To mitigate the health risks of lunar dust toxicity to astronauts during future lunar missions, understanding the biodistribution of its primary component, silicon dioxide (SiO2), is crucial. This study examined the short-term behavior of SiO2 nanoparticle (SiO2-NP) in biological systems using male Sprague–Dawley (SD) rats. The rats were divided into control, high-dose, and low-dose groups. The rats were divided into control, high-dose, and low-dose groups. The experimental groups received a single intratracheal instillation of SiO2-NP. Blood, lungs, spleen, liver, and kidney samples were collected at designated time points post-exposure. Toxicokinetics (TK) and biodistribution of SiO2-NP were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Results showed a dose-dependent behavior of SiO2-NP in the body. In the high-dose group, SiO2-NP accumulated mainly in the lungs with slower absorption and excretion, leading to prolonged retention. The low-dose group showed faster systemic distribution and excretion, with higher initial excretion rates. SiO2-NP distribution varied dynamically over time, initially concentrating in the lungs and then spreading to the liver, kidneys, spleen, and heart. Urinary excretion data indicated primary elimination through the kidneys, with more efficient excretion in the low-dose group. The findings suggest that slow clearance of SiO2-NP in the high-dose group may increase toxicity risk, while the low-dose group exhibits quicker distribution and excretion, albeit with potential systemic toxicity risks. This study highlights the short-term biodistribution of SiO2-NP, providing key insights into its potential risks and supporting further research on lunar dust toxicity.

Epoxiconazole (EPX) is widely applied to control various fungal diseases in crops. However, the toxicological effects of EPX on reptiles remain unknown, especially at the enantiomer level. In this study, lizards were repeatedly exposed to rac-EPX, (+)-EPX, and (-)-EPX at doses of 10 and 100 mg/kg bw for 21 days. Low-dose exposure resulted in hepatic steatosis, while high-dose treatment caused more severe pathological changes, including large areas of cell necrosis, loss of cellular structure, and nucleus disappearance. The elevation of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) indicated hepatocyte impairment after high-dose exposure. Furthermore, increased levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) suggested oxidative damage to lipids and DNA in cells, respectively. In addition, the EPX-induced hepatotoxicity exhibited significant enantioselectivity, with injury severity ranked as follows: rac-EPX > (-)-EPX > (+)-EPX. Notably, the highest hepatotoxicity in lizards was attributed to rac-EPX, suggesting a synergistic effect of rac-(+)-EPX and rac-(-)-EPX. The hepatotoxicity induced by (+)-EPX in lizards was lower than that of (-)-EPX, but with higher fungicidal activity. Therefore, it is advisable to utilize (+)-EPX in agricultural production. This study provides a scientific basis for the environmental risk assessment of EPX and the development of future optically pure pesticides.

The present study aimed to establish a physiologically based toxicokinetic (PBTK) model to investigate the absorption, retention, and transport of inhaled nano-sized titanium dioxide (TiO2-NPs) particles in rats, thereby providing a basis for understanding the absorption, distribution, and elimination mechanisms of TiO2-NPs in various organs. A detailed respiratory module and the Hill coefficient equation were adopted in the PBTK model. Calibration and validation of the model were conducted using the only two available inhalation biodistribution datasets for TiO2-NPs found in the literature, encompassing different doses and exposure conditions. The overall fit with both datasets was acceptable with R2 value of 0.95 in respiratory system and 0.88 in the secondary organs. The sensitivity analysis indicated that the alveolar–interstitial transfer rate (Kalv_inter) and tissue–blood distribution coefficients (Plu, Pli, Pki) significantly influenced the retention of TiO2-NPs in pulmonary regions and distribution to secondary organs, with these parameters exhibiting time-dependent behavior. The PBTK model demonstrates a good predictive performance for TiO2-NPs content in all rat organs, with simulated values consistently ranging within 0.5- to 2-fold of the measured data. In last, we developed a PBTK model that can well predict the in vivo distribution of inhaled TiO2-NPs and provided a novel computational tool for cross-species extrapolation of human inhalation exposure and subsequent biodistribution.

