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Rope saw technology played an important role in the field of high hardness material processing due to the high cutting efficiency, low equipment costs, energy saving and environmental protection. However, traditional wire saws can often become too slack for the beaded rope to cut due to reduced tension during the cutting process. A new diamond bead rope adaptive adjustment cutting method is proposed based on the conventional wire saw. Firstly, the three-dimensional structure of the beaded rope self-adjusting wire saw is modeled by SOLIDWORKS. Secondly, the modal analysis of the beaded rope adaptive adjustment wire saw is proposed based on the ANSYS. Thirdly, the kinematic model is established, and the dynamics of adaptive adjustment mechanism of diamond beaded rope wire saw is analyzed and verified by ADAMS. Finally, the mechanical property of the adaptive adjustment mechanism is analyzed by ADAMS and MATLAB co-simulation. The mechanical structure of the diamond wire saw is innovatively designed and its advantages are verified through dynamic analysis and co-simulation. This research provides reference value for the optimization research of wire saw machine in the future.

BACKGROUND Selenium (Se)-enriched glycoproteins have been a research highlight for the role of both Se and glycoproteins in immunoregulation. Arsenic (As) is a toxicant that is potentially toxic to the immune function and consequently to human health. Several reports suggested that Se could reduce the toxicity of heavy metals. Moreover, more and more nutrients in food had been applied to relieve As-induced toxicity. Hence glycoproteins were isolated and purified from Se-enriched Grifola frondosa, and their preliminary characteristics as well as amelioration effect and mechanism on As3+ -induced immune toxicity were evaluated. RESULTS Four factions, namely Se-GPr11 (electrophoresis analysis exhibited one band: 14.32 kDa), Se-GPr22 (two bands: 20.57 and 31.12 kDa), Se-GPr33 (three bands: 15.08, 20.57 and 32.78 kDa) and Se-GPr44 (three bands: 16.73, 32.78 and 42.46 kDa), were obtained from Se-enriched G. frondosa via DEAE-52 and Sephacryl S-400 column. In addition, Se-GPr11 and Se-GPr44 are ideal proteins that contain high amounts of almost all essential amino acids. Thereafter, the RAW264.7 macrophage model was adopted to estimate the effect of Se-GPr11 and Se-GPr44 on As3+ -induced immune toxicity. The results showed that the pre-intervention method was the best consequent and the potential mechanisms were, first, by improving the oxidative stress state (enhancing the activity of superoxide dismutase and glutathione peroxidase, decreasing the levels of reactive oxygen species and malondialdehyde); secondly, through nuclear factor-κB and mitogen-activated protein kinase-mediated upregulation cytokines (interleukin-2 and interferon-γ) secretion induced by As3+ . CONCLUSION The results suggested Se-enriched G. frondosa may be a feasible supplement to improve health level of the As3+ pollution population. © 2021 Society of Chemical Industry.

Endocrine-disrupting chemicals (EDCs) are now ubiquitously distributed in the environment. Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) pollution in environment media poses a significant threat to humans and aquatic organisms as a result of its potential neurotoxicity and endocrine-disrupting effect. The endocrine-disrupting effects of TBBPA-DHEE on aquatic organisms, however, have received limited attention. In this study, the neurotoxicity and reproductive endocrine-disruptive effect of TBBPA-DHEE was evaluated by observing the neurobehavioral changes, vitellogenin (VTG), testosterone, 17β-estradiol and gene expression levels in adult male and female zebrafish exposed to TBBPA-DHEE (0.05, 0.2 and 0.3 mg/L) for 100 days. Furthermore, transcriptomic analysis was conducted to unravel other potential neuroendocrine-disrupting mechanism. Our result showed TBBPA-DHEE significantly (p 0.05) altered the locomotor behavior and motor coordination abilities in both sexes. Steroid hormone and VTG levels were also altered indicating the neuroendocrine-disrupting effect of TBBPA-DHEE on the hypothalamic-pituitary-gonadal-axis. A total of 1568 genes were upregulated and 542 genes downregulated in males, whereas, 1265 upregulated and 535 downregulated genes were observed in females. The KEGG enrichment analysis showed that cell cycle and p55 signaling pathways were significantly enriched due to TBBPA-DHEE exposure. These pathways and its component genes are potential target of EDCs. The significant upregulation of genes in these pathways could partly explain the neuroendocrine disrupting effect of TBBPA-DHEE. The observed toxic effects of TBBPA-DHEE observed in this study is confirmation of the endocrine-disrupting toxicity of this chemical which would be valuable in biosafety evaluation and biomonitoring of TBBPA-DHEE for public health purposes.

TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE) pollution in the environment has raised serious public health concerns due to its potential neuroendocrine-disrupting effects. The neuroendocrine-disrupting effects of TBBPA-DHEE on marine spices, on the other hand, have received little attention. The behavioral, neuroendocrine-disrupting, and possible reproductive toxicity of TBBPA-DHEE were assessed in sexual developing zebrafish treated for 40 days by examining locomotor activity, Gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, and quantifying gene expression. In addition, transcriptome profiling was carried out to explore the possible mechanisms. According to our findings, TBBPA-DHEE treated zebrafish showed altered locomotor activity, a potential neuroendocrine-disrupting effect via the toxic effect on the hypothalamus and pituitary gland, which is evident in decreased levels of GnRH, FSH, and LH, according to our findings. The transcriptomic profiling reveals that a total of 216 DEGs were detected (5 upregulated and 211 down-regulated). Transcriptomic analysis shows that TBBPA-DHEE exposure caused decreased transcript levels of genes (cyp11a1, ccna1, ccnb2, ccnb1, cpeb1b, wee2) involved in cell cycle oocyte meiosis, progesterone mediated oocyte maturation, and ovarian steroidogenesis, which are known reproduction-related pathways. Overall, these findings add to our understanding of the impact of TBBPA-DHEE and biomonitoring in the maritime environment.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance (IR) and has attracted worldwide attention due to its high prevalence. As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) has been detected in food and human samples, and the concentration trends increase year by year. In addition, it has been proved to have the potential to increase the risk of IR, but it is rarely reported whether it could aggravate IR in T2DM. Therefore, in this study, the IR-BRL (buffalo rat liver cells with IR) model was applied to study the metabolism toxicity and susceptibility of BDE-209. Results showed that BDE-209 could inhibit glucose absorption and increase the levels of serum total cholesterol (TC) and triglyceride (TG), ultimately leading to the disorder of glucolipid metabolism in IR-BRL cells. Besides, it also could cause cell damage by increasing the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in cells. Moreover, its potential mechanisms were to: (1) affect the transport of glucose, synthesis of glycogen and fatty acid via IRS-1/GLUT4 and IRS-1/PI3K/AKT/GSK-3β pathways; (2) impact the proliferation and differentiation by regulating the expression of Mek1/2, Erk1/2, and mTOR proteins and genes. Furthermore, susceptibility analysis showed that there was a significant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.

