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• Sb(III) oxidation was mediated by AQDS and phenolic. • · OH, O 2 −• and SQ−• were found as dominant free radicals intermediates. • Oxidation was accelerated by free radical catalysis and electron transfer. • H 2 O 2 was dominant oxidant for Sb(III) oxidation in metabolites. • The secondary mineral mopungite formation sequesters part of Sb(V). Microbial oxidation and the mechanism of Sb(III) are key governing elements in biogeochemical cycling. A novel Sb oxidizing bacterium, Klebsiella aerogenes HC10, was attracted early and revealed that extracellular metabolites were the main fractions driving Sb oxidation. However, linkages between the extracellular metabolite driven Sb oxidation process and mechanism remain elusive. Here, model phenolic and quinone compounds, i.e., anthraquinone-2,6-disulfonate (AQDS) and hydroquinone (HYD), representing extracellular oxidants secreted by K. aerogenes HC10, were chosen to further study the Sb(III) oxidation mechanism. N 2 purging and free radical quenching showed that oxygen-induced oxidation accounted for 36.78% of Sb(III) in the metabolite reaction system, while hydroxyl free radicals (· OH) accounted for 15.52%. · OH and H 2 O 2 are the main driving factors for Sb oxidation. Radical quenching, methanol purification and electron paramagnetic resonance (EPR) analysis revealed that · OH, superoxide radical (O 2 •−) and semiquinone (SQ−•) were reactive intermediates of the phenolic induced oxidation process. Phenolic-induced ROS are one of the main oxidants in metabolites. Cyclic voltammetry (CV) showed that electron transfer of quinone also mediated Sb(III) oxidation. Part of Sb(V) was scavenged by the formation of the secondary Sb(V)-bearing mineral mopungite [NaSb(OH) 6 ] in the incubation system. Our study demonstrates the microbial role of oxidation detoxification and mineralization of Sb and provides scientific references for the biochemical remediation of Sb-contaminated soil. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug metabolism is one of the main processes governing the pharmacokinetics and toxicity of drugs via their chemical biotransformation and elimination. In humans, the liver, enriched with cytochrome P450 (CYP) enzymes, plays a major metabolic and detoxification role. The gut microbiome and its complex community of microorganisms can also contribute to some extent to drug metabolism. However, during an infection when pathogenic microorganisms invade the host, our knowledge of the impact on drug metabolism by this pathobiome remains limited. The intrinsic resistance mechanisms and rapid metabolic adaptation to new environments often allow the human bacterial pathogens to persist, despite the many antibiotic therapies available. Here, we demonstrate that a bacterial CYP enzyme, CYP107S1, from Pseudomonas aeruginosa, a predominant bacterial pathogen in cystic fibrosis patients, can metabolize multiple drugs from different classes. CYP107S1 demonstrated high substrate promiscuity and allosteric properties much like human hepatic CYP3A4. Our findings demonstrated binding and metabolism by the recombinant CYP107S1 of fluoroquinolone antibiotics (ciprofloxacin and fleroxacin), a cystic fibrosis transmembrane conductance regulator potentiator (ivacaftor), and a selective estrogen receptor modulator antimicrobial adjuvant (raloxifene). Our in vitro metabolism data were further corroborated by molecular docking of each drug to the heme active site using a CYP107S1 homology model. Our findings raise the potential for microbial pathogens modulating drug concentrations locally at the site of infection, if not systemically, via CYPmediated biotransformation reactions. To our knowledge, this is the first report of a CYP enzyme from a known bacterial pathogen that is capable of metabolizing clinically utilized drugs. [ABSTRACT FROM AUTHOR]

