Redox-dependent Cd2+ inhibition of BK-type Ca2+-activated K+ channels.

Large-conductance Ca2+-activated K+ channels (BK channels) are formed by Slo1 subunits as a homotetramer. Besides Ca2+, other divalent cations, such as Cd2+, also activate BK channels when applied intracellularly by shifting the conductance-voltage relation to more negative voltages. However, we found that if the inside-out patch containing BK channels was treated with solution containing reducing agents such as dithiothreitol (DTT), then subsequent Cd2+ application completely inhibited BK currents. The DTT-dependent Cd2+ inhibition could be reversed by treating the patch with solutions containing H2O2, suggesting that a redox reaction regulates the Cd2+ inhibition of BK channels. Similar DTT-dependent Cd2+ inhibition was also observed in a mutant BK channel, Core-MT, in which the cytosolic domain of the channel is deleted, and in the proton-activated Slo3 channels but not observed in the voltage-gated Shaker K+ channels. A possible mechanism for the DTT-dependent Cd2+ inhibition is that DTT treatment breaks one or more disulfide bonds between cysteine pairs in the BK channel protein and the freed thiol groups coordinate with Cd2+ to form an ion bridge that blocks the channel or locks the channel at the closed state. However, surprisingly, none of the mutations of all cysteine residues in Slo1 affect the DTT-dependent Cd2+ inhibition. These results are puzzling, with an apparent contradiction: on one hand, a redox reaction seems to regulate Cd2+ inhibition of the channel, but on the other hand, no cysteine residue in the Slo1 subunit seems to be involved in such inhibition.

Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects.

Cardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD), either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs (KCNQ1+KCNE1), a slowly activating K+ current, plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage-sensing domain (VSD) of the IKs channel. Here, we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed the drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Development of competitive and noncompetitive lateral flow immunoassays for pendimethalin using synthetic peptides.

Peptidomimetic and anti-immunocomplex peptides can be easily isolated from phage display libraries, and can be used as alternatives to chemical competing haptens to improve the sensitivity of small molecule immunoassay. In this work, 16 peptidomimetics and 7 anti-immunocomplex peptides of pendimethalin (PND) were obtained from cyclic 7-, 8-, 9-, and 10-residue peptide phage libraries. Peptidomimetic EJ-2 (CMFTGTDFPC) with the highest sensitivity in competitive phage enzyme-linked immunosorbent assay (ELISA) and immunocomplex peptide EF-30 (CNPGWPPIPC) with the highest sensitivity in noncompetitive phage ELISA were selected to prepare phage-free peptides with GGGSSK-biotin at the C-terminus. Competitive and noncompetitive lateral flow immunoassays (CLFIA and NLFIA) were developed by using the phage-free peptides. After optimization, the CLFIA and NLFIA showed visual limit of detections (vLODs) of 5 ng/mL and 2.5 ng/mL, respectively, which were improved two- and fourfold compared with a LFIA based on chemical hapten. The NLFIA showed better sensitivity than CLFIA in the detection of spiked samples, and can meet the detection requirements for agro-products regulated by EU and China. The detection results of CLFIA and NLFIA for blind samples were consistent with that of ultra performance liquid chromatography/tandem mass spectrometry.

Simultaneous determination of penthiopyrad enantiomers and its metabolite in vegetables, fruits, and cereals using ultra-high performance liquid chromatography-tandem mass spectrometry.