Pyrifluquinazon (PFQ), a novel insecticide containing a heptafluoroisopropyl moiety, has seen increasing use. However, limited research has been conducted on the toxicological effects and mechanisms of PFQ in aquatic organisms. To investigate the toxicity and underlying mechanisms of PFQ and its primary metabolite dPFQ in aquatic organisms, morphological, behavioral, hormonal, multi-omics analyses, and molecular docking studies were conducted on zebrafish larvae after exposure. The results showed that both PFQ and dPFQ induced developmental abnormalities, behavioral impairment, hormonal disruptions, and alterations in neurologically related metabolites and gene expression in early-stage zebrafish. Notably, delayed retinal vascular development was observed, which is also likely linked to the neurodevelopmental toxicity. Subsequently, identification and relative quantification of PFQ metabolites suggested that its toxicity might be primarily attributed to dPFQ. Finally, an Adverse Outcome Pathway (AOP) was proposed, initiating with the binding of dPFQ to the TRPV4 protein and ultimately leading to neurodevelopmental toxicity. This study delineated the neurodevelopmental toxicity of PFQ and its toxicological mechanisms in zebrafish, emphasizing the hazards posed by pesticide metabolites to non-target organisms and highlighting inherent limitations of extrapolating in vitro toxicity experiments.

Preventing soil nitrogen (N) losses driven by microbial nitrification and denitrification contributes to improving global environmental concerns caused by NO3−-N leaching and N2O emission. Quorum sensing (QS) signals regulate nitrification and denitrification of N-cycling bacteria in pure culture and water treatment systems, and mediate the composition of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in activated sludge. However, whether disrupting QS could prevent soil N losses remains unclear. This study explored the feasibility of applying quorum sensing inhibitors (QSIs) as an innovative strategy to reduce N losses from agricultural soils. The two QSIs, penicillic acid and 4-iodo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]-benzeneacetamide (4-iodo PHL), were more effective in reducing N losses than traditional inhibitors, including N-(n-butyl) thiophosphoric triamide and 3,4-dimethylpyrazole phosphate. After 36 days of aerobic incubation, penicillic acid and 4-iodo PHL inhibited nitrification by 39% and 68%, respectively. The inhibitory effects are attributed to the fact that 4-iodo PHL decreased the abundance of archaeal and bacterial amoA genes, as well as the relative abundance of Candidatus Nitrocosmicus (AOA), Candidatus Nitrososphaera (AOA), and Nitrospira (nitrite-oxidizing bacteria/comammox), while penicillic acid reduced archaeal amoA abundance and the relative abundance of Nitrosospira (AOB) and the microbes listed above. Penicillic acid also strongly inhibited denitrification (33%) and N2O emissions (61%) at the peak of N2O production (day 4 of anaerobic incubation) via decreasing nitrate reductase gene (narG) abundance and increasing N2O reductase gene (nosZ) abundance, respectively. Furthermore, the environmental risks of QSIs to microbial community structure and network stability, CO2 emissions, and soil animals were acceptable. Overall, QSIs have application potential in agriculture to reduce soil N losses and the associated effect on climate change. This study established a new method to mitigate N losses from the perspective of QS, and can serve as important basis of decreasing the environmental risks of agricultural non-point source pollution.

Ethiprole is widely used as a second-generation phenyl pyrazole insecticide. Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites (ethiprole sulfone (M1) and ethiprole sulfide (M2)) of ethiprole showed higher acute toxicity than ethiprole. Therefore, assessing the thyroid toxicity of its metabolites is crucial for safety assessment. In this study, the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico, in vitro, and in vivo assays, with the aim of conducting a comparative study on thyroid toxicity. Molecular docking analysis showed that ethiprole, M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3',5-triiodothyronine (T3). GH3 cell proliferation assays revealed that ethiprole, M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation. Using the zebrafish model, we further investigated that exposure to ethiprole, M1, and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid (HPT) axis-related genes. Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta, M1 mainly through binding with the corticotropin releasing factor receptor-1, and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity. M2 showed the highest developmental toxicity and thyroid disrupting effects, which significantly reducing hatching rates, increasing deformity rates, exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis. This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.

Sponges are the most basal metazoan phylum1 and may have played important roles in modulating the redox architecture of Neoproterozoic oceans2. Although molecular clocks predict that sponges diverged in the Neoproterozoic era3,4, their fossils have not been unequivocally demonstrated before the Cambrian period5-8, possibly because Precambrian sponges were aspiculate and non-biomineralized9. Here we describe a late-Ediacaran fossil, Helicolocellus cantori gen. et sp. nov., from the Dengying Formation (around 551-539 million years ago) of South China. This fossil is reconstructed as a large, stemmed benthic organism with a goblet-shaped body more than 0.4 m in height, with a body wall consisting of at least three orders of nested grids defined by quadrate fields, resembling a Cantor dust fractal pattern. The resulting lattice is interpreted as an organic skeleton comprising orthogonally arranged cruciform elements, architecturally similar to some hexactinellid sponges, although the latter are built with biomineralized spicules. A Bayesian phylogenetic analysis resolves H. cantori as a crown-group sponge related to the Hexactinellida. H. cantori confirms that sponges diverged and existed in the Precambrian as non-biomineralizing animals with an organic skeleton. Considering that siliceous biomineralization may have evolved independently among sponge classes10-13, we question the validity of biomineralized spicules as a necessary criterion for the identification of Precambrian sponge fossils.

Epoxiconazole (EPX) is a world widely used chiral triazole fungicide in the agriculture field. The excessive application of this triazole may cause damage to lizards. However, limited information is known about the toxicokinetics of EPX on lizards. Our study aimed to investigate the enantioselective absorption, distribution, metabolism, and elimination (ADME) of EPX in lizards following low and high dose exposure (10 and 100 mg kg−1 bodyweitht (bw)). The results demonstrated that (+)-EPX was easier absorbed than (−)-EPX in lizard plasma. Both (+)-EPX and (−)-EPX were detected in the liver, gonad, kidney, skin, brain, and intestine, with (+)-EPX preferentially distributed in these tissues. The elimination of (−)-EPX was faster than that of (+)-EPX in lizard liver and kidney in the high dose groups. Chiral conversion was found between EPX enantiomers in lizard skin. Simultaneously, five metabolites including M2, M4, M10, M18 and M19 were detected in lizard liver and kidney after EPX enantiomers exposure. The relative concentrations of M2, M4, and M10 were higher in the liver and kidney of (−)-EPX groups than those produced from (+)-EPX groups. The metabolic enzymes CYP3A4 and SULT1A1 primarily mediated enantioselective metabolism of EPX. The conclusions drawn from this study significantly enhance our understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles, offering essential guidance for assessing the risks associated with different enantiomers of triazole fungicides.

Previous studies have demonstrated the reproductive toxicity of trifluorostrobin (TRI) in male organisms. However, the underlying mechanisms of TRI responsible for testicular damage and hormonal disruption remain elusive. This study elucidated the male reproductive toxicity of TRI at the molecular level under environmentally relevant concentrations and its associations with gut microbiota dysbiosis. The rats were administered TRI (1.5, 15, and 75 mg/kg of body weight/day) continuously via gavage for 90 days. Exposure to 15 mg/kg (below the no-observed adverse effect level (NOAEL) of 30 mg/kg) and 75 mg/kg TRI damaged testicular tissue, reduced sperm count, and lowered serum hormone and total cholesterol levels. Transcriptomics analysis combined with molecular docking simulations and cell proliferation assays showed that exposure to TRI led to testicular damage by inhibiting the expression of cholesterol receptor genes, which, in turn, disrupted steroid hormone biosynthesis. Furthermore, exposure to TRI resulted in a marked decline in the relative abundance of the probiotic bacteria. Consistently, significant reductions in the relative abundance of short-chain fatty acids (SCFAs), retinoic acids, and steroid hormones in the gut were observed. Additionally, a significant correlation was observed between the relative abundance of Parabacteroides and serum testosterone levels, a vital biomarker for reproductive toxicity monitoring. These findings shed light on the mode of action of TRI-induced male reproductive toxicity and highlight the link between testicular injury and gut microbiota.

Previous studies have indicated that tire wear particles (TWPs) leachate exposure induced serious eye injury in fish through inhibiting the thyroid peroxidase (TPO) enzyme activity. However, the main TPO inhibitors in the leachate were still unknown. In this study, we identified 2-Mercaptobenzothiazole (MBT) as the potential TPO inhibitor in the TWPs leachate through references search, model prediction based on Danish QSAR and ToxCast database, molecular docking, and in vivo assay. We further explored the toxic mechanism of MBT under environmentally relevant concentrations. The decreased eye size of zebrafish larvae was mainly caused by the decreased lens diameter and cell density in the inner nuclear layer (INL) and outer nuclear layer (ONL) of the retina. Transcriptomics analysis demonstrated that the eye phototransduction function was significantly suppressed by inhibiting the photoreceptor cell proliferation process after MBT exposure. The altered opsin gene expression and decreased opsin protein levels were induced by weakening thyroid hormone signaling after MBT treatment. These results were comparable to those obtained from a known TPO inhibitor, methimazole. This study has identified MBT as the primary TPO inhibitor responsible for inducing eye impairment in zebrafish larvae exposed to TWPs leachate. It is crucial for reducing the toxicity of TWPs leachate in fish.

N-(1,3-Dimethylbutyl)-N '-phenyl-1,4-phenylenediamine (6PPD) and its oxidation product 6PPD-quinone (6PPDQ) showed different acute toxicities and bioaccumulation potencies in fish. In this study, we compared the thyroid disrupting effects of 6PPD and 6PPDQ through in vitro, in silico, and in vivo assays. Interestingly, although 6PPD and 6PPDQ showed similar docking affinities with thyroid hormone receptor (TR) isoforms and GH3 cell inhibition effects, the thyroid signaling pathway, eye development, phototactic behaviors, and cell density in the retinal layer in the larval zebrafish were significantly affected only following 6PPD exposure. Further investigation demonstrates that 6PPD can act as a TR antagonist to reduce the opsin protein abundance and inhibit the cone photoreceptor cell proliferation, which finally alters the retinal layer structure and causes microphthalmus in zebrafish. Especially, under environmental relevant concentration exposure, 6PPD induced alterations of tr beta, opn1lw1, opn1mw1, rpe65a, nr2e3 gene expressions although no significant eye histopathological change was observed. This study illustrates for the first time the more serious visual system impairment of 6PPD compared to 6PPDQ, with thyroid signaling disruption being a contributing factor, while other important toxic targets still require further research.

Evaporites are climate-sensitive sedimentary deposits with event stratigraphic, paleogeographic, and paleoenvironmental significance. The Early Cambrian is characterized by early evolution of animal and extensive evaporite deposits at the end. Widespread evaporite deposits were developed in the lower Cambrian succession in the North China Craton (NCC), which could provide critical constraints on the age of evaporite-bearing strata, the reconstruction of paleogeographic evolution, and the paleoenvironmental change of the NCC during the Early Cambrian. In this study, we systematically synthesized the geographical and stratigraphic distributions of the Early Cambrian evaporite deposits in the NCC based on field collections and published data. The results show that the Early Cambrian evaporite deposits in the NCC mainly include gypsum, halite pseudomorph, and gypsum breccia. They have been found in two sets of reddish layers and geographically distributed in the Jiao-Liao-XuHuai region and western Henan region. Integrated evidence of biostratigraphy, chemostratigraphy, and detrital zircon chronology constrains the age of these evaporite deposits within the Cambrian Series 2, Stage 4 (ca. 514-509 Ma). Consequently, these late Early Cambrian evaporite deposits represent drought events that can act as regional event stratigraphic markers to constrain the age of the evaporite-bearing strata near the Great Unconformity and also suggest that the paleogeographic position of the NCC in the Cambrian Stage 4 may be located between 20 degrees N-30 degrees N near the western Gondwana with northwest-southeast orientation. Additionally, the hot-arid paleoclimate evidenced by evaporite deposits may be the environmental factors for the decline of benthic organisms in the NCC in the late Early Cambrian.

The Great Unconformity at the Precambrian-Cambrian boundary has been recognized on several continents and may provide critical insights into the environmental context of the Cambrian explosion. However, the geodynamic drivers, geochronological duration, and paleogeographic extent of the Great Unconformity remain unconstrained in many cases. Recently, a major depositional gap of varying magnitudes has been reported around the Precambrian-Cambrian boundary in several regions of North China, leading to the interpretation that the Great Unconformity may have been widespread but diachronous across the North China Craton. However, the magnitude of the Great Unconformity remains unknown in northeastern North China, largely because of the poor age constraints on the thick Proterozoic-Cambrian successions in this region. Here we use biostratigraphic data to constrain the depositional age of Proterozoic strata below the Great Unconformity in northeastern North China. We report a diverse organic-walled microfossil assemblage from the Qinggouzi Formation in southern Jilin Province, northeastern margin of the North China Craton. Typical late Mesoproterozoic to early Neoproterozoic microfossils, including Trachyhystrichosphaera aimika and Proterocladus antiquus, are present in Qinggouzi assemblage, providing a solid biostratigraphic constraint on the Qinggouzi Formation. Given that the overlying Shuidong Formation contains typical early Cambrian small shelly fossils, our new data indicate that the Great Unconformity in northeastern North China represents a major depositional gap of >200 Myr. Thus, the new data, along with other available biostratigraphic and geochronological data from over the world, provide robust constraints on the paleogeographic extent, chronostratigraphic duration, and diachronous nature of the Great Unconformity.

The Proterozoic witnessed the emergence and rise of early eukaryotes and Proterozoic carbonaceous compression macrofossils provide a valuable window for our understanding of this ecological expansion. Among them, the discoidal Chuaria and tomaculate Tawuia, which often co-occur in the same bedding layer, are perhaps the most common fossil forms in Proterozoic successions with extremely long temporal and broad geographical distributions. However, their phylogenetic interpretations and the relationship between them have been debated for decades, due to their simple morphologies lacking phylogenetically diagnostic features. In this study, we used an integrated application of reflected and transmitted light microscopy, scanning electron microscopy, biometric analysis, and Raman spectroscopy to characterize well-preserved carbonaceous compression macrofossils of Chuaria and Tawuia from the Tonian Liulaobei Formation in Huainan region, northern Anhui province, North China. The fossils are abundantly preserved in a ca. 1-2 cm thick homogeneous mudstone layer and can be considered to be closer to an ecological community than fossils from multiple different layers or localities. The comprehensive analysis shows that even Chuaria vesicles from the same layer may have a polyphyletic origin and three groups of Chuaria vesicles have been identified. Among them, small Chuaria vesicles with minimum diameter < 1.2 mm can be either related to the sphaeromorphic acritarch Leiosphaeridia or interpreted as multicellular aggregates. In contrast, large Chuaria vesicles with minimum diameter >= 1.2 mm are more comparable to the type material of Chuaria circularis from the Chuar Group and more closely related, either phylogenetically or ontogenetically, to Tawuia vesicles. This study takes a step on the path to solving the mystery of the most common and widely distributed Proterozoic macrofossil assemblage (i.e., Chuaria-Tawuia assemblage), and urges thorough and systematic evaluations to be taken on the possibility that Chuaria vesicles from the same Chuaria-Tawuia assemblages or sole Chuaria assemblages in other localities might also be polyphyletic.