It is known that the recommended dietary allowance of selenium (Se) is dangerously close to its tolerable upper intake level. Se is detoxified and excreted in urine as trimethylselenonium ion (TMSe) when the amount ingested exceeds the nutritional level. Recently, we demonstrated that the production of TMSe requires two methyltransferases: thiopurine S-methyltransferase (TPMT) and indolethylamine N-methyl-transferase (INMT). In this study, we investigated the substrate recognition mechanisms of INMT and TPMT in the Se-methylation reaction. Examination of the Se-methyltransferase activities of two paralogs of INMT, namely, nicotinamide N-methyltransferase and phenylethanolamine N-methyltransferase, revealed that only INMT exhibited Se-methyltransferase activity. Consistently, molecular dynamics simulations demonstrated that dimethylselenide was preferentially associated with the active center of INMT. Using the fragment molecular orbital method, we identified hydrophobic residues involved in the binding of dimethylselenide to the active center of INMT. The INMT-L164R mutation resulted in a deficiency in Se- and N-methyltransferase activities. Similarly, TPMT-R152, which occupies the same position as INMT-L164, played a crucial role in the Se-methyltransferase activity of TPMT. Our findings suggest that TPMT recognizes negatively charged substrates, whereas INMT recognizes electrically neutral substrates in the hydrophobic active center embedded within the protein. These observations explain the sequential requirement of the two methyltransferases in producing TMSe. [ABSTRACT FROM AUTHOR]

Aminotransferases (ATs) catalyze pyridoxal 5'-phosphate-dependent transamination reactions between amino donor and keto acceptor substrates and play central roles in nitrogen metabolism of all organisms. ATs are involved in the biosynthesis and degradation of both proteinogenic and nonproteinogenic amino acids and also carry out a wide variety of functions in photorespiration, detoxification, and secondary metabolism. Despite the importance of ATs, their functionality is poorly understood as only a small fraction of putative ATs, predicted from DNA sequences, are associated with experimental data. Even for characterized ATs, the full spectrum of substrate specificity, among many potential substrates, has not been explored in most cases. This is largely due to the lack of suitable high-throughput assays that can screen for AT activity and specificity at scale. Here we present a new high-throughput platform for screening AT activity using bioconjugate chemistry and mass spectrometry imaging-based analysis. Detection of AT reaction products is achieved by forming an oxime linkage between the ketone groups of transaminated amino donors and a probe molecule that facilitates mass spectrometry-based analysis using nanostructure-initiator mass spectrometry or MALDI-mass spectrometry. As a proof-ofprinciple, we applied the newly established method and found that a previously uncharacterized Arabidopsis thaliana tryptophan AT-related protein 1 is a highly promiscuous enzyme that can utilize 13 amino acid donors and three keto acid acceptors. These results demonstrate that this oxime-mass spectrometry imaging AT assay enables highthroughput discovery and comprehensive characterization of AT enzymes, leading to an accurate understanding of the nitrogen metabolic network. [ABSTRACT FROM AUTHOR]

Exposure to the vinyl monomer acrylonitrile (AN) is primarily occupational. AN is also found in cigarette smoke. AN can be detoxified to form N -acetyl-S-(2-cyanoethyl)-cysteine (CEMA) or activated to 2-cyanoethylene oxide (CEO) and detoxified to form N -acetyl-S-(1-cyano-2-hydroxyethyl)-cysteine (CHEMA) and N -acetyl-S-(2-hydroxyethyl)-cysteine (HEMA). These urinary mercapturic acids (MAs) are considered to be potential biomarkers of AN exposure. This study assessed personal AN exposure, urinary MAs (CEMA, CHEMA, and HEMA), and cotinine (a biomarker of cigarette smoke) in 80 AN-exposed and 23 non-exposed factory workers from urine samples provided before and after work shifts. Unambiguous linear correlations were observed between levels of urinary CEMA and CHEMA with personal AN exposures, indicating their potential as chemically-specific biomarkers for AN exposures. AN exposure was the dominant factor in MA formation for AN-exposed workers, whereas urinary cotinine used as a biomarker showed that cigarette smoke exposure was the primary factor for non-exposed workers. The CHEMA/CEMA and (CHEMA+HEMA)/CEMA ratios in this human study differ from those in similar studies of AN-treated rats and mice in literature, suggesting a possible dose- and species-dependent effect in AN metabolic activation and detoxification. [Display omitted] • Systematic comparison of urinary CEMA, CHEMA, and HEMA between AN- and non-exposed workers. • Unambiguous linear correlation between urinary CEMA and CHEMA and personal AN exposures. • Revelation of CEMA and CHEMA as potential chemically-specific biomarkers for AN exposures. • Illustration of dose- and species-dependent in AN metabolic activation and detoxification. [ABSTRACT FROM AUTHOR]