Penthiopyrad is a novel succinate dehydrogenase inhibitor that has one chiral center and exists a metabolite, 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide in its residue definition. An efficient analytical method for the simultaneous determination of penthiopyrad enantiomers and its metabolite in eight matrices were developed using modified quick, easy, cheap, effective, rugged, safe method, coupled with chiral stationary phase and ultra-high performance liquid chromatography-tandem mass spectrometry. The absolute configuration of penthiopyrad enantiomers was confirmed by polarimetry and electronic circular dichroism. Eight polysaccharide-based chiral stationary phases were evaluated in terms of the enantioseparation of penthiopyrad and separation-related factors (the mobile phase, flow rate and the column temperature) were optimized. To obtain an optimal purification, different sorbent combinations were assessed. The linearities of this method were acceptable in the range of 0.005 to 1 mg/L with R2  > 0.998, while the limits of detection and quantification were 0.0015 mg/kg and 0.01 mg/kg for two enantiomers and its metabolite. The average recoveries of R-(-)-penthiopyrad, S-(+)-penthiopyrad and the metabolite ranged from 75.4 to 109.1, 69.5 to 112.8, and 70.0 to 108.5%, respectively. The intra-day and inter-day relative standard deviations were less than 18.8%. The analytical method was accurate and convenient, which can support their further research on stereoselective degradation, residual monitoring and risk assessment.

Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio).

The research on the enantioselective toxic effects of chiral pesticides on non-target aquatic organisms has attracted more and more attention. This study investigated the enantioselective toxic effects of mefentrifluconazole (MFZ) on acute toxicity, developmental toxicity, locomotor behaviors, and the mRNA relative expression levels of genes related to neurodevelopment and cardiac development in zebrafish embryos or larvae. The 96-h lethal concentration 50 (LC50 ) values (exposed to racemate and enantiomers of MFZ, that is, rac-MFZ/(-)-MFZ/(+)-MFZ) were 1.010, 1.552, and 0.753 mg/L for embryo, and 0.753, 1.187, and 0.553 mg/L for larvae. The rac-MFZ/(-)-MFZ/(+)-MFZ can affect the heart development of zebrafish embryos, accompanied by heart rate inhibition, yolk sac deformities, pericardial deformities, and down-regulation of genes related to cardiotoxicity in larvae in an enantioselective manner. Moreover, the rac-MFZ/(-)-MFZ/(+)-MFZ also can affect the neural development of zebrafish embryos, accompanied by autonomic movement inhibition, swimming speed and swimming distance abnormalities, and down-regulation of genes related to neurotoxicity in larvae in an enantioselective manner. For all toxicity endpoints, the effect of the (+)-MFZ to early-staged zebrafish were significantly greater than that of (-)-MFZ. These results will help distinguishing the difference of MFZ enantiomers to zebrafish, and provide scientific reference for improving the risk assessment of chiral pesticides MFZ.

Enantioselective bioaccumulation and toxicity of the novel chiral antifungal agrochemical penthiopyrad in zebrafish (Danio rerio).

Succinate dehydrogenase inhibitor (SDHI) fungicides has been extensively used in agricultural production, which are not easily degrade in the environment and have various toxic effects on aquatic organisms. However, the toxic effects information to non-target organisms were mostly at the racemate level, which were poorly understood at the enantiomers level. Thus, this study aimed to investigate the enantioselective bioaccumulation behavior and toxic effects of penthiopyrad in zebrafish. Significant enantioselective bioaccumulation was observed when exposed to penthiopyrad at two dose levels: S-(+)-penthiopyrad was preferentially accumulated. Moreover, S-(+)-penthiopyrad caused oxidative stress in zebrafish liver. The results of real-time RT-PCR analyses revealed that exposure to penthiopyrad also enantioselectivity interfered with the expression of mitochondrial respiratory complexes, mtDNA synthesis, lipid metabolism and apoptosis-related genes. S-(+)-penthiopyrad significantly decreased most of the expression of the above gene, which showed higher toxic effects. We inferred that the toxicity mechanism of penthiopyrad was caused by lipid metabolism disorder and mitochondrial dysfunction in zebrafish, and further leads to apoptosis even DNA damage. This study provides more accurate data to investigate the environmental impact of penthiopyrad at the enantiomer level.

Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and Its Potential Therapeutic Targets: Insights from Modeling.