A variety of beneficial pharmacological activities have been reported for Se-enriched Grifola frondosa polysaccharides. However, little has been reported on its absorption, and its intestinal uptake and transport profiles remain unknown. Based on our previous research, the aim of this study was to investigate its absorption from two aspects - the polysaccharides and selenium of Se-enriched Grifola frondosa polysaccharides (Se-GFP-22) across Caco-2 cells in vitro. The Caco-2 cells monolayer culture model was successfully constructed to study the transport and uptake of Se-GFP-22. The results revealed that the uptake and transport of Se-GFP-22 were time- and concentration- dependent. Transport studies illustrated that Se-GFP-22 could penetrate Caco-2 cells, mainly mediated through the same routes as endocytosis and selenium in the organic selenium (Se-GFP-22) was more easily absorbed than that in the inorganic selenium control group (sodium selenite). The uptake of Se-GFP-22 may be a macropinocytosis pathway, which was an accumulation from cytoplasm to nucleus process. Se-GFP-22 was a moderately absorbed biological macromolecule testified by the apparent permeability coefficients (Papp) value and transport rates. This work illustrates the characteristics on uptake and transport of Se-GFP-22 and all these results may help to explore the mechanism of polysaccharide absorption in vitro.

Abelmoschus esculentus L (okra) is widely used as a healthy vegetable and favourable source of dietary medicine. Okra flowers which are by-products of okra, are rich in polysaccharide, polyphenols and trace elements etc., however, except a few for health tea, most of them were discarded as the waste of resources. In this study, a polysaccharide named AEFP22 was extracted, purified and identified from okra flowers, and its physicochemical property and antioxidant activity were also elucidated. AEFP22, with a molecular weight of 2.741 × 105 Da, was composed of Rha, GalA and Gal in the ratio of 1: 1.02: 0.86. The methylation and nuclear magnetic resonance (NMR) analysis indicated AEFP22 was composed of [2)-α-D-Rhap-(1 → 4)-α-D-GalpA-(1 → 2,4)-α-D-Rhap-(1 → 4)-α-D-GalpA-(1] with branch of terminal T-α-D-Galp pointed at C4 of 1,2,4-α-D-Rhap. The Conge-red test, Atomic force microscope (AFM) and Scanning electron microscope (SEM) further revealed the triple-helical conformation, irregular sheet structure with molecule aggregations of AEFP22. The physicochemical property analysis indicated AEFP22 possessed stable thermal property and exhibited shear-thinning and normal Newtonian fluid in different concentrations, −7.04 mV zeta potential and polymerization phenomenon existed in AEFP22 solution. AEFP22 exhibited good 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability. These results indicated potential utilization of AEFP22 in nutritional food and material application.

In the present study, the neurotoxicity and mechanisms of di-(2-ethylhexyl) phthalate (DEHP) exposure on pubertal normal (P-normal) and pubertal type 2 diabetes mellitus (P-T2DM) mice were investigated by typical neurobehavioral methods and transcriptome analysis. Pubertal male ICR mice were orally exposed to DEHP (0.18, 1.8, 18 and 180 mg/kg/d) for 3 weeks. In Open field test, DEHP significantly increased the time in central area staying and decreased the total distance and clockwise (CW) rotation of P-normal and P-T2DM mice. Morris water maze showed that DEHP significantly increased the latency in locating platform and decreased the original platform quadrant and residence time in target quadrant of P-normal and P-T2DM mice. Transcriptome analysis results revealed the effects of DEHP exposure on neural signaling pathway including biogenic amines neurotransmitters, nerve receptors, neurobiological processes, etc. Enzyme-linked immunosorbent assay (ELISA) and western blotting results showed that DEHP significantly decreased the contents of 5-HT, cAMP, GABA and Ca2+, the levels of CREB, phosphorylation of PKA, ERK1/2 and CREB, increased the levels of CaM and phosphorylation of CaMKII in P-normal and P-T2DM mice. Factorial analysis results showed that P-T2DM mice were more sensitive than those of P-normal mice. The potential neurotoxicity mechanism of DEHP may be synergistically mediated by the cAMP-PKA-ERK1/2-CREB signaling and the Ca2+ signaling pathway.

In this study, the immature mice were taken to assess the potential neurological toxicity of lead (Pb) and di (n-butyl) phthalates (DBP) combination exposure. Mouse administration with DBP combination with Pb exhibited longer escape latency and lower average number of crossing of the platform. Pb content in the tissues was increased, especially in the brain, after Pb exposure as compared to those without Pb exposure. The alterations of oxidative damages in tissues (MDA and SOD) and biochemical indicators in the brain (AChE, TNOS, and iNOS) were observed, as well as the synergistic effect of joint exposure. Expressions of apoptosis-related protein (bax/bcl-2 ratio and caspase-3) were significantly increased in the hippocampus, while the bcl-2 was remarkably decreased and no significant differences were observed on the bax. The results suggested that the possible mechanisms for the learning and memory ability impairments were as follows: Firstly, the combination exposure induced the occurrence of lipid peroxidation in the brain, leading to damage to the brain cells. Secondly, it destroyed the normal metabolic balance of ACh, causing nerve damage in mice. Thirdly, it induced apoptosis in mouse hippocampal cells. The overall findings revealed that Pb and DBP co-exposure greatly influenced the developmental nervous system and accompanied with synergistic toxic effect.

TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of the main derivatives of TBBPA, has been widely detected in environmental samples and been discovered to be potential neurotoxic. In this study, the juvenile zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure, and to reveal the neurotoxicity susceptibility in different sexes. Behavioral studies revealed that TBBPA-DHEE could significantly reduce the swimming velocity, maximum acceleration and cumulative duration of high-speed mobility, significantly increasing the cumulative duration of low-speed mobility and average social distance. It significantly reduced the contents of ATP, glutamate and Ca

Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.

Marine oil spills emanating from wells, pipelines, freighters, tankers, and storage facilities draw public attention and necessitate quick and environmentally friendly response measures. It is sometimes feasible to contain the oil with booms and collect it with skimmers or burn it, but this is impracticable in many circumstances, and all that can be done without causing further environmental damage is adopting natural attenuation, particularly through microbial biodegradation. Biodegradation can be aided by carefully supplying biologically accessible nitrogen and phosphorus to alleviate some of the microbial growth constraints at the shoreline. This review discussed the characteristics of oil spills, origin, ecotoxicology, health impact of marine oils spills, and responses, including the variety of remedies and responses to oil spills using biological techniques. The different bioremediation and bio-dispersant treatment technologies are then described, with a focus on the use of green surfactants and their advances, benefits/drawbacks. These technologies were thoroughly explained, with a timeline of research and recent studies. Finally, the hurdles that persist as a result of spills are explored, as well as the measures that must be taken and the potential for the development of existing treatment technologies, all of which must be linked to the application of integrated procedures.

Nanotechnology is a rapidly developing technology that will have a significant impact on product development in the next few years. The technology is already being employed in cutting-edge cosmetic and healthcare products. Nanotechnology and nanoparticles have a strong potential for product and process innovation in the food industrial sector. This is already being demonstrated by food product availability made using nanotechnology. Nanotechnologies will have an impact on food security, packaging materials, delivery systems, bioavailability, and new disease detection materials in the food production chain, contributing to the UN Millennium Development Goals targets. Food products using nanoparticles are already gaining traction into the market, with an emphasis on online sales. This means that pre- and post-marketing regulatory frameworks and risk assessments must meet certain standards. There are potential advantages of nanotechnologies for agriculture, consumers and the food industry at large as they are with other new and growing technologies. However, little is understood about the safety implications of applying nanotechnologies to agriculture and incorporating nanoparticles into food. As a result, policymakers and scientists must move quickly, as regulatory systems appear to require change, and scientists should contribute to these adaptations. Their combined efforts should make it easier to reduce health and environmental impacts while also promoting the economic growth of nanotechnologies in the food supply chain. This review highlighted the benefits of a number of nano enabled agrochemicals/materials, the potential health impacts as well as the risk assessment and risk management for nanoparticles in the agriculture and food production chain.

BFRs (brominated flame retardants) are a class of compounds that are added to or applied to polymeric materials to avoid or reduce the spread of fire. Tetrabromobisphenol A (TBBPA) is one of the known BFR used many in industries today. Due to its wide application as an additive flame retardant in commodities, TBBPA has become a common indoor contaminant. Recent researches have raised concerns about the possible hazardous effect of exposure to TBBPA and its derivatives in humans and wildlife. This review gives a thorough assessment of the literature on TBBPA and its derivatives, as well as environmental levels and human exposure. Several analytical techniques/methods have been developed for sensitive and accurate analysis of TBBPA and its derivatives in different compartments. These chemicals have been detected in practically every environmental compartment globally, making them a ubiquitous pollutant. TBBPA may be subject to adsorption, biological degradation or photolysis, photolysis after being released into the environment. Treatment of TBBPA-containing waste, as well as manufacturing and usage regulations, can limit the release of these chemicals to the environment and the health hazards associated with its exposure. Several methods have been successfully employed for the treatment of TBBPA including but not limited to adsorption, ozonation, oxidation and anaerobic degradation. Previous studies have shown that TBBPA and its derivative cause a lot of toxic effects. Diet and dust ingestion and have been identified as the main routes of TBBPA exposure in the general population, according to human exposure studies. Toddlers are more vulnerable than adults to be exposed to indoor dust through inadvertent ingestion. Furthermore, TBBP-A exposure can occur during pregnancy and through breast milk. This review will go a long way in closing up the knowledge gap on the silent and over ignored deadly effects of TBBPA and its derivatives and their attendant consequences.

In this work, novel Cu-Co bimetal/reduce graphene oxide nanostructures with excellent catalytic activity were prepared by embedding Cu-Co bimetallic nanospheres into the interlayer of graphene. The composite materials were characterised by X-ray diffraction (XRD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) etc. The characterisation results indicated that the diameters of the bimetallic nanospheres were controlled within ~60 nm, which embedded uniformly in graphene. A series of electrochemical tests were carried out and the composites were found to exhibit excellent oxygen evolution properties under alkaline conditions. The excellent catalytic activity and stability make the composite have great potential for wide application and provide a basis for its industrial application.

Subcritical water extraction (SWE) of bioactive extracts from Radix Puerariae (RP) was firstly optimized by response surface methodology (RSM) and its extraction efficiency was compared with two traditional volatile isolation methods including hot water extraction (HWE) and ethanol reflux extraction (ERE). The optimal SWE parameters were as follows: extraction temperature of 141 °C, extraction time of 58 min, and liquid-solid ratio l of 23:1 mL/g. Under these conditions, yield of bioactive extracts was 28.9 ± 0.2%, which was slightly higher than that obtained by ERE, and more than two-fold the value obtained by HWE respectively. Isoflavones and polysaccharide content in SWE was significantly higher than that of HWE and slight lower than that of ERE. The results indicated that SWE could be a productive and environmental friendly technique for extracting bioactive extracts from RP.