Acrylamide is pervasive, and its exposure poses numerous health risks. This study examines both the direct and transgenerational effects of acrylamide toxicity in Caenorhabditis elegans , focusing on physiological and behavioral parameters. Parental exposure to acrylamide compromised several aspects of nematode health, including lifespan, reproductive capacity, body dimensions, and motor and sensory functions. Notably, while exposure to low concentrations of acrylamide did not alter the physiological traits of the offspring—except for their learning and memory—these findings suggest a possible adaptive response to low-level exposure that could be inherited by subsequent generations. Furthermore, continued acrylamide exposure in the offspring intensified both physiological and perceptual toxicity. Detailed analysis revealed dose-dependent alterations in acrylamide's detoxification and metabolic pathways. In particular, it inhibits the gene gst-4 , which encodes a crucial enzyme in detoxification, mitigates DNA damage induced by acrylamide, and highlights a potential therapeutic target to reduce its deleterious effects. Mechanism of acrylamide toxicity diagram. Exposure to acrylamide negatively affects growth, development, motor activity and sensory behavior of parental nematodes. When exposed to low concentrations of acrylamide, progeny nematodes maintain normal physiological status and lifespan, although sensory perception is affected. In contrast, higher concentrations of acrylamide adversely affect the physiological and sensory functional status of progeny nematodes. In addition, simultaneous exposure of parents and offspring to acrylamide exacerbated the harmful effects, especially on the physiological state and sensory memory behavior of the offspring. Furthermore, the acrylamide detoxification pathway is regulated with gst-4 playing an important role as a key gene. In particular, inhibition of the gst-4 gene, which encodes a key enzyme for detoxification, attenuates acrylamide-induced DNA damage and highlights a potential therapeutic target to reduce its deleterious effects. [Display omitted] • Acrylamide exposure impairs nematode physiology and motility. • Acrylamide exposure impairs nematode sensory behavior and learning memory. • Parental exposure to acrylamide impairs perceptual learning behavior in offspring. • Toxicity to nematodes is exacerbated when offspring also ingest acrylamide. • Regulation of the gst-4 gene in the detoxification pathway reduces toxicity. [ABSTRACT FROM AUTHOR]

Novel microbial strains capable of efficient degradation of TNT and typical intermediates (2-ADNT and 4-ADNT) in aerobic/anaerobic environment were screened and isolated from ammunition-contaminated sites. The key genomes, transcriptomes, proteins, and metabolic factors for microbial detoxification/tolerance to pollutants in anaerobic and aerobic environments were analyzed for the first time. The bacterial genome, which is rich in metabolism and environmental information-processing functional genes, provides transcriptional and translational-related proteins for detoxifying/tolerating pollutants. At the transcriptional level, bacteria significantly expressed genes related to inositol phosphate metabolism for regulating membrane transport, maintaining the cytoskeleton, and signal transduction. At the protein level, genes involved in antioxidation, fat metabolism, sugar synthesis/degradation, and pyruvate metabolism were significantly expressed. At the metabolic level, riboflavin metabolism, which regulates membrane integrity, protects against oxidative stress, and maintains the sugar–protein–fat balance, showed significant responses. Bacteria simultaneously regulate amino acid metabolism, carbohydrate metabolism, and N/P/S cycles to maintain homeostatic cellular energy supplies. The key pathway for pollutant degradation in bacteria is nitrotoluene degradation. The molecular mechanism of bacterial tolerance to pollutants involves the regulation of oxidative phosphorylation and basic cycle pathways to maintain gene transcription, protein translation, and metabolic cycles. [Display omitted] • Bacillus cereus degrades TNT, 2-ADNT and 4-ADNT efficiently in anaerobic/aerobic environment. • The key regulatory elements on the surface of bacterial membrane are N and Na. • Metabolism and Environmental Information Processing genes affect the detoxification level. • Amino acid metabolism, Carbohydrate metabolism and N/P/S cycles are involved in maintaining homeostasis. • The key pathway for pollutant degradation by the bacteria was nitrotoluene degradation. [ABSTRACT FROM AUTHOR]