Gain-of-function mutations in the pore-forming subunit of IKs channels, KCNQ1, lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant IKs channels cause SQTS and the possibility of IKs-specific pharmacological treatment remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect on IKs gating properties and changes in the action potentials (AP) of human ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes with and without ß-adrenergic stimulation. V141M KCNQ1 caused a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to IKs accumulation. V141M KCNQ1 also caused a leftward shift of the conductance-voltage curve compared to wild type (WT) IKs (V1/2 = 33.6 ± 4.0 mV for WT, and 24.0 ± 1.3 mV for heterozygous V141M). A Markov model of heterozygous V141M mutant IKs was developed and incorporated into the O'Hara-Rudy model. Compared to the WT, AP simulations demonstrated marked rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M AP simulations, especially under ß-adrenergic stimulation. Computational simulations identified specific IK1 blockade as a beneficial pharmacologic target for reducing the transmural APD heterogeneity associated with V141M KCNQ1 mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural APD heterogeneity under ß-adrenergic stimulation. Computational simulations identified IK1 blockers as a potential antiarrhythmic drug of choice for SQTS.

Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening.

Voltage-gated ion channels generate dynamic ionic currents that are vital to the physiological functions of many tissues. These proteins contain separate voltage-sensing domains, which detect changes in transmembrane voltage, and pore domains, which conduct ions. Coupling of voltage sensing and pore opening is critical to the channel function and has been modeled as a protein-protein interaction between the two domains. Here, we show that coupling in Kv7.1 channels requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We found that voltage-sensing domain activation failed to open the pore in the absence of PIP2. This result is due to loss of coupling because PIP2 was also required for pore opening to affect voltage-sensing domain activation. We identified a critical site for PIP2-dependent coupling at the interface between the voltage-sensing domain and the pore domain. This site is actually a conserved lipid-binding site among different K(+) channels, suggesting that lipids play an important role in coupling in many ion channels.

A charged residue in S4 regulates coupling among the activation gate, voltage, and Ca2+ sensors in BK channels.

Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. One difficulty in studying sensor-gate coupling is to distinguish whether a structural perturbation alters the function of the sensor, the gate, or their coupling. BK channels are activated by membrane voltage and intracellular Ca(2+) via allosteric mechanisms with coupling among the activation gate and sensors quantitatively defined, providing an excellent model system for studying sensor-gate coupling. By studying BK channels expressed in Xenopus oocytes, here we show that mutation E219R in S4 alters channel function by two independent mechanisms: one is to change voltage sensor activation, shifting voltage dependence, and increase valence of gating charge movements; the other is to regulate coupling among the activation gate, voltage sensor, and Ca(2+) binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca(2+) sensitivity. These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels.

Biodegradation of nicosulfuron by a novel Alcaligenes faecalis strain ZWS11.

A bacterial strain ZWS11 was isolated from sulfonylurea herbicide-contaminated farmland soil and identified as a potential nicosulfuron-degrading bacterium. Based on morphological and physicochemical characterization of the bacterium and phylogenetic analysis of the 16S rRNA sequence, strain ZWS11 was identified as Alcaligenes faecalis. The effects of the initial concentration of nicosulfuron, inoculation volume, and medium pH on degradation of nicosulfuron were investigated. Strain ZWS11 could degrade 80.56% of the initial nicosulfuron supplemented at 500.0mg/L under the conditions of pH7.0, 180r/min and 30°C after incubation for 6days. Strain ZWS11 was also capable of degrading rimsulfuron, tribenuron-methyl and thifensulfuron-methyl. Four metabolites from biodegradation of nicosulfuron were identified, which were 2-aminosulfonyl-N, N-dimethylnicotinamide (M1), 4, 6-dihydroxypyrimidine (M2), 2-amino-4, 6-dimethoxypyrimidine (M3) and 2-(1-(4,6-dimethoxy-pyrimidin-2-yl)-ureido)-N,N-dimethyl-nicotinamide (M4). Among the metabolites detected, M2 was reported for the first time. Possible biodegradation pathways of nicosulfuron by strain ZWS11 were proposed. The degradation proceeded mainly via cleavage of the sulfonylurea bridge, O-dealkylation, and contraction of the sulfonylurea bridge by elimination of a sulfur dioxide group. The results provide valuable information for degradation of nicosulfuron in contaminated environments.

The combined neurotoxicity of DBP and nano-TiO2 in embryonic zebrafish (Danio rerio) revealed by oxidative activity, neuro-development genes expression and metabolomics changes.

Dibutyl phthalate (DBP) is a commonly used plasticizer that is frequently detected in water samples due to its widespread use. Titanium dioxide nanoparticles (n-TiO2) have been found to enhance the harmful effects of organic contaminants by increasing their bioavailability in aquatic environments. However, the combined toxic effects of DBP and n-TiO2 on aquatic organisms remain unclear. This study aimed to investigate the neurotoxicity of DBP and n-TiO2 synergistic exposure during the early life stage of zebrafish. The results of the study revealed that co-exposure of DBP and n-TiO2 led to an increase in deformities and a significant reduction in the active duration of zebrafish larvae. Furthermore, the co-exposure of DBP and n-TiO2 resulted in elevated levels of oxidative stress and altered gene expression related to neurodevelopment and apoptosis. Notably, n-TiO2 exacerbated the oxidative damage and apoptosis induced by DBP alone exposure. Additionally, co-exposure of the 1.0 mg/L DBP and n-TiO2 significantly affected the expression of genes associated with neurodevelopment. Moreover, disturbances in amino acid metabolism and interference with lipid metabolism were observed as a result of DBP and n-TiO2 co-exposure. In general, n-TiO2 aggravated the neurotoxicity of DBP in the early life stage of zebrafish by increasing oxidative stress, apoptosis, and disrupting amino acid synthesis and lipid metabolism. Therefore, it is essential to consider the potential risks caused by DBP and nanomaterials co-existence in the aquatic environment.

Comparative study of the effects of different surface-coated silver nanoparticles on thyroid disruption and bioaccumulation in zebrafish early life.

The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 µg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28-2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.

Effects of single and combined exposure of virgin or aged polyethylene microplastics and penthiopyrad on zebrafish (Danio rerio).

The interaction between pesticides and microplastics (MPs) can lead to changes in their mode of action and biological toxicity, creating substantial uncertainty in risk assessments. Succinate dehydrogenase inhibitor (SDHI) fungicides, a common fungicide type, are widely used. However, little is known about how penthiopyrad (PTH), a member of the SDHI fungicide group, interacts with polyethylene microplastics (PE-MPs). This study primarily investigates the individual and combined effects of virgin or aged PE-MPs and penthiopyrad on zebrafish (Danio rerio), including acute toxicity, bioaccumulation, tissue pathology, enzyme activities, gut microbiota, and gene expression. Short-term exposure revealed that PE-MPs enhance the acute toxicity of penthiopyrad. Long-term exposure demonstrated that PE-MPs, to some extent, enhance the accumulation of penthiopyrad in zebrafish, leading to increased oxidative stress injury in their intestines by the 7th day. Furthermore, exposure to penthiopyrad and/or PE-MPs did not result in histopathological damage to intestinal tissue but altered the gut flora at the phylum level. Regarding gene transcription, penthiopyrad exposure significantly modified the expression of pro-inflammatory genes in the zebrafish gut, with these effects being mitigated when VPE or APE was introduced. These findings offer a novel perspective on environmental behavior and underscore the importance of assessing the combined toxicity of PE-MPs and fungicides on organisms.

Translocation and dissipation of thiamethoxam applied by root irrigation in tomato plant-soil system.

Thiamethoxam (TMX) has been registered for use on a wide range of crops due to its versatile application methods, however, there is limited literature evaluating the residue behaviors of TMX applied through root irrigation. In this study, the uptake and translocation of TMX, its degradation to clothianidin (CLO), and dissipation in the tomato plant-soil system were conducted. TMX applied by root irrigation was transferable within the tomato plant, including stems, leaves, and fruits at different heights. TMX concentrations in the four sections of stems were ordered as Clower > Cmid > Cupper > Ctop, while in the leaves were ordered as Ctop > Cupper > Cmid > Clower. The degradation product CLO was detected in the tomato plant, and concentrations of CLO were even higher than those of TMX in the leaves. The translocation factor (TF) of TMX in the same section generally followed the order of TFleaf > TFstem > TFfruit. Residues of TMX and CLO in tomato on 7 days after application were below maximum residue limits (MRLs) in China and Codex Alimentarius Commission (CAC). This study promotes the evaluation of TMX applied through root irrigation for use in the tomato system from a dietary safety perspective.

Enantioselective toxic effects of the novel chiral antifungal agrochemical penthiopyrad in the early life stage of zebrafish (Danio rerio).

Penthiopyrad was extensively applied in agricultural production, however, the toxicities information of the penthiopyrad enantiomers on early life stages of aquatic organism were limited. This study investigated the enantioselective toxicity of penthiopyrad on the early life stage of zebrafish by acute toxicity, sublethal toxic effects and the mRNA relative expression levels of genes related to succinate dehydrogenase, cardiac development, and lipid metabolism. The results showed that the 96-h-LC50 of penthiopyrad racemate and enantiomers to zebrafish embryos were Rac-: 2.784 mg/L; R-(-)-: 3.528 mg/L; S-(+)-: 1.882 mg/L. Penthiopyrad exposure induced autonomous movement abnormalities, slowed heart rate and delayed hatching in zebrafish embryos, and caused developmental toxic effects such as pericardial edema and yolk sac edema. The mRNA relative expression levels results showed that penthiopyrad exposure induced significant enantioselectivity effect for the expression of the Sdha, Pr1 and Nkx2.5 with a 1.94-4.98-fold difference between different enantiomers, and significantly affected succinate dehydrogenase (energy metabolism), lipid metabolism and cardiac development-related genes expression. In general, S-(+)-penthiopyrad induced higher toxic effects in zebrafish embryos, and mitochondrial dysfunction may be an important cause of abnormal development. This study contributed to improve the comprehensive risk assessment and enantiomeric research system of penthiopyrad to early life stage of zebrafish.

Single and combined effects of polyethylene microplastics and acetochlor on accumulation and intestinal toxicity of zebrafish (Danio rerio).

The co-exposure of microplastics (MPs) and other contaminants has aroused extensive attention, but the combined impacts of MPs and pesticides remain poorly understood. Acetochlor (ACT), a widely used chloroacetamide herbicide, has raised concerns for its potential bio-adverse effects. This study evaluated the influences of polyethylene microplastics (PE-MPs) for acute toxicity, bioaccumulation, and intestinal toxicity in zebrafish to ACT. We found that PE-MPs significantly enhanced ACT acute toxicity. Also, PE-MPs increased the accumulation of ACT in zebrafish and aggravate the oxidative stress damage of ACT in intestines. Exposure to PE-MPs or/and ACT causes mild damage to the gut tissue of zebrafish and altered gut microbial composition. In terms of gene transcription, ACT exposure triggered a significant increase in inflammatory response-related gene expressions in the intestines, while some pro-inflammatory factors were found to be inhibited by PE-MPs. This study provides a new perspective on the fate of MPs in the environment and on the assessment of the combined effects of MPs and pesticides on organisms.

Multi-walled carbon nanotubes enhance the toxicity effects of dibutyl phthalate on early life stages of zebrafish (Danio rerio): Research in physiological, biochemical and molecular aspects.

Phthalate esters (PAEs) are widely used as plasticizers. PAEs are ubiquitous in natural water bodies, with dibutyl phthalate (DBP) being one of the most common PAEs. DBP is prone to leaching or migration into the environment, posing serious health and environmental risks. Carbon nanotubes (CNTs) have been widely used in various fields with the rapid development of nanotechnology. CNTs could alter the environmental behavior and toxicity of co-existing pollutants. CNTs have been shown to rapidly adsorb PEAs. However, current knowledge about the effects of CNTs on DBP toxicity is limited. Here we show that the toxic effects of single and combined exposure to DBP (0.1, 0.5, 1.0 mg/L) and different CNTs (MWCNTs/MWCNTs-COOH, 0.5 mg/L) on the early growth stage of zebrafish. The results suggested that a significant increase in heart rate and heart malformation rate was observed after co-exposure of DBP and MWCNTs/MWCNTs-COOH (p < 0.05). Furthermore, combined exposure increased antioxidant enzyme activity during early developmental stages in zebrafish (p < 0.05). The qRT-PCR results revealed that DBP and MWCNTs/MWCNTs-COOH co-exposure significantly interfered with the expression of genes related to oxidative stress, energy metabolism, development of cardiac function, and apoptosis (p < 0.05). In addition, for oxidative stress and cardiotoxicity, MWCNTs/MWCNTs-COOH aggravated the toxic effects of 0.5 mg/L DBP on embryos/larvae. The metabolomics results showed that co-exposure mitigated the disturbance of amino acid metabolism mediated by single DBP exposure. In general, MWCNTs/MWCNTs-COOH increased the impact of DBP in the early developmental stages of zebrafish. This study provides new insights into the toxicology of early developmental stages of aquatic organisms exposed to co-exist pollutants of DBP and CNTs.

A Drosophila heart optical coherence microscopy dataset for automatic video segmentation.

The heart of the fruit fly, Drosophila melanogaster, is a particularly suitable model for cardiac studies. Optical coherence microscopy (OCM) captures in vivo cross-sectional videos of the beating Drosophila heart for cardiac function quantification. To analyze those large-size multi-frame OCM recordings, human labelling has been employed, leading to low efficiency and poor reproducibility. Here, we introduce a robust and accurate automated Drosophila heart segmentation algorithm, called FlyNet 2.0+, which utilizes a long short-term memory (LSTM) convolutional neural network to leverage time series information in the videos, ensuring consistent, high-quality segmentation. We present a dataset of 213 Drosophila heart videos, equivalent to 604,000 cross-sectional images, containing all developmental stages and a wide range of beating patterns, including faster and slower than normal beating, arrhythmic beating, and periods of heart stop to capture these heart dynamics. Each video contains a corresponding ground truth mask. We expect this unique large dataset of the beating Drosophila heart in vivo will enable new deep learning approaches to efficiently characterize heart function to advance cardiac research.

Enantioselective degradation of indoxacarb in cabbage and soil under field conditions.

The enantioselective degradation of indoxacarb in cabbage and soil has been investigated in Beijing and Anhui under open conditions. Indoxacarb enantiomers in samples were extracted with acetonitrile, cleaned up by florisil SPE column, separated on high performance liquid chromatography with a cellulose-tris-(3, 5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP), and determined by a photodiode array detector. The validation of the developed method by fortification rac-indoxcarb in cabbage and soil showed good accuracy and precision. The results of field trials indicated that the dissipation of indoxacarb enantiomers followed pseudo-first-order kinetics or first-order kinetics in cabbage and soil at two locations. The half-lives of two enantiomers in cabbage ranged from 2.8 to 4.6 d which were shorter than those in soil ranging from 23 to 35 d. The changes of enantiomeric fraction values proved that enantioselective degradation of indoxacarb happened in cabbage and soil. The (-)-indoxacarb showed faster degradation in the Beijing cabbage, whereas in the Anhui cabbage, (+)-indoxacarb preferentially degraded. In soil, preferential degradation of (+)-indoxacarb was observed at two locations.