As a phenylpyrazole insecticide, flufiprole is an important substitute for fipronil in the agricultural field of China. However, its bioaccumulation and metabolism in terrestrial organisms especially in the lizards living in the agricultural area have rarely been investigated. As an ectothermic animal, lizards are also sensitive to temperature changes. Considering global warming, this study measured bioaccumulation, metabolism, and hepatotoxicity of flufiprole in the Chinese native lizard (Eremias argus) under different temperature stresses. Lizards exposed to flufiprole-contaminated soil adsorbed flufiprole through the skin and flufiprole was preferred to accumulate in lizard liver and brain. The oxidation product fipronil sulfone was the main metabolite of flufiprole in both lizard liver and human liver microsomes, which were mainly metabolized by lizard CYP3A19 or human CYP3A4. The fipronil sulfone concentration increased with increased temperature in lizard tissues. In addition, more serious oxidative damage was shown under higher temperature as the glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in lizards increased with increased temperature after flufiprole exposure. Flufiprole exposure also induced lizard liver lesions, and these lesions became more serious in the higher-temperature groups. This study provided new insights into the risk assessment of flufiprole in lizards under global warming.

Tire wear particles (TWP) have become the major microplastic pollution in China. Road runoff containing TWP leachate can decrease the eye size and even induced mortality in the aquatic organisms. However, the toxic mechanism of TWP and road particles (RP) leachate on aquatic organisms is still unclear. In this study, the zebrafish embryos were exposed to TWP or RP leachate for 5 days at both environmental relevant and high concentrations. The adverse outcome pathways (AOPs) were screened from individual to molecular levels. The morphological and behavioral analysis demonstrated that the leachate exposure mainly impaired the eye development of zebrafish larvae and inhibited the larval swim behavior and phototactic response, which are the adverse outcomes. The phototransduction modulated by zebrafish retina was significantly down-regulated through transcriptomics and metabolomics analysis. The eye histopathological analysis showed that the decreased thickness of the retinal outer nuclear layer (ONL) and retinal pigmented epithelium (RPE) after leachate exposure were caused by the decreased photoreceptor cells. Moreover, the expression of NR2E3 and TPO genes showed concentration-dependent down-regulation after leachate exposure. The inhibition of photoreceptor cell proliferation was identified as the main reason for photoreceptor cell decrease in zebrafish larval eye. This study, for the first time, uncovered the underlying toxic mechanism of TWP and RP on zebrafish larval eyes.

Common members of Proterozoic macrofossil assemblages usually include discs and tubes. Particularly, discoidal forms (e.g., Chuaria and abundant unnamed discs) and tubular forms (e.g., Tawuia and the worm-like annulated taxa Protoarenicola, Pararenicola, and Sinosabellidites) dominate most Tonian macrofossil assemblages. Previous work on Proterozoic materials indicated that some discoidal fossils could be detached holdfasts of co-occurring erect benthic organisms, e.g., some tubular fossils and frondose fossils, but little attempt has been made to quantify the potential relationship between the discoidal fossils and the discoidal holdfasts of tubular fossils from Tonian successions. In this study, we find biometric and chemospatial links between discoidal fossils with a central opening and worm-like annulated tubular fossils from the Tonian Jiuliqiao Formation (similar to 950-720 Ma) in Huainan region, northern Anhui province, North China, which supports the notion that discoidal fossils represent detached holdfasts of tubular fossils and that tubular fossils with or without a holdfast share a potential biological or ontogenic relationship. The paleoecological implication of possible holdfast coalescence (physical contact and fusion of two or more adjacent holdfasts) for Pre-Cryogenian benthic ecosystem and the evolutionary implication of this study for other Proterozoic enigmatic discoidal fossils, particularly for those with a central opening or circular ring, are discussed. Detached holdfasts and holdfast coalescence may be more common than we have thought in the Pre-Cryogenian, and the paleoecological and geobiological role of benthic algae and their holdfasts during this period is probably underestimated. Our study also highlights the adaptation of holdfast morphology to Precambrian mat-ground substrate, and provides evidence for the co-evolution of substrate and benthic organismic morphology during this period.

Tetrachlorobisphenol A (TCBPA), a widely used halogenated flame retardant, is frequently detected in environmental compartments and human samples. However, unknown developmental toxicity and mechanisms limit the entire understanding of its effects. In this study, zebrafish (Danio rerio) embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics, behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms. We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor (ECM-receptor) interaction pathways through transcriptomic analysis. Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae. Morphological observations revealed that TCBPA could cause the loss of head blood vessels. Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity. Our study demonstrated that by using omics, TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified.

1,3-二苯胍(1,3-diphenyl guanidine,DPG)是橡胶生产过程中添加的硫化促进剂,在水环境中广泛存在.然而作为水环境中的一种污染物,目前DPG对水生生物的毒性及其机制的研究极为匮乏.为了研究DPG对水生生物的生殖发育毒性及潜在机制,选择水生模式生物斑马鱼(Danio rerio)作为受试生物.将斑马鱼胚胎分别暴露于浓度为30、100和300 μg·L-1的DPG溶液中120 h,通过转录组测序、基因表达水平定量分析及性激素水平测定(雌二醇和睾酮)来探究其对斑马鱼早期生命阶段的生殖发育毒性及机制.转录组测序结果表明,DPG暴露可以显著影响与精卵识别及生殖细胞发育相关的生物学过程.DPG暴露使类固醇合成通路相关基因(cyp11a1、cyp17a1、cyp19a1a、hsd17b1、ar)的转录表达显著上调.激素结果表明DPG暴露导致斑马鱼仔鱼体内雌二醇水平显著升高.以上研究结果表明,在分子水平上,DPG能够影响斑马鱼胚胎及仔鱼的发育,但是在个体水平上仍然缺乏直接的证据揭示DPG暴露对斑马鱼生殖和胚胎发育的不良结局.本研究为DPG对水生生物的毒性研究奠定了一定的基础,并为轮胎磨损颗粒的毒性研究提供了新的线索.

Neonicotinoids is the most widely used insecticide, its contamination has led to sustained bird population declines. However, the toxicokinetic and underlying mechanisms of neonicotinoid toxicity in birds are largely unknown. Thiamethoxam (TMX), as a representative neonicotinoid insecticide, is now widely detected in most environmental medium and animal bodies. In this study, 5 mg/kg body weight TMX (potential environmental intake level) were orally administrated to male Japanese quails (Coturnix japonica). We found a rapid absorption, distribution, metabolism and elimination of TMX in quails in a period of 24 h, with the main metabolite, clothianidin (CLO), being extensively distributed and rapidly eliminated from tissues as well. The maximum plasm concentration of CLO was consistent with wild birds. Metabolomics analysis and followed determination of liver enzymes mRNA expression indicated the rapid metabolism was mediated mainly by CYPs and GSTs that involved riboflavin metabolism and glutathione metabolism pathways upon TMX exposure. Molecular dynamic simulation showed the strongest binding interaction in quail CYP2H1-TMX and CYP3A12-CLO complexes among a set of CYPs-substrate. The present study elucidated toxicokinetic and underlying metabolic mechanisms of TMX in quails at environmentally-relevant concentration, the findings would facilitate the understanding of potential risks of TMX and its metabolites to birds.