Heterothermic insectivorous bats are supposed to experience differential adverse effects of insecticidal pollutants depending on their seasonal and/or daily variation of metabolic and detoxification rates. Here, we investigated effects of imidacloprid, cypermethrin and fipronil on Nyctalus noctula bat-derived hepatocytes through cytotoxicity, cell inhibition and death at different concentrations (0.01, 0.1, 1, 10, 100, 1000 μg/ml), exposure times (10, 24, 48 hrs), incubation temperatures simulating hibernation (8 °C), daily torpor (20 °C), normothermy (37 °C) and active flight (40 °C), and cytochrome P450 addition. Toxic effects were significantly influenced by temperature (p < 0.05), with strong cytotoxicity after 10 hour exposure to fipronil or cypermethrin at 37 and 40 °C, cell replication inhibition (all insecticides at 8 °C) and cellular stimulation, with slight culture proliferation after 48 hours (all insecticides at 40 °C). Replacing protected chiropterans with cell cultures is a way to assess and extrapolate risks of insecticides for bats. • Insecticides are hepatocytotoxic for bats at temperatures of normothermy and flight. • Insecticides inhibit bat hepatocyte replication at hibernation temperature. • Insecticides stimulate compensatory hepatocyte proliferation at higher temperatures. • Cytochrome P450 increases toxic impact of imidacloprid and fipronil in bats. • Cytochrome P450 reduces toxic impact of cypermethrin in bat hepatocytes. [ABSTRACT FROM AUTHOR]

The primary objective was to evaluate the toxicity of triflumezopyrim (TFP) on P. fuscipes larvae and adults at lethal and sublethal levels through topical application. Sublethal effects were assessed by examining developmental period, fecundity, life-table parameters, and fitness parameters. Enzymatic and transcriptional analyses were conducted to determine the impact of TFP on P. fuscipes physiology and gene expression. The LC 50 , LC 30 , and LC 10 of TFP against P. fuscipes larvae and adults were lower than the field-recommended dose (48.75 mg a.i. L−1), indicating direct toxicity and sublethal effects during immature stages. Exposure to LC 30 of TFP extended developmental periods for 2nd-instar larvae and pupae, reduced oviposition, larval predation efficiency, and body weight in both sexes. Sublethal concentrations affected antioxidant, detoxification, and energy reservoir enzymes significantly. Transcriptional analysis revealed impacts on insecticide detoxification, resistance, and stress-related genes. KEGG analysis showed glycerolipid metabolism is the most regulated pathway, and UGT2B10 regulated several detoxification-related pathways under TFP stress. These findings prompt reconsideration of the role of TFP in paddy field IPM due to its adverse effects on P. fuscipes , emphasizing the importance of assessing its ecological impacts before widespread application in agricultural practices. [Display omitted] • Triflumezopyrim (TFP) is toxic to Paederus fuscipes at immature stage on sublethal level. • TFP impacts P. fuscipes fitness at sublethal level. • TFP cause imbalance in antioxidants and Detox enzymes in P. fuscipes. • The energy reserves of P. fuscipes drains during TFP detoxification. • Glycerolipid metabolism pathway and UGT2B10 gene save P. fuscipes from TFP direct toxicity. [ABSTRACT FROM AUTHOR]

Metisa plana is a widespread insect pest infesting oil palm plantations in Malaysia. Farnesyl acetate (FA), a juvenile hormone analogue, has been reported to exert in vitro and in vivo insecticidal activity against other insect pests. However, the insecticidal mechanism of FA on M. plana remains unclear. Therefore, this study aims to elucidate responsive genes in M. plana in response to FA treatment. The RNA-sequencing reads of FA-treated M. plana were de novo -assembled with existing raw reads from non-treated third instar larvae, and 55,807 transcripts were functionally annotated to multiple protein databases. Several insecticide detoxification-related genes were differentially regulated among the 321 differentially expressed transcripts. Cytochrome P450 monooxygenase, carboxylesterase, and ATP-binding cassette protein were upregulated, while peptidoglycan recognition protein was downregulated. Innate immune response genes, such as glutathione S-transferases, acetylcholinesterase, and heat shock protein, were also identified in the transcriptome. The findings signify that changes occurred in the insect's receptor and signaling, metabolic detoxification of insecticides, and immune responses upon FA treatment on M. plana. This valuable information on FA toxicity may be used to formulate more effective biorational insecticides for better M. plana pest management strategies in oil palm plantations. [Display omitted] • Responsive genes after seven days of farnesyl acetate treatment in M. plana were elucidated, including cytochrome P450 monooxygenase, carboxylesterase, ATP-binding cassette protein and peptidoglycan recognition protein. • Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) was identified as hub protein using PPI analysis. • Changes in the regulation of the genes in insect's receptor and signaling, insecticide metabolic detoxification and immune responses were observed. [ABSTRACT FROM AUTHOR]

