Rapid Response of Daphnia magna Motor Behavior to Mercury Chloride Toxicity Based on Target Tracking.

A rapid and timely response to the impacts of mercury chloride, which is indispensable to the chemical industry, on aquatic organisms is of great significance. Here, we investigated whether the YOLOX (improvements to the YOLO series, forming a new high-performance detector) observation system can be used for the rapid detection of the response of Daphnia magna targets to mercury chloride stress. Thus, we used this system for the real-time tracking and observation of the multidimensional motional behavior of D. magna. The results obtained showed that the average velocity (v¯), average acceleration (a¯), and cumulative travel (L) values of D. magna exposed to mercury chloride stress changed significantly under different exposure times and concentrations. Further, we observed that v¯, a¯ and L values of D. magna could be used as indexes of toxicity response. Analysis also showed evident D. magna inhibition at exposure concentrations of 0.08 and 0.02 mg/L after exposure for 10 and 25 min, respectively. However, under 0.06 and 0.04 mg/L toxic stress, v¯ and L showed faster toxic response than a¯, and overall, v¯ was identified as the most sensitive index for the rapid detection of D. magna response to toxicity stress. Therefore, we provide a strategy for tracking the motile behavior of D. magna in response to toxic stress and lay the foundations for the comprehensive screening of toxicity in water based on motile behavior.

Highly sensitive response to the toxicity of environmental chemicals in transparent casper zebrafish.

The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfaw2/w2;mpv17a9/a9), a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC50) values of these chemicals in casper embryos were 62-87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67-77 % in relative to the wild-type, and the half-maximal effective concentration (EC50) in casper was 73 % of that in the wild-type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild-type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper.

[Source Appointment and Assessment of Heavy Metal Pollution in Surface Dust in the Main District Bus Stops of Tianshui City].

In this study, a PMF model was used to identify the sources and pollution level of heavy metals in the surface dust of a bus station. On the basis of the traditional heavy metal pollution evaluation methods, the Hakanson toxicity response coefficient was used to modify the traditional weight. The matter-element extension theory was introduced to reflect the toxicological properties and hazard degree of the heavy metals, and the matter-element extension model was established to evaluate the pollution level of heavy metals in the surface dust of the study area. The results were compared with Igeo, PN, and RI. ① Except for Co and V, the other heavy metals were higher than the Gansu soil background values by 1.29-9.30 times. The points of Cu and Pb exceeded the rate by 100%, and Cr, Ni, and As exceeded the rate by 96.15%, 94.23%, and 96.15%, respectively. ② PMF showed that source 1 was a natural source, and its contribution rate to V was 32.12%. Source 2 was natural-traffic pollution sources, contributing 51.50% and 33.37% to Cu and Co, respectively. Source 3 was a construction waste pollution source, with contribution rates of 45.06% and 44.70% for Cr and Ni, respectively, and source 4 was a coal-traffic mixed source, with contribution rates of 49.89% and 75.25% for As and Pb, respectively. ③ The matter-element evaluation results showed that the surface dust of the bus stops was mainly class IV (moderately polluted), and 13% of sample points were still clean, 37% were moderately polluted, and 25% were slightly and heavily polluted. The results of this method were quite different from the PN results and were more consistent with the RI results, indicating that its evaluation results were more sensitive and can be used for heavy metal pollution assessment.

Toxicity warning and online monitoring of disinfection by-products in water by electroautotrophic biocathode sensors.

As a result of the 2019 coronavirus pandemic, disinfection byproducts generated by the extensive use of chlorine disinfectants have infiltrated the aquatic environment, severely threatening ecological safety and human health. Therefore, the accurate monitoring of the biotoxicity of aqueous environments has become an important issue. Biocathode sensors are excellent choices for toxicity monitoring because of their special electroautotrophic respiration functions. Herein, a novel electroautotrophic biosensor with rapid, sensitive, and stable response and quantifiable output was developed. Its toxicity response was tested with typical disinfection byproducts dichloromethane, trichloromethane, and combinations of both, and corresponding characterization models were developed. Repeated toxicity tests demonstrated that the sensor was reusable rather being than a disposable consumable, which is a prerequisite for its long-term and stable operation. Microbial viability confirmed a decrease in sensor sensitivity due to microbial stress feedback to the toxicants, which is expected to be calibrated in the future by the standardization of the biofilms. Community structure analysis indicated that Moheibacter and Nitrospiraceae played an important role in the toxic response to chlorine disinfection byproducts. Our research provides technical support for protecting the environment and safeguarding water safety for human consumption and contributes new concepts for the development of novel electrochemical sensors.

Subcellular-Level Mitochondrial Energy Metabolism Response in the Fat Body of the German Cockroach Fed Abamectin.

Mitochondria are the leading organelle for energy metabolism. The toxic effects of environmental toxicants on mitochondrial morphology, energy metabolism, and their determination of cell fate have already been broadly studied. However, minimal research exists on effects of environmental toxicants such as pesticides on mitochondrial energy metabolism at in vitro subcellular level, particularly from an omics perspectives (e.g., metabolomics). Here, German cockroach (Blattella germanica) was fed diets with (0.01 and 0.001 mg/mL) and without abamectin, and highly purified fat body mitochondria were isolated. Swelling measurement confirmed abnormal mitochondrial swelling caused by abamectin stress. The activity of two key mitochondrial energy metabolism-related enzymes, namely succinic dehydrogenase and isocitrate dehydrogenase, was significantly affected. The metabolomic responses of the isolated mitochondria to abamectin were analyzed via untargeted liquid chromatography/mass spectrometry metabolomics technology. Fifty-two differential metabolites (DMs) were identified in the mitochondria between the 0.001 mg/mL abamectin-fed and the control groups. Many of these DMs were significantly enriched in pathways involved in ATP production and energy consumption (e.g., oxidative phosphorylation, TCA cycle, and pentose phosphate pathway). Nineteen of the DMs were typically related to energy metabolism. This study is valuable for further understanding mitochondrial toxicology under environmental toxicants, particularly its subcellular level.

Life History of Chrysodeixis includens (Lepidoptera: Noctuidae) on Positively Charged Zein Nanoparticles.

Research indicates that nanoparticles can be an effective agricultural pest management tool, though unintended effects on the insect must be evaluated before their use in agroecosystems. Chrysodeixis includens (Walker) was used as a model to evaluate chronic parental and generational exposure to empty, positively charged zein nanoparticles ((+)ZNP) and methoxyfenozide-loaded zein nanoparticles (+)ZNP(MFZ) at low-lethal concentrations. To determine concentration limits, an acute toxic response test on meridic diet evaluated (+)ZNP(MFZ) and technical grade methoxyfenozide using two diet assay techniques. No differences in acute toxicity were observed between the two treatments within their respective bioassays. With these results, population dynamics following chronic exposure to low-lethal concentrations were evaluated. Parental lifetables evaluated cohorts of C. includens reared on diet treated with LC5 equivalents of (+)ZNP, (+)ZNP(MFZ), or technical grade methoxyfenozide. Compared to technical grade methoxyfenozide, (+)ZNP(MFZ) lowered both the net reproductive rate and intrinsic rate of increase, and was more deleterious to C. includens throughout its lifespan. This was contrasted to (+)ZNP, which showed no differences in population dynamics when compared with the control. To evaluate chronic exposure to (+)ZNP, generational lifetables reared cohorts of C. includens on LC5 equivalent values of (+)ZNP and then took the resulting offspring to be reared on either (+)ZNP or untreated diet. No differences in lifetable statistics were observed between the two treatments, suggesting that (+)ZNP at low ppm do not induce toxic generational effects. This study provides evidence into the effects of nanodelivered methoxyfenozide and the generational impact of (+)ZNP.

[Using the Matter-Element Extension Model to Assess Heavy Metal Pollution in Topsoil in Parks in the Main District Park of Lanzhou City].

The UNMIX model was used to analyze the source of heavy metals found to be present in the topsoil of parks in the main district of Lanzhou City. The Hakanson toxicity response coefficient was used concurrently to modify the traditional weights in the model, and the matter-element extension model was used to evaluate heavy metal pollution. The results of the evaluation were compared with the comprehensive pollution index (PN) and potential ecological risk index (RI). The results were as follows. ①The average heavy metal content in the topsoil at each sampling point was higher than that of the background value of soil in Lanzhou, with the proportion of Ni, Cu, and Co being 100% while the proportion of Cr, V, Pb, and As contents were 58.82%, 14.71%, 20.59%, and 2.94%, respectively. ② The results of source analysis showed that there were three major sources of heavy metal pollution in the topsoil of the parks in the study area. Source 1 is construction pollution, which contributes 56% of the Co present. Source 2 is traffic pollution, which contributes 44% and 52% of Cu and Pb, respectively. Source 3 is natural, and contributes 62%, 60%, 56%, and 56% of V, Cr, Ni, and As, respectively. Thus, this research showed that natural sources are predominant. ③ The weight correction effect for each heavy metal was significant; there was an approximately 44% reduction in both Cr and V, while the corrected weights of Ni, Cu, Pb, As, and Co increased in the order Co < Pb < Cu < Ni < As compared with the conventional weights. The most obvious change in weight was that of As, which increased by approximately 188%. ④ The results of the evaluation using the matter-element model showed that the state of 46% of the topsoil in the parks in the study area was grade Ⅴ (severely polluted), while 41% was grade Ⅳ (moderately polluted) and 3% was grade Ⅲ (lightly polluted); Co was the main pollutant. The results of the model evaluation were roughly the same as of from the PN and RI, indicating that the matter-element extension model can be used to evaluate heavy metal pollution in soil and the evaluation results are accurate and objective.

Functional analysis of a gene-edited mouse model to gain insights into the disease mechanisms of a titin missense variant.

Titin truncating variants are a well-established cause of cardiomyopathy; however, the role of titin missense variants is less well understood. Here we describe the generation of a mouse model to investigate the underlying disease mechanism of a previously reported titin A178D missense variant identified in a family with non-compaction and dilated cardiomyopathy. Heterozygous and homozygous mice carrying the titin A178D missense variant were characterised in vivo by echocardiography. Heterozygous mice had no detectable phenotype at any time point investigated (up to 1 year). By contrast, homozygous mice developed dilated cardiomyopathy from 3 months. Chronic adrenergic stimulation aggravated the phenotype. Targeted transcript profiling revealed induction of the foetal gene programme and hypertrophic signalling pathways in homozygous mice, and these were confirmed at the protein level. Unsupervised proteomics identified downregulation of telethonin and four-and-a-half LIM domain 2, as well as the upregulation of heat shock proteins and myeloid leukaemia factor 1. Loss of telethonin from the cardiac Z-disc was accompanied by proteasomal degradation; however, unfolded telethonin accumulated in the cytoplasm, leading to a proteo-toxic response in the mice.We show that the titin A178D missense variant is pathogenic in homozygous mice, resulting in cardiomyopathy. We also provide evidence of the disease mechanism: because the titin A178D variant abolishes binding of telethonin, this leads to its abnormal cytoplasmic accumulation. Subsequent degradation of telethonin by the proteasome results in proteasomal overload, and activation of a proteo-toxic response. The latter appears to be a driving factor for the cardiomyopathy observed in the mouse model.

A new method for estimating sedimental integrated toxicity of heavy metal mixtures to aquatic biota: a case study.

The existing methods of measuring combined toxicity of heavy metal mixtures in environment do not fully consider three major factors (i.e., number of heavy metal species, aquatic biota, all investigated sites as an entity). Herein, a new method named joint probabilistic risk (JPR) method is proposed for evaluating the combined toxicity of heavy metal mixtures to aquatic biota. In this new method, the above three factors are fully taken into account. In order to evaluate the feasibility of the new method, the Pearl River Estuary (PRE) is selected as a case study. Concentrations of heavy metals (Cd, Pb, Cr, Ni, Cu, and Zn) in surface sediments of PRE are investigated and toxic equivalent factors (TEFs) of these heavy metals are calculated. Based on TEFs, sedimental concentrations of heavy metals of PRE are converted to Cd toxic equivalent concentration (Cdeq), while the Cd toxicity data (Cdto) are extracted from the literature. The probability density curves for Cdeq and Cdto are constructed and the overlap area is quantified as 0.2497. This indicates that the surface sediments of PRE have a 24.97% probability of toxic effect towards aquatic biota. Finally, this new method is validated by two indirect methods of mERMq and mPELq.

Comparative acute toxicity of glyphosate-based herbicide (GBH) to Daphnia magna, Tisbe longicornis, and Emerita analoga.

The aim of this work was to know the differential composition of the dissolved fraction of a glyphosate-based herbicide (GBH), commercialized as GLIFOPAC, when reaches different aquatic environments and its ecotoxicological effects on crustaceans species living in them. Daphnia magna, Tisbe longicornis, and Emerita analoga were exposed to glyphosate herbicide called GLIFOPAC (480 g L-1 of active ingredient or a.i.) at concentrations between 0.5 and 4.8 g a.i. L-1. Acute toxicity in D. magna (48 h-LC50), E. analoga (48 h-LC50), and T. longicornis (96 h-LC50) was studied. Chromatographic analysis of the GBH composition used and water (freshwater/sea water) polluted with GLIFOPAC were evaluated. Results reported acute toxicity (48-96 h-LC50) values for D. magna, E. analoga and T. longicornis of 27.4 mg L-1, 806.4 mg L-1, and 19.4 mg L-1, respectively. Chromatographic evaluation described around 45 substances of the GLIFOPAC composition, such as from the surfactant structures (aliphatic chain with esther/ether group), metabolites (AMPA), and other substances (glucofuranose, glucopyranoside, galactopyranose). This study evidenced differences in the GLIFOPAC composition in freshwater and marine water, which may differentiate the toxic response at the crustacean-level in each aquatic environment.

Pollution characteristics and ecological risk assessment of 11 unheeded metals in sediments of the Chinese Xiangjiang River.

With the change in global climate and environment, water scarcity has been of great concern around the word and exacerbated by serious pollution in water resources. Pollutants accumulated in sediments are threatening water safety and ecological security. Different from others focusing on prevalent heavy metals (Cu, Pb, Zn, As, Cd, Cr, Hg, etc.), in this study, some unheeded metal pollutants Tl, Sb, Mo, Sr, Co, V, Ti, Ca, Mg, Be and Li were monitored in sediments of the Xiangjiang River, China. It was found that there was no remarkable vertical variation with depth, but the seasonal characteristics of Tl, Sb, Mo, Be and Li. The enrichment, pollution and potential ecological risk of Tl, Sb and Mo were revealed by the enrichment factor (EF), geoaccumulation index (Igeo), pollution load index (PLIsite and PLIzone) and potential ecological risk index (RI). It is noticed that the pollution of Tl mainly occurred in summer at midstream and downstream and Mo pollution was much higher than Sb in summer and the reverse in other seasons. Additionally, sediment quality on east side was worse than on west side in Songbai section of the Xiangjiang River. For the first time, the toxic-response factor was figured out as Mo = 18, Tl = 17, Sb = 13, Sr = 6, Co = Be = 1, V = Li = 0, and importantly, the high potential ecological risk of Tl, Sb and Mo needs to be taken seriously for the comprehensive assessment on watershed environmental quality.

Immunotoxicity in green mussels under perfluoroalkyl substance (PFAS) exposure: Reversible response and response model development.

The immunotoxicity of 4 commonly detected perfluoroalkyl substances (PFASs), namely, perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) was investigated by measuring biomarkers of the immune profile of green mussels, Perna viridis. The biomarkers included neutral red retention, phagocytosis, and spontaneous cytotoxicity, all of which were tested on mussel hemocytes. Hemocytes are an important component of the invertebrate immune system. We found that exposure to PFASs could lead to reduced hemocyte cell viability and suppress immune function by up to 50% of normal performance within the experimental exposure range. The results indicate that PFASs have an immunotoxic potential and thus could pose severe health risks to aquatic organisms. The reported immunotoxicity is likely to result from the compounds' direct and indirect interactions with the hemocyte membrane, and therefore likely to affect the functionality of these cells. The immunotoxic response was found to be related to the organism's burden of PFASs, and was reversible when the compounds were removed from the test organisms. Based on this relationship, models using an organism's PFAS concentration and bioaccumulation factor (BAF) as the independent variables were established to quantify PFAS-induced immunotoxicity. The models help us to gain a better understanding of the toxic mechanism of PFASs, and provide a tool to evaluate adverse effects for the whole group of compounds with one mathematical equation. Environ Toxicol Chem 2018;37:1138-1145. © 2018 SETAC.

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1.

The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant. AFB1 toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB1, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB1 were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB1-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB1-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

Toxic responses of Sox2 gene in the regeneration of the earthworm Eisenia foetida exposed to Retnoic acid.

Exogenous retinoic acid delays and disturbs the regeneration of Eisenia foetida. The stem cell pluripotency factor, Sox2, can play a crucial role in cell reprogramming and dedifferentiation. In this study, we compared the regeneration of Eisenia foetida in different segments after amputation and the effects of retinoic acid on the regeneration of different segments. The results showed that the regeneration speed of the head and tail was slightly faster than the middle part, and retinoic acid disrupted and delayed the regeneration of the earthworm. The qRT-PCR and Western blot analysis showed that the expression of the Sox2 gene and Sox2 protein was highest on the seventh day in different segments (p<0.05). After treatment with retinoic acid, the expression level of the Sox2 gene and Sox2 protein was significantly reduced (p<0.05). The results indicated that the regeneration of earthworms and the formation of blastema are related to the expression of the Sox2 gene and protein. Retinoic acid delays and interferes with the regeneration of the earthworm by affecting the expression levels of the Sox2 gene and protein.

Toxic responses of microorganisms to nickel exposure in farmland soil in the presence of earthworm (Eisenia fetida).

Nickel (Ni)-contamination impairs soil ecosystem, threatening human health. A laboratory simulation of Ni-polluted farmland soil study, in the presence or absence of earthworm, was carried out to investigate the toxic responses of soil microorganisms, including microbial biomass C (MBC), soil basal respiration (SBR), metabolic quotient (qCO2), urease (UA) and dehydrogenase activities (DHA). Additionally, the variations of Ni bioavailability were also explored. Results manifested that MBC and SBR were stimulated at 50 and 100 mg·kg-1 of Ni but inhibited by further increasing Ni level, showing a Hormesis effect. Earthworm input delayed the occurrence of a maximum SBR inhibition rate under the combined double-factors of time and dose. No specific effect of Ni concentration on the qCO2 was observed. UA was significantly suppressed at 800 mg·kg-1 Ni (P < 0.05 or 0.01), whereas DHA was more sensitive and significantly inhibited throughout all the treatments (P < 0.01), indicating a pronounced dose-response relationship. The addition of earthworm facilitated all the biomarkers above. The time-dependent of dose-effect relationship (TDR) on MBC and SBR inhibition rates suggested that the peak responsiveness of microorganisms to Ni stress were approximate on the 21st day. The bioavailable form of per unit Ni concentration declined with time expanded and concentration increased, and the changeable process of the relative amount of bioavailability was mainly controlled by a physicochemical reactions.

Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles.

The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS) may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS) (with depression) and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR) produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

Glutaraldehyde treatment elicits toxic response compared to decellularization in bovine pericardium.

Glutaraldehyde-stabilized bovine pericardium is used for clinical application since 1970s because of its desirable features such as less immunogenicity and acceptable durability. However, a propensity for calcification is reported on account of glutaraldehyde treatment. In this study, commercially available glutaraldehyde cross-linked bovine pericardium was evaluated for its in vitro cytotoxic effect, macrophage activation, and in vivo toxic response in comparison to decellularized bovine pericardium. Glutaraldehyde-treated bovine pericardium and its extract were observed to be cytotoxic and it also caused significant inflammatory cytokine release from activated macrophages. Significant antibody response, calcification response, necrotic, and inflammatory response were noticed in glutaraldehyde-treated bovine pericardium in comparison to decellularized bovine pericardium in a rat subcutaneous implantation model. Glutaraldehyde-treated bovine pericardium also failed in acute systemic toxicity testing and intracutaneous irritation testing as per ISO 10993. With respect to healing and implant remodeling, total lack of host tissue incorporation and angiogenesis was noticed in glutaraldehyde-treated bovine pericardium compared to excellent host fibroblast incorporation and angiogenesis within the implant in decellularized bovine pericardium. In conclusion, using in vitro and in vivo techniques, this study has demonstrated that glutaraldehyde-treated bovine pericardium elicits toxic response compared to decellularized bovine pericardium which is not congenial for long-term implant performance.