Tetrabromobisphenol A bis(2-hydroxyetyl) ether (TBBPA-DHEE) is among the main derivatives of Tetrabromobisphenol A (TBBPA). Result from previous study showed that TBBPA-DHEE can cause neurotoxicity in rat. In this study, zebrafish larvae were used for evaluation of TBBPA-DHEE-induced developmental toxicity, apoptosis, oxidative stress and the potential molecular mechanisms of action. Our result showed that TBBPA-DHEE exposure caused a significant concentration-dependent developmental toxicity endpoints like death rate, malformation rate, growth rate. TBBPA-DHEE altered locomotor and enzymes activities of larvae and caused apoptosis within the brain indicating the potential TBBPA-DHEE-induced cardiac, brain impairment in the zebrafish larvae. Our transcriptomic analysis shows that 691 genes were differentially expressed (DEGs) (539 upregulated, 152 downregulated). The KEGG and GO enrichment pathway analysis shows that the DEGs were involved in development, immunity, enzyme activity. Our study provides novel evidence on the neurodevelopmental toxicity and toxicity mechanism of TBBPA-DHEE which are vital for assessment of the environmental toxicity and risk assessment of the chemical.

Diabetes mellitus is a common endocrine metabolic disorder, and previous studies have shown that diabetics are more sensitive to the toxic environmental contaminants. Acrylamide (ACR) is both an industrially multipurpose compound and a common endogenous food contaminant to which people are frequently exposed and at high risk. However, the toxicity of ACR on diabetes hasn't attracted much attention. In this study, both healthy mice and diabetic mice received ACR administration orally to investigate the ACR-induced metabolic toxicity, mechanism and susceptibility to ACR toxicity in adult diabetic male mice. The results showed that ACR significantly increased FBG level and decreased bodyweight, serum lipid and liver lipid biomarkers (TC, TG, LDL-C, HDL-C) levels as well as expression of lipid and glucose metabolism-related genes in diabetic mice, indicating that ACR can exacerbate metabolic disorders of glucose and lipid in diabetic male mice. Moreover, ACR exposure significantly increased levels of MDA and COX-2), decreased GSH level and antioxidant enzyme activity (SOD, GSH-PX and CAT) by downregulating expression of Nrf2 and Keap1 in diabetic mice. Factorial analysis showed ACR had a more significant disturbance in diabetic mice compared with healthy mice. Our results indicated that ACR exposure can cause oxidative stress and inflammatory damage, which can exacerbate abnormal glucose and lipid metabolism. This work helps to elucidate the effects and underlying mechanisms of ACR-induced metabolic toxicity in adults with diabetes.

As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) is associated with various health risks, especially on immune system, which is sensitive to environmental pollutants. In addition, there is a problem of multi-index estimation and lack of comprehensive evaluation in immune toxicity study. In this study, the immunotoxicity of BDE-209 was systematically estimated from the aspects of immunopathology, humoral immunity, cellular immunity and non-specific immunity, etc., and integrated biomarker responses (IBR) combined with principal component analysis was applied to comprehensively evaluate the immunotoxicity of BDE-209 and its self-recovery after discontinuation. Results showed that BDE-209 exposure could cause immunotoxicity. This response seems to depend on (1) atrophying immune organs (thymus and spleen), hepatomegaly accompanied by increasing aspartate aminotransferase and oxidative stress;(2) changing humoral (immunoglobulins) and cellular (lymphocyte proliferation and cytokine secretion) immunity indices; (3) altering related expressions of genes, and further leading to imbalance of Th1/Th2 (Th, helper T cell). Integrated biomarker responses (IBR) companied with principal component analysis selected five biomarkers (mRNA expression of GATA-3, malondialdehyde level in thymus, count of white blood cell, serum IgG and lipopolysaccharide-induced splenic lymphocyte proliferation) to clarify the immunotoxicity induced by BDE-209. Furthermore, IBR combined with factorial analysis revealed that the effect of BDE-209 could be dose-dependently reduced after withdrawal of BDE-209. Overall results suggested that BDE-209 has immunotoxicity on adult Balb/c mice, whereas this immunotoxicity could be reduced by the self-regulation of organisms to some extent.

Dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) have been reported to exhibit reproductive toxicity in vertebrates. However, the combined effect of DBP and DiBP on offspring of exposed parents remains unclear, especially for aquatic organisms such as fish. The aims of this study were to assess the effects of parental co-exposure to DBP and DiBP on early development of zebrafish offspring, and to explore the potential molecular mechanisms involved. The early developmental indicators and transcriptomic profiles of F1 larvae were examined after parental exposure to DBP, DiBP and their mixtures (Mix) for 30 days. Results showed that parental exposure to DBP and DiBP, alone or in combination, resulted in increased hatchability at 48 hpf and heart rate at 96 hpf, and increased the prevalence of malformations and mortality in F1 larvae. Generalized linear model (GLM) suggested an antagonistic interactive effect between DBP and DiBP on mortality and malformations of F1 larvae. The transcriptomic analysis revealed that the molecular mechanisms of parental co-exposure were different from those of either chemical alone. Disruption of molecular functions involved unfolded protein binding, E-box binding and photoreceptor activity in F1 larvae. These findings provide initial insights in the potential mechanism of action of parental co-exposure to DBP and DiBP.

To explore the comprehensive utilization of agricultural wastes, solid-state fermentation was applied to residues of Flammulina velutipes (F. velutipes) and vinegar for use in culturing earthworms. Fermentation technology and earthworm culture technology were optimized by response surface methodology in this study. The optimal fermentation product for earthworm culture was obtained under an inoculum amount of 7.5%, fermentation temperature of 25.6 °C, pH 7.7 and protein content of 18.23%. The optimum culture conditions were a culture density of 18.4 individuals/dm3, an initial pH of 7.2 and a fermentation temperature of 26.8 °C. The daily weight gain multiplier of earthworms was 0.0387 units, and it increased significantly compared with that of the unfermented and cow dung groups. The fermented product of F. velutipes and vinegar residues could be used to culture earthworms and improve the metabolism and antioxidant capacities of earthworms. This provides a new way to comprehensively utilize agricultural waste resources.

Tetrabromobisphenol S (TBBPS), an emerging brominated flame retardant (BFR) has been widely detected in the environment, and may potentially pose environmental risks. However, data on the occurrence and toxic effects of TBBPS are limited. Circadian rhythms govern multiple behavioral and physiological processes, and their disruption is closely associated with various pathological conditions. Little is known about the potential for TBBPS to perturb circadian rhythm networks or circadian-driven locomotor behavior. In the present study, behavior assays and gene expression analysis based on circadian rhythm pathways were designed to investigate the potential circadian rhythm impairments and subsequent adverse effects caused in 120 h post-fertilization (hpf) zebrafish larvae by TBBPS. The development of embryos was inhibited by TBBPS exposure even at concentrations below the maximal non-lethal concentration (MNLC, 3.47 mg/L). Our results indicated remarkable alterations in the expression of several key circadian rhythm genes due to TBBPS exposure. Compared to control, the expression of per1a, per1b, per3, cry2, and csnk1da was increased, while the expression of clocka, clockb, cry4, cry1ba, arntl1a, and cank1db was decreased. Significant alterations of the circadian rhythm network could be observed in the zebrafish embryos. TBBPS exposure also significantly affected the behavioral responses of larvae. Our findings suggest the circadian rhythm network could be a potential target of TBBPS. Further study is needed to explore whether the transcriptional alterations in circadian rhythm translate into physiological effects.

In this study, a Se-deficient mice model was successfully developed by feeding a Se-deficient diet (0.02 mg Se/kg diet) for 4 weeks, and Se supplementation by Se-polysaccharides (Se-GFP-22) was lasted for 4 weeks. The immunomodulatory activity and Se supplementation of Se-GFP-22 from Se-enriched G. frondosa was investigated. Results showed that Se-GFP-22 remarkably enhanced glutathione peroxidase (GSH-Px) and thioredoxin reductase (TrxR) activities in liver, kidney and plasma, and serum, liver, spleen and kidney Se levels of Se-deficient mice. Se-GFP-22 increased the thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes and DTH reaction. Se-GFP-22 caused significant increments in cytokine (IL-1β, TNF-α and IFN-γ) levels and Ig G, Ig A, Ig M and Ig E levels. Se-GFP-22 exhibited superior immunomodulatory effects than GFP-22. These findings indicated that Se-GFP-22 promote the protective effects against Se deficiency-induced immunosuppression and could be a potential immunomodulatory agent and a dietary Se-supplement.

The structural characterization, antioxidant activity and protective effect against H2O2-induced injury RAW264.7 cells of a new polysaccharide (MP1) isolated from Lepidium meyenii Walp. were investigated. The molecular weight was estimated to be 4.67 × 105 Da by HPLC-ELSD analysis. Monosaccharide composition was determined to be arabinose and galactose in a molar ratio of 2:1 by GC-MS and PMP-HPLC-UV analysis. Methylation combined with 1D and 2D NMR spectrum analysis revealed that MP1 was an arabinogalactan. MP1 possessed a moderate antioxidant activity in vitro in DPPH, ABTS, superoxide and hydroxyl radicals scavenging, Fe2+ chelating, lipid peroxidation inhibition and reducing power assays. MP1 could also effectively protect RAW264.7 cells from H2O2-induced injury by maintaining stable cell viability, decreasing ROS, MDA and LDH level and enhancing SOD, GSH-Px and CAT activity. These results suggested the potential utilization of MP1 as a natural antioxidant for food and pharmaceutical applications.

To assess the immunomodulatory and antioxidant activities of a Se-polysaccharide from Se-enriched G. frondosa (Se-GFP-22), immunosuppressed mice models were generated by cyclophosphamide (CTX) administration and then treated with Se-GFP-22. Results showed that Se-GFP-22 could increase thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes, DTH reaction, serum hemolysin formation and immunoglobulin (Ig G, Ig A and Ig M) levels in CTX-treated mice. Se-GFP-22 significantly enhanced the antioxidant activity in CTX-treated mice, as shown by the evaluation of GSH-Px, SOD and CAT activities, as well as MDA levels in serum, liver and kidney. Se-GFP-22 strongly stimulated inflammatory cytokines (IL-2 and IFN-γ) and NO productions by up-regulating mRNA expressions of IL-2, IFN-γ and iNOS. Se-GFP-22 possessed the immunomodulatory activity by up-regulating various transcription factors (JNK, ERK, and p38) in MAPKs signaling pathways. This study suggested that Se-GFP-22 may provide an alternative strategy in lessening chemotherapy-induced immunosuppression.

Anthocyanins (ACNs) are naturally occurring components of human diet. Evidence has accumulated regarding the positive association of their intake with chronic disease. Because microbiota has been considered as a metabolic organ, the bacterial-dependent metabolisms of three types of ACNs from mulberry fruits (cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), delphinidin-3-rutinoside (D3R)) during a simulation of large intestine conditions were investigated. ACNs and metabolites were analysed and characterized by high performance liquid chromatography-electrospray ionization-mass spectrum (HPLC-ESI-MS/MS). C3G disappeared after 6h of metabolism, while C3R and D3R were no longer detected after 8h. The metabolism of C3G and C3R mainly resulted in the formation of protocatechuic, vanillic, and p-coumaric acids, as well as 2,4,6-trihydroxybenzaldehyde, while the main metabolites of D3R were gallic acid, syringic acid and 2,4,6-trihydroxybenzaldehyde. This research indicated that the intake of ACNs may result in the appearance of specific metabolites that exert a protective effect in the host physiology.

Two water-soluble polysaccharides were obtained from the leaves of Abelmoschus esculentus using aqueous extraction and purification with DEAE-52 and Sephadex G-100. AEP-11 (1.9 × 105 Da) consisted of D-arabinose, D-xylose, D-glucose, D-mannose, and D-galactose in a 2.9:3.1:0.3:0.4:3.4 ratio. AEP-22 (1.6 × 106 Da) consisted of D-arabinose, xylose, D-mannose, and galactose in a 4.7:0.8:0.6:3.9 ratio. AFM and Congo red indicated that the enhanced flexibilities of AEP-11 and AEP-22 chains could lead to agglomerated morphologies and may further confirm random coils instead of triple helical conformations. CD revealed the presence of disordered structure in AEP-22 compared with the ordered structure in AEP-11. In antioxidant activity assay, AEP, AEP-11, and AEP-22 all exhibited strong radical-scavenging capacities (AEP > AEP-11 > AEP-22) and obvious reducing power.

Our previous study revealed that the antioxidant activity of polysaccharide (coded as FGFP) extracted from Grifola frondosa by enzymolysis treatment was significantly superior than that (coded as GFP) extracted by boiling-water. In this study, one purified polysaccharide fractions (coded as FGFP-11) was obtained from FGFP by purified using DEAE-52 column and Sephacryl S-500HR column. Results indicated that FGFP-11 with MW of 59.82 kDa consisted of mannose, glucose and galactose with a molar ratio of 1.00:16.36:5.25. Fourier Transform Infrared Spectroscopy (FTIR spectrum) of FGFP-11 was similar with that of polysaccharide extracted by boiling-water from Grifola frondosa. These indicated the enzymolysis did not destroy the polysaccharide structure. NMR spectrum showed that FGFP-11 possess α-(1→6) glycosidic bond and α-(1→3) glycosidic bond configuration. The experiment of Congo red also revealed that FGFP-11 had triple helix stereo-configuration. Moreover, the antioxidant activities of FGFP-11 were improved compared with that of GFP, especially in scavenging of hydroxyl radical and diphenyl picryl hydrazinyl (DPPH) radical.

Anthocyanins (ANCs) are phytochemicals with several health effects and undergo significant degradation and subsequent biotransformation during complex metabolic processes. The aim of the present study was to determine the bioaccessibility and biotransformation of cyanidin-3-glucoside (C3G) during the simulated gastric-intestinal digestion in vitro and the metabolism in rats in vivo. Characterization of C3G and its metabolites was conducted by HPLC-ESI-MS/MS. After gastric-intestinal digestion, C3G was detected with a recovery of 88.31% in the gastric-digestive system, and a small amount of methylated-C3G occurred. In the intestinal-digestive system, C3G occurred with a recovery of 6.05%, and mainly decomposed into protocatechuic acid (PCA) and 2,4,6-trihydroxybenzaldehyde. The pharmacokinetic trial of C3G in rats showed rapid elimination in plasma. In tissues, C3G underwent rapid absorption and metabolism into phenolic acids or their derivatives. C3G and methylated-C3G passed through the blood–brain barrier and caused rapid distribution of C3G in the brain. Understanding the conversion of C3G and its metabolites helps in the future design of dietary interventions and the exploration of biological activities of ACNs.

The prevalence of adolescent type 2 diabetes mellitus (A-T2DM) is increasing year by year. Di-(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, could exacerbate type 2 diabetes mellitus (T2DM). The study aimed to investigate the metabolic toxicity, susceptibility and mechanism of DEHP exposure to A-T2DM. DEHP was administered orally (0, 0.18, 1.8, 18, and 180 mg/kg/day) for 3 weeks to adolescent normal mice (A-normal mice) and established A-T2DM mice. The results of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels showed that the susceptibility of A-T2DM mice to DEHP exposure was more significant than that of A-normal mice. DEHP, interfering with glucose and lipid metabolism of A-normal and A-T2DM mice, caused the body weight increase of A-normal mice and decrease of A-T2DM mice. Besides, DEHP could cause more injury of cardiovascular, hepatic and renal function to A-T2DM mice than A-normal mice. Hepatic transcriptome analysis revealed that DEHP exposure interfered with the biological feedback adjustment of endocrine and metabolic system in A-T2DM mice and then led to the development of T2DM. According to the transcriptome results, insulin signaling transduction pathway was applied and researched by immunoassay. It was discovered that DEHP reduced insulin sensitivity and disturbed insulin signaling transduction, glucose utilization, lipid synthesis and protein synthesis. Collectively, DEHP could disturb the endocrine and metabolic functions and increase the insulin resistance in adolescent mice. Moreover, the adolescent T2DM mice are more sensitive to DEHP-induced endocrine and metabolic toxicity than the healthy adolescent mice.

Polychlorinated biphenyls (PCBs) would do serious damage to multiple systems, while coplanar polychlorinated biphenyls, the most toxic member of the family, has been widely taken into consideration. In this study, ICR mice were fed with different doses of PCB126 to explore the underlying molecular mechanisms on immunotoxicity. The results showed that PCB126 caused immunosuppression as evidenced by inhibiting the ratios of thymus and spleen weights, changing the organizational structure and decreasing levels and mRNA expression of TNF-α, IFN-γ and IL-2. PCB126 inhibited the SOD activity and spurred the accumulation of MDA in spleen and thymus. Meanwhile, it also disturbed the Nrf2 signaling pathway as evidenced by up-regulating the mRNA expression of Nrf2 and Keap1. Additionally, a remarkable reduction in the mRNA expression of AhR and enhancement in the mRNA expression of Cyp1 enzymes (Cyp1a1, Cyp1a2 and Cyp1b1) were observed, which increased the ROS levels. PCB126 could increase protein expression of Bax, Caspase-3, Caspase-8 and Caspase-9, while the protein expression of Bcl-2 was decreased. In summary, the results indicated that PCB126 modulated the AhR signaling pathway, which interacted with apoptosis and oxidative stress to induce immunotoxicity, enrich the immunotoxicological mechanisms of PCB126.

Di-(2-ethylhexyl) phthalate (DEHP), one of the most common plasticizers, is closely associated with a high prevalence of pubertal type 2 diabetes mellitus (T2DM). Numerous studies have indicated that DEHP-induced metabolic toxicity exhibits sex differences. In this study, the sex differences in the effect of DEHP on pubertal T2DM (P-T2DM) mice, the susceptibility of female P-T2DM mice to DEHP-induced metabolic toxicity, and the underlying mechanisms were investigated. DEHP exposure exacerbated metabolic disorders in female P-T2DM mice. Factorial analysis showed that female P-T2DM mice were more sensitive to DEHP exposure than female normal mice and male P-T2DM mice. It was determined by integrated biomarker response results that female P-T2DM mice had higher risks of developing T2DM, metabolic disorders, cardiovascular events and hepatotoxicity than male P-T2DM mice. Moreover, hepatic transcriptome analysis emphasized the effects of DEHP on the expression of oxidative injury- and metabolic function-related genes. Western blotting indicated that DEHP activated Jun-N-terminal kinase (JNK) and impaired insulin sensitivity in the liver, which were the main causes of DEHP-exacerbated metabolic abnormalities in P-T2DM mice. Our study revealed that compared with normal mice and male P-T2DM mice, female P-T2DM mice tend to suffer from increased DEHP-induced metabolic toxicity, which was primarily attributed to hepatotoxicity.

An efficient ultrasonic-cellulase-assisted extraction (UCE) of Cistanche tubulosa polysaccharide (CTP) was established. The response surface methodology based on Box-Behnken Design was employed to further optimize extraction conditions. After quaternary ammonium salt precipitation, the polysaccharide of C. tubulosa was characterized by different techniques. The results showed that a maximum polysaccharide yield of 22.31±0.45% was achieved at a pH of 5.2 for 31.5min at 54.1°C. Compared to hot water extraction, the yield of CTP in UCE and polysaccharide content increased to 44.96% and 70.13±2.19%, respectively. There was no marked difference among polysaccharides extracted using different methods from the infrared spectrum. Ultrasonic-cellulase-assisted extraction polysaccharide showed a fibrous structure from scanning electron microscopy and was composed of rhamnose, mannose, glucose, and galactose in a molar ratio of 2.18:1:28.29:1.43 by gas chromatography. The circular dichroism results indicated that polysaccharides had a maximum positive peak around 210nm with different peak values. The thermogravimetric analysis and differential scanning calorimetry were used to test the thermostability of CTP. Besides, CTP demonstrated appreciable antioxidant potential on antioxidant experiments in vitro. The results suggested that UCE is an effective method for CTP extraction and its polysaccharide showed appreciable antioxidant activity.

In our previous study, a polysaccharide was extracted from Schisandra Chinensis (Trucz.) Baill and found with anti-diabetic effects. The aim of this study was to investigate the anti-diabetic effects of the low weight molecular polysaccharide (SCPP11) purified from crude Schisandra polysaccharide and illustrate the underlying mechanism in buffalo rat liver cells. The insulin resistance model of BRL cells was established by incubating with insulin solution for 24h. The effects of SCPP11 on regulating related protein and mRNA expression in an insulin and AMPK signal pathway were investigated by western blot and RT-PCR analysis. SCPP11 showed no cytotoxicity to BRL cells and could improve the glucose consumption in BRL cells. SCPP11 increased the protein expression of Akt, p-AMPK and GLUT-4 in BRL cells. Moreover, SCPP11 could enhance the mRNA expression levels of IRS-1, PI3K, Akt, GLUT-4, AMPKα and PPAR-γ in BRL cells at the same time. In conclusion, SCPP11 possessed effects in improving glucose consumption by up-regulating the expression of GLUT-4 which might occur via insulin and AMPK signal pathway and could be a potential functional food to prevent and mitigate the insulin resistance condition.

The rational for the study was to review the literature on the toxicity and corresponding mechanisms associated with lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As), individually and as mixtures, in the environment. Heavy metals are ubiquitous and generally persist in the environment, enabling them to biomagnify in the food chain. Living systems most often interact with a cocktail of heavy metals in the environment. Heavy metal exposure to biological systems may lead to oxidation stress which may induce DNA damage, protein modification, lipid peroxidation, and others. In this review, the major mechanism associated with toxicities of individual metals was the generation of reactive oxygen species (ROS). Additionally, toxicities were expressed through depletion of glutathione and bonding to sulfhydryl groups of proteins. Interestingly, a metal like Pb becomes toxic to organisms through the depletion of antioxidants while Cd indirectly generates ROS by its ability to replace iron and copper. ROS generated through exposure to arsenic were associated with many modes of action, and heavy metal mixtures were found to have varied effects on organisms. Many models based on concentration addition (CA) and independent action (IA) have been introduced to help predict toxicities and mechanisms associated with metal mixtures. An integrated model which combines CA and IA was further proposed for evaluating toxicities of non-interactive mixtures. In cases where there are molecular interactions, the toxicogenomic approach was used to predict toxicities. The high-throughput toxicogenomics combines studies in genetics, genome-scale expression, cell and tissue expression, metabolite profiling, and bioinformatics.

There is a great demand for developing efficient extraction methods to reduce the extraction time and increase the yields and activities of functional antioxidants. The yields, physicochemical, functional properties and antioxidant activities of ultrasound-pretreated porcine cerebral hydrolysate peptides (UPCHPs) were studied and compared with traditional enzymolysis (PCHPs). The results showed that UPCHPs had higher peptides concentration, smaller molecular weight, and higher concentration of hydrophilic and late-eluting hydrophobic peptides than PCHPs at hydrolysis time of 20 min. However, the contents of antioxidant amino acids (Gly, Ala, Arg, Pro, His, Val, Leu, Lys and Phe) in both hydrolysate peptides were above 60%. UPCHPs with an excellent solubility had high reducing power activity and scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (72%), 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals (73%) and hydroxyl radicals (56%) at 2 mg/mL. Moreover, UPCHPs showed the moderate iron chelating activity (60%). In general, UPCHPs with good functional properties could serve as a potential antioxidant food ingredients.

A polysaccharide termed Se-GP11 was extracted and purified from Se-enriched Grifola frondosa in our previous study. This study investigated the characterization, anti-tumor and immunomodulatory activity of Se-GP11. The results showed that Se-GP11 was composed of mannose, glucose and galactose with a molar ratio of 1:4.91:2.41. The weight-average molecular weight (Mw) and weight-average mean square radius (Rw) of Se-GP11 in 0.1M sodium chloride solution were 3.3×10(4)Da and 32.8 nm. Se-GP11 existed as a globular conformation with random coil structure. Se-GP11 had no anti-tumor activity against HepG-2 cells in vitro, and it significantly inhibited the growth of Heps tumor in vivo. Se-GP11 increased the relatively thymus and spleen weights as well as serum necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) levels. In addition, Se-GP11 promoted the phagocytosis and NO production of RAW264.7 as compared with that of the normal control group. The results revealed that the Se-GP11 may exhibit the anti-tumor through improving immunologic function of the tumor bearing mice.

Dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) are phthalate compounds frequently detected in the environment. Despite increasing awareness of their toxicity in human and animals, the male reproductive toxicity of their combined exposure remains elusive. The purposes of this study were to investigate whether combined exposure to DBP and DiBP could induce male reproductive toxicity, and to explore the potential toxicological mechanisms. Adult male zebrafish were exposed to DBP (11, 113 and 1133 μg L−1), DiBP (10, 103 and 1038 μg L−1) and their mixtures (Mix) (11 + 10, 113 + 103, 1133 + 1038 μg L−1) for 30 days, and their effects on plasma hormone secretion, testis histology and transcriptomics were examined. Highest concentrations of Mix exposure caused greater imbalance ratio of T/E2 and more severe structural damage to testis than single exposure. These effects were consistent with the testis transcriptome analysis for which 4570 genes were differentially expressed in Mix exposure, while 2795 and 1613 genes were differentially expressed in DBP and DiBP, respectively. KEGG pathway analysis showed that both single and combined exposure of DBP and DiBP could affect cytokine-cytokine receptor interaction. The difference was that combined exposure could also affect steroid hormone synthesis, extracellular matrix receptor interaction, retinol metabolism, and PPAR signaling pathways. These results demonstrated that combined exposure to DBP and DiBP could disrupt spermatogenesis and elicit male reproductive toxicity in zebrafish.

Correction for ‘Bioaccessibility and biotransformation of anthocyanin monomers following in vitro simulated gastric-intestinal digestion and in vivo metabolism in rats’ by Yao Chen et al., Food Funct., 2019, 10, 6052–6061, DOI: 10.1039/C9FO00871C.

Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer which could be easily absorbed by humans and animals through various channels. It has been found that exposure to DEHP could increase the incidence of insulin resistance. In this study, therefore, the metabolism toxicity, susceptibility and mechanism of DEHP (5500 and 50,000 nM exposure for 24 h) on normal BRL cells (Buffalo Rat Liver cells) and BRL cells with insulin resistance induced by insulin were investigated. The results showed that DEHP could cause cell damage with ALT and AST activities and MDA levels increased, cell apoptosis with Caspase-3 levels increased and insulin resistance with IR-β levels decreased in BRL cells with resistance and normal BRL cells. Western-blot analysis and Q-PCR showed that the levels and gene expressions of insulin signaling proteins (IRS-1, GLUT4, GSK-3α, GSK-3β, PI3K, AKT, mTOR), cell signaling proteins (RAS, ERK1/2, MEK1/2, BAD, BAX, BCL-2) and immediate early genes in insulin resistance cells and normal cells were significantly altered by DEHP. DEHP significantly promoted serine phosphorylation of IRS-1. The insulin resistance cells in metabolism toxicity were more sensitive to DEHP than normal cells. Intervention with insulin could improve the metabolism toxicity and insulin resistance. The results indicated that DEHP exerted metabolic toxic effects and increased insulin resistance through interfering with glucose metabolism and insulin signaling transduction pathway. Moreover, the risks of DEHP-induced metabolic toxicity and insulin resistance in BRL cells with insulin resistance were higher than that of normal BRL cells.

Phthalates (PAEs) in drinking water sources such as the Yangtze River in developing countries had aroused widespread concern. Here, the water, suspended particulate matter (SPM), and sediment samples were collected from 15 sites in wet and dry seasons in Zhenjiang, for the determination of six PAEs (DMP, DEP, DIBP, DBP, DEHP, and DOP) using the solid-phase extraction (SPE) or ultrasonic extraction coupled with gas chromatography-mass spectrometry (GC-MS). The total concentrations of six PAEs (Σ6PAEs) spanned a range of 2.65-39.31 μg L-1 in water, 1.97-34.10 μg g-1 in SPM, and 0.93-34.70 μg g-1 in sediment. The partition coefficients (Kd1) of PAEs in water and SPM phase ranged from 0.004 to 3.36 L g-1 in the wet season and from 0.12 to 2.84 L g-1 in the dry season. Kd2 of PAEs in water and sediment phase was 0.001-9.75 L g-1 in the wet season and 0.006-8.05 L g-1 in the dry season. The dominant PAEs were DIBP, DBP, and DEHP in water and SPM, DIBP, DEHP, and DOP in sediment. The concentration of DBP in water exceeded the China Surface Water Standard. The discharge of domestic sewage and industrial wastewater might be the main potential sources of PAEs. The risk quotient (RQ) method used for the risk assessment revealed that DBP (0.01 1) posed a high environmental risk in water, DIBP (RQ > 1) also showed a high risk in sediment.

Dioctyl phthalate (DOP) (200, 500, and 1000 mg kg-1 bw, i.g.), Pb (Ac)2 (50 mg L-1, p.o.), and NaAsO2 (10 mg L-1, p.o.) were administered individually and as mixtures to weanling male mice for 8 weeks. It was observed that Pb, As, and DOP exposure could significantly inhibit the growth and development of mice. Compared with the Pb, As, and Pb + As groups, the activities of iNOS and TNOS were significantly increased, the levels of AChE and SOD were significantly decreased, and the level of MDA was significantly increased in the Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups. The factorial analysis shows that the iNOS, TNOS, and AChE present synergistic effects on Pb, As, and DOP. A significant increase of escape latency and a significant decrease of original platform quadrant stops were observed between Pb + As + DOP-H and Pb + As groups. The factorial analysis shows that there was a synergistic effect on Pb, As, and DOP. Compared with that of the control group, the expression levels of caspase-3 and Bax expression in Pb + As, DOP-H, Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups were significantly increased in the hippocampus. The expression levels of Bcl-2 expression decreased significantly and the Bax/Bcl-2 ratio increased significantly. Pathological alterations on the hippocampus were found in exposed groups. This result shows that combined exposure of Pb, As, and DOP could induce neurotoxicity, of which possible mechanism is hippocampal neuronal apoptosis. Graphical abstract This study shows that there were three components with eigenvalues greater than 1, which together explained 89.40% of total variance. The first component (PC1) showed high loadings on B-SOD, L-SOD, B-MDA, L-MDA, K-MDA, iNOS, tNOS, and AChE and accounted for 46.55% of the total variance after Varimax rotation. PC2 accounted for 23.81% of the total variance with high loadings on B-As, L-As, K-As, and K-SOD, whereas PC3 showed high loadings on B-Pb, L-Pb, and K-Pb and accounted for 19.04% of the total variance.