Pichia kudriavzevii could resist high concentrations of sodium selenite and efficiently biotransform over 80% of the absorbed selenium. However, the specific molecular mechanisms underlying this biotransformation remain unclear. This study aimed to investigate the mechanism of selenium biotransformation focusing on selenium transport, detoxification, reduction, and the formation of organic selenium compounds through a comprehensive approach combining transcriptomic, proteomic, and non-targeted metabolomic analyze. Results showed that the JEN1 gene was responsible for selenium transport, while the upregulation of cysJ , CYSK , TRXB1 and sat genes as well as the involvement of glutathione, are crucial for the accumulation of organic selenium. Furthermore, GSTY2 , TRXB1 and GPX3 were pivotal genes in Se(IV) reduction and their corresponding proteins were key proteins. Additionally, the enhanced expression of genes related to antioxidant enzymes (GSTY2 , TRXB1 , and GPX3), ABC transports, heat shock proteins and antioxidant enzymes proteins (GSTY2, TRXB1, and GPX3) collectively contributed to selenium tolerance, detoxification and protection against oxidative damage. GO and KEGG analysis highlighted alterations in amino acid metabolism, carbohydrate metabolism, and energy metabolism in the selenium biotransformation process. These findings provide novel insight into the mechanisms of selenium biotransformation in P. kudriavzevii and its application in the fields of the food industry. [Display omitted] • The cysJ, CYSK TRXB1 and sat genes played important roles in high content of organic Se. • The high expression of JEN1 involved in the uptake sodium selenite. • TRXB1 and GPX3 were pivotal genes and their corresponding proteins were key proteins in Se (Ⅳ) reduction. • The ABC transports, antioxidant enzymes and HSPs contributed to the Se tolerance. [ABSTRACT FROM AUTHOR]

Quercetin is considered a natural supplement product for its antioxidant, anti-inflammatory and contributes to cardiovascular protection. "Fescue toxicosis" is caused by the consumption of endophyte-positive tall fescue, negatively affecting the livestock cardiovascular system. The present study was to elaborate the protective mechanisms of quercetin against fescue toxicosis-induced cardiovascular toxicity. Twenty-four Dorper sheep were divided into four groups (n = 6). The groups included the E−,Q-group as the control group, fed endophyte-free fescue seed. The E+,Q-group was fed endophyte-positive fescue seed, while the E+,Q+ group received endophyte-positive fescue seed along with 4 mg of quercetin per kilogram of feed. The E−,Q+ group was fed endophyte-free fescue seed along with 4 mg of quercetin per kilogram of feed. The dietary regimens were maintained for a duration of 6 weeks. This study illustrated that quercetin effectively attenuated histological damage to the cardiovascular system and mitigated the increase in white cell counts. However, quercetin did not exert a significant impact on lowering serum prolactin levels. The compound demonstrated regulatory effects on Phase I detoxification enzymes, specifically cytochrome P450 (CYP450) family 1, 2, 3 (CYP1, CYP2, CYP3), by modulating the activity of nuclear receptors aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR). Furthermore, quercetin exhibited regulatory influence on nuclear factor erythroid 2-related factor 2 (NRF2), resulting in a substantial upregulation of antioxidant genes, notably NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1), and glutathione s-transferase (GST), among others. Additionally, quercetin significantly enhanced the mRNA expression of ATP binding cassette transporters, specifically ATP binding cassette subfamily C member 1 (ABCC1) and ATP binding cassette subfamily B member 1 (ABCB1). The study revealed that quercetin modulates the expression of detoxification metabolic enzymes by influencing AHR/NRF2/ABCC1, thereby attenuating the cardiovascular toxicity caused by fescue toxicosis. [Display omitted] • Quercetin attenuated fescue toxicosis-cardiovascular morphological lesions and leukocytosis. • Quercetin relieved the homeostasis of CYP450 enzymes disturbance by regulating NRs. • Quercetin alleviated reduction in phase II detoxification enzymes expression. • Quercetin mitigated the inhibition of the expression of ABC transporters. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exposure to morphine and cocaine induces changes in the transcriptome of zebrafish embryos. • Pathways related to lipid metabolism appear to be overrepresented for both treatments. • Other deregulated pathways are detoxification, response to chemicals and calcium signalling. • Morