV-2 spike1 (S1) receptor binding domain (RBD) from fingertip blood samples. The testing results by the developed method correlated well with those obtained from conventional ELISA assay, indicating reliable quantitation could be achieved without use of plate reader. A declined of immunoglobulin G (IgG) antibody associated with vaccination time was observed, which agreed well with the data from other reports. The developed method provides a potentially complementary strategy for on-site measurement of COVID-19 antibodies.

Triclocarban (TCC) is considered an endocrine disruptor and shows antagonist activity on thyroid receptors. In view of the report that thyroid hormone signaling mediates retinal cone photoreceptor specification, we hypothesize that TCC could impair visual function, which is vital to wildlife. In order to verify our hypothesis, we assessed alteration in the retinal structure (retinal layer thickness and cell density), visually-mediated behavior, cone and rod opsin gene expression, and photoreceptor immunostaining in zebrafish larvae exposed to TCC at environmentally realistic concentrations (0.16 ± 0.005 µg/L, L-group) and one-fifth of the median lethal concentrations (25.4 ± 1.02 µg/L, H-group). Significant decrease in eye size, ganglion cell density, optokinetic response, and phototactic response can be observed in the L-group, while the thickness of outer nuclear layer, where the cell bodies of cone and rod cells are located, was significantly reduced with the down-regulation of critical opsin gene (opn1sw2, opn1mw1, opn1mw3, opn1lw1, opn1lw2, and rho) expression and rhodopsin immunofluorescence in the H-group. It should be noted that TCC could affect the sensitivity of zebrafish larvae to red and green light according to the results of behavioral and opsin gene expression analysis. These findings provide the first evidence to support our hypothesis that the visual system, a novel toxicological target, is affected by TCC. Consequently, we urgently call for a more in-depth exploration of TCC-induced ocular toxicity to aquatic organisms and even to humans.

Uncontrolled electronic-waste recycling processes have induced serious environmental pollution and human health impacts. This paper reviewed studies on the wide range of toxic chemicals through the use of primitive recycling techniques, their transfer to various ecological compartments, and subsequent health impacts. Results indicated that local food items were heavily polluted by the pollutants emitted, notably heavy metals in vegetables, rice, fish and seafood, and persistent organic pollutants (POPs) in livestock. Dietary exposure is the most important exposure pathway. The associations between exposure to e-waste and high body burdens of these pollutants were evident. It seems apparent that toxic chemicals emitted from e-waste activities are causing a number of major illnesses related to cardiovascular, digestive and respiratory systems, according to the information provided by a local hospital (Taizhou, an e-waste recycling hot spot in China). More epidemiological data should be made available to the general public. It is envisaged that there are potential dangers of toxic chemicals passing on to the next generation via placental transfer and lactation. There is a need to monitor the development and health impacts of infants and children, born and brought up in the e-waste sites.

RATIONALE Triclosan (TCS) and triclocarban (TCC) are ubiquitous antimicrobial agents incorporated in consumer and personal care products. Due to their human health risks, it is essential to develop a sensitive and accurate analytical method to simultaneously quantify TCS, TCC, as well as their metabolites and byproducts in urine and serum samples. METHODS The quantitative parameters of TCS, TCC, TCC metabolites and byproducts (2'-OH-TCC, 3'-OH-TCC, 6-OH-TCC, DHC, DCC, NCC) were optimized by using ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC/ESI-MS/MS). Enzymatic hydrolysis of the samples was optimized based on enzyme dosage and incubation time. The efficiencies of solid-phase extraction (SPE) and liquid-liquid extraction (LLE) were compared. The effectiveness of the established method was evaluated, and method application was validated using real urine and serum samples. RESULTS The conjugates were sufficiently hydrolyzed under 500 U/mL β-glucuronidase and 80 U/mL sulfatase at 37°C for 4 h. Compared with the LLE method, SPE achieved higher extraction efficiency in both urine and serum samples. The optimized SPE-UHPLC/ESI-MS/MS method showed low limits of detection (LODs) in the range 0.001-0.3 ng/mL and good linearity (R2 > 0.99) at 0.01-150 ng/mL in both matrices. Excellent recoveries of 82.0%-120.7% (urine) and 76.7%-113.9% (serum) were obtained with low relative standard deviation (RSD

Using MIL-101(Fe) as the source of carbon and Fe, a magnetic porous carbon (MPC) material with Fe3C nanoparticles encapsulated in porous carbon was prepared through one-pot pyrolysis under N2 atmosphere. With MPC as adsorption material, a stir bar sorptive-dispersive microextraction (SBSDME) method was proposed to extract and preconcentrate sulfonamides (SAs) prior to HPLC-DAD determination. To investigate their extraction ability, different MPC materials were prepared under different carbonization temperatures (600, 700, 800, 900, and 1000 °C). The material prepared under 900 °C (MPC-900) exhibited the highest extraction ability for SAs. The as-prepared MPC materials were also characterized by Raman spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, zeta potential, and other techniques. The main parameters that affect extraction were systematically studied. Under optimal conditions, favorable linearity (R2 ≥ 0.9938) and detection limits (0.02–0.04 ng mL−1) of sulfonamides were obtained. The average recoveries for spiked milk and lake water samples ranged from 76.9 to 109% and from 75.4 to 118% with RSDs of 3.10–9.63% and 1.71–11.3%, respectively. Sulfameter and sulfisoxazole were detected in milk sample. Sulfisoxazole was detected in the lake water sample. The MPC-900 material demonstrated excellent reusability. It can be reused 24 times with peak areas having no obvious decline. The method can be applied to extract ultra-trace compounds in complex sample matrices.

N6-methyladenosine (mYTH N6-methyladenosine RNA binding protein 1 (Ythdf1) knockout mouse was generated to determine the effect of Ythdf1 in CRC tumorigenesis in vivo. Multiomic analysis of RNA-sequencing, mDNA copy number gain of YTHDF1 is a frequent event in CRC and contributes to its overexpression. High expression of YTHDF1 is significantly associated with metastatic gene signature in patient tumors. Ythdf1 knockout in mice dampened tumor growth in an inflammatory CRC model. YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. Integrative multiomics analysis identified RhoA activator ARHGEF2 as a key downstream target of YTHDF1. YTHDF1 binds to mWe identify a novel oncogenic epitranscriptome axis of YTHDF1-m

Three-dimensional (3D) multicellular tumor spheroids (MCTS) that mimic the complex tumor microenvironment provide a good platform for in vitro study of drug and endogenous metabolites. Hydroxychloroquine (HCQ) has shown anti-tumor activity in a variety of tumor models. However, the effect of the drug on the alteration of lipid metabolism spatial composition and distribution in the MCTS model is not clear. Herein, we utilized matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in the analysis of A549 lung cancer multicellular spheroids to investigate the in situ spatial distribution of HCQ and its effect on lipid metabolism. We have successfully observed the spatial variations of HCQ in the inner region of the spheroid at different drug-treated time points. The MSI results also demonstrated that HCQ treatment altered the spatial composition of lipids in the inner and outer regions of treated spheroids. Furthermore, the lipidomic results showed that the identified phosphatidylcholines (PC), lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), lysophosphatidylethanolamines (LPE), phosphatidylinositols (PI), ceramides (Cer), glucosylceramides (CerG), and diglycerides (DG) were significantly up-regulated, and phosphatidylglycerol (PG) and triglycerides (TG) were remarkable down-regulated. MSI method combined with LC-MS/MS profiling of endogenous metabolites can obtain more detailed information about how spheroids respond to drug and spatial distribution information, thus fostering a better understanding of the relationship between drug-altered lipid metabolism and cancer microenvironment.

Natural polysaccharide as the third abundant biomacromolecule has attracted considerable attentions due to their superior anti-tumor activities. However, the anti-tumor mechanism of polysaccharides has not been completely understood. Herein, the anti-tumor effects of black fungus polysaccharide (BFP), a typical β-glucan was comprehensively investigated, and the anti-tumor mechanism was obtained from metabolomics profiling. The in vitro results demonstrate that BFP inhibited the proliferation, migration and invasion of hepatoma carcinoma cells (HCC) through inducing the cell apoptosis and arresting the cell cycle at S phase without direct cytotoxicity. The hepatoma-bearing nude mice experiments further demonstrate that BFP could significantly inhibit the growth without system toxicity in vivo. Mass spectrometry-based metabolomics unveils that BFP significantly disturbed the multiple metabolic pathways, leading to the inhibition of tumor cells proliferation by promoting DNA damage, attenuating DNA damage repair, and inhibiting DNA synthesis. This study provides new insights for pharmacological research and clinical practice of polysaccharides.

Fine particulate matter (PM2.5) samples collected in 2018 in Taiyuan, a typical industrial and mining city in North China Plain (NCP), were characterized based on ultrahigh-performance liquid chromatography (UHPLC) coupled with orbitrap mass spectrometry. Potential molecular identifications based on precise molecular weight were conducted to obtain the compositional and source information of organic aerosols (OAs) in this city. Evident variation trends were observed during the sampling period in the composition, degree of oxidation and saturation of the obtained molecules. The proportion of CHOS- and CHO+ were increased from winter to summer and then decreased, conversely the proportion of CHN+ was decreased from winter to summer and then increased. By reclassifying the molecules, OA molecules were observed to be more saturated and oxidized in summer. It was caused by the high abundance of organosulfates (OSs) in summer, and aromatic amines/N-heterocycle aromatic hydrocarbons (PANHs) in winter. Molecular identification indicated that the OSs were basically originated from biogenic source isoprene or monoterpene, while the aromatic amines and PANHs were related to anthropogenic emissions of fossil fuel combustion, like other cities in the NCP area. The prevailing northwesterlies in winter may bring coal-burning pollutants from other cities, while the high abundance of organosulfates in summer may be related to the PM2.5 transportation from Shijiazhuang. This study firstly demonstrates the molecular composition characteristics, potential sources, and geographical origins of PM2.5 in Taiyuan, which gives a comprehensive understanding of PM2.5 in a typical industrial and mining city.

Significance Some RNAs in both prokaryotes and eukaryotes were recently found to contain the NAD+ cap, indicating a novel mechanism in gene regulation through noncanonical RNA capping. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry has been used to label NAD+-capped RNAs (NAD-RNAs) for their identification. However, copper-caused RNA fragmentation/degradation interferes with the analysis. We developed the NAD tagSeq II method for transcriptome-wide NAD-RNA analysis based on copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. This method was used to compare NAD-RNA and total transcriptome profiles in Escherichia coli. Our study reveals genome-wide alterations in E. coli RNA NAD+ capping in different growth phases and indicates that NAD-RNAs could be the primary form of transcripts from some genes under certain environments., Recent findings regarding nicotinamide adenine dinucleotide (NAD+)-capped RNAs (NAD-RNAs) indicate that prokaryotes and eukaryotes employ noncanonical RNA capping to regulate gene expression. Two methods for transcriptome-wide analysis of NAD-RNAs, NAD captureSeq and NAD tagSeq, are based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry to label NAD-RNAs. However, copper ions can fragment/degrade RNA, interfering with the analyses. Here we report development of NAD tagSeq II, which uses copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) for labeling NAD-RNAs, followed by identification of tagged RNA by single-molecule direct RNA sequencing. We used this method to compare NAD-RNA and total transcript profiles of Escherichia coli cells in the exponential and stationary phases. We identified hundreds of NAD-RNA species in E. coli and revealed genome-wide alterations of NAD-RNA profiles in the different growth phases. Although no or few NAD-RNAs were detected from some of the most highly expressed genes, the transcripts of some genes were found to be primarily NAD-RNAs. Our study suggests that NAD-RNAs play roles in linking nutrient cues with gene regulation in E. coli.

Pollutant-attached microplastics have received increasing attention in recent years. However, information regarding the influence of hydroxyl group content of pollutants on the adsorption and desorption behavior is unclear, which affects their fate and risks in the aquatic environment. In this study, we investigated the adsorption and desorption behavior of anthracene (ANT) and its hydroxy derivatives (OHAs), including 2-hydroxyanthracene (MOHA), 2,6-dihydroxyanthracene (DOHA), and 1,8,9-trihydroxyanthracene (TOHA) on polyvinyl chloride (PVC) microplastics, and their interaction mechanism through the batch, characterization, and computational experiments. The results showed that the adsorption of ANT and OHAs on PVC microplastics conformed to the pseudo-second-order kinetic model and was exothermic spontaneously. The adsorption efficiency on PVC followed the order of ANT > MOHA > DOHA > TOHA, indicating that increase in hydroxyl group substitution degree will inhibit pollutant adsorption on PVC microplastics. Conversely, the release amounts of MOHA from PVC into simulated gastric fluids were higher than those of ANT. Experimental and computational results suggested that the affinity of ANT/OHAs to PVC microplastics was the most likely outcome in hydrophobic effect, electrostatic repulsion, and CH-π interaction forces. These findings help elucidate the mechanisms of pollutant adsorption on microplastics and evaluate the risk of pollutant-attached microplastics in the aquatic environment.

Perfluorohexanoic acid (PFHxA), one of the short-chain perfluoroalkyl acids (PFAAs), is considered as a substitute of perfluorooctane sulfonate (PFOS). This emerging organic pollutant is persistent and highly bioavailable to humans, raising concerns about its potential health risks. There are currently few researches on the toxicity of PFHxA. Liver has been suggested to be the main target of PFHxA toxicity, and the mechanism remains unclear. Herein, we investigated the transcriptomic, proteomic, and metabolomic landscape in PFHxA-exposed mice. Using these approaches, we identified several valuable biological processes involved in the process of liver injury, comprising fatty acid biosynthesis and degradation pathways, which might be induced by peroxisome proliferator-activated receptor (PPAR) signaling pathway. These processes further promoted oxidative stress and induced liver injury. Meanwhile, abnormalities in purine metabolism and glutathione metabolism were observed during the liver injury induced by PFHxA, indicating the production of oxidative stress. Finally, our present multi-omics studies provided new insights into the mechanisms involved in PFHxA-induced liver injury.

Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

Humans are constantly exposed to antimicrobial triclocarban (TCC) via direct skin contact with personal care and consumer products, but the safety of long-term dermal exposure to TCC remains largely unknown. Herein, we used a mouse model to evaluate the potential health risks from the continuous dermal application of TCC at human-relevant concentrations. After percutaneous absorption, TCC circulated in the bloodstream and largely entered the liver-gut axis for metabolic disposition. Nontargeted metabolomics approach revealed that TCC exposure perturbed mouse liver homeostasis, as evidenced by the increased oxidative stress and impaired methylation capacity, leading to oxidative damage and enhancement of upstream glycolysis and folate-dependent one-carbon metabolism. Meanwhile, TCC was transformed in the liver through hydroxylation, dechlorination, methylation, glucuronidation, sulfation, and glutathione conjugation. TCC-derived xenobiotics were subsequently excreted into the gut, and glucuronide and sulfate metabolites could be further deconjugated by the gut microbiota into their active free forms. In addition, microbial community analysis showed that the composition of gut microbiome was altered in response to TCC exposure, indicating the perturbation of gut homeostasis. Together, through tracking the xenobiotic-biological interactions in vivo, this study provides novel insights into the underlying impacts of dermally absorbed TCC on the liver and gut microenvironments.

Fine particulate matter (PM

Background The association between exposure to organochlorine pesticides (OCPs) and infant growth has been reported contradictorily in previous studies. Few studies have investigated the effects of prenatal exposure to OCPs on infant growth assessed longitudinally at multiple time points. Objectives The purpose of the study was to examine the associations between prenatal exposure to OCPs and infant growth at birth, 6, 12 and 24 months of age, and further to explore the potential sex-specific effects. Methods The study population included 1039 mother-infant pairs who participated in a birth cohort study in Wuhan, China. The weight, length and body mass index (BMI) z-score of infants were measured and calculated at birth, 6, 12 and 24 months of age. The overweight status was defined as BMI z-score ≥ 85th percentile according to the standard of World Health Organization. The concentrations of OCPs were measured in cord serum, including hexachlorocyclohexanes (HCHs, consisted of α-HCH, β-HCH, and γ-HCH), p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) and its metabolites: p,p′-dichlorodiphenyldichloroethane (p,p′-DDD), and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE). Generalized linear models were applied to estimate the associations of cord OCPs with infant growth parameters. A group-based semiparametric mixture model was used to estimate growth patterns of infants. Linear-mixed growth curve models were used to examine relationships between predicted growth trajectories and prenatal exposure to OCPs. Weighted quantile sum regression (WQSR) analyses were used to estimate the mixture effects of OCPs on infant growth. Results Higher cord serum β-HCH concentrations were associated with higher BMI z-score at 12 [β = 0.07, 95%CI: 0.01, 0.13] and 24 months of age [β = 0.08, 95% CI: 0.02, 0.14]. Similar patterns were observed for relationships of γ-HCH [β = 0.04, 95%CI: 0.01, 0.07] and p,p′-DDT [β = 0.03, 95% CI: 0.00, 0.06] with BMI z-score at 6 and 12 months of age, respectively. However, higher cord serum p,p′-DDE concentrations were associated with a reduction of BMI z-score at 6 months of age [β = −0.07, 95% CI: −0.12, −0.01]. Cord serum β-HCH was also positively associated with the risk of overweight at 12 months of age [RR = 1.16, 95% CI (1.02, 1.33), for the medium vs the lowest tertile]. Among girls, the effects of β-HCH on BMI z-score and overweight status were stronger than boys at 12 and 24 months of age. No statistically significant relationships of other OCPs with infant growth were observed. Conclusions Prenatal exposure to β-HCH was associated with increased BMI z-score and higher risk of overweight status in infants especially at 12 and 24 months of age, which seemed to be stronger in girls.

Magnetic covalent organic frameworks (Fe3O4@TPPCl4) were synthesized via a one-pot process in which magnetic nanoparticles (Fe3O4@MNP) served as a magnetic core and 2,4,6-trihydroxy-1,3,5-benzenetricarbaldehyde (TP) and 2,2′,5,5′-tetrachlorobenzidine (PCl4) as two building blocks to form a shell. The as-prepared Fe3O4@TPPCl4 nanoparticles have superior features, including large surface area (186.5 m2 g−1), high porosity, strong magnetic responsiveness (42.6 emu g−1), high chlorine content, and outstanding thermal stability, which make them an ideal adsorbent for highly selective enrichment of polychlorinated naphthalenes (PCNs). Combining with atmospheric pressure gas chromatography tandem mass spectrometry (APGC-MS/MS), a simple analytical method of Fe3O4@TPPCl4-based magnetic solid-phase extraction (MSPE)-APGC-MS/MS was developed, which exhibited good linearity (r ≥ 0.9991) for eight PCNs in the concentration range 0.1–100 ng L−1. Moreover, low detection limits (0.005–0.325 ng L−1), high enrichment factors (46.62–81.97-fold), and good relative standard deviations (RSDs) of inter-day (n = 3, 1.64 to 7.44%) and day-to-day (n = 3, 2.62 to 8.23%) were achieved. This method was successfully applied to the selective enrichment of PCNs in fine particulate matter (PM)2.5 samples, and ultra-trace PCNs were found in the range 1.56–3.75 ng kg−1 with satisfactory recoveries (93.11–105.81%). The successful application demonstrated the great potential of Fe3O4@TPPCl4 nanoparticles as an adsorbent for enrichment of halogenated compounds.

Summary: The liver plays central roles in coordinating different metabolic processes, such as the catabolism of amino acids. In this study, we identify a loss of tyrosine catabolism and a concomitant increase in serum tyrosine levels during liver cancer development. Liver cells with disordered tyrosine catabolism, as exemplified by the suppression of a tyrosine catabolic enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), display augmented tumorigenic and proliferative potentials. Metabolomics profiling and isotope tracing reveal the metabolic reliance of HPD-silenced cells on glutamine, coupled with increased tricarboxylic acid cycle metabolites and their associated amino acid pools. Mechanistically, HPD silencing reduces ketone bodies, which regulate the proliferative and metabolic phenotypes via the AMPK/mTOR/p70S6 kinase pathway and mTOR-dependent glutaminase (GLS) activation. Collectively, our results demonstrate a metabolic link between tyrosine and glutamine metabolism, which could be exploited as a potentially promising anticancer therapy for liver cancer.

Ambient air fine particulate matter (PM

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 μM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 μM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 μM and 100 μM). Remarkably, global metabolomics results displayed that 10 μM PFOA exposure affected glutamine related pathways and the exposure at 100 μM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 μM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.

Cadmium is a well-known hazardous pollutant that mainly comes from dietary, tobacco and occupational exposure, posing threat to kidney. However, there is still a lack of systematic study on metabolic pathways and urinary biomarkers related to its nephrotoxicity under cadmium exposure for both females and males. In this study, a mass spectrometry-based metabolomics investigation of a cohort of 144 volunteers was conducted to explore sex-specific metabolic alteration and to screen biomarkers related to cadmium-induced nephrotoxicity. When the concentration of urinary cadmium increased, creatine pathway, amino acid metabolism especially the tryptophan metabolism, aminoacyl-tRNA biosynthesis, and purine metabolism were primarily influenced regardless of the gender. Also, the most specific biomarkers linked with nephrotoxicity based on the statistical analysis were detected including creatine, creatinine, l-tryptophan, adenine and uric acid. The study outcome might provide information to reflect the body burden and help improve health policy for risk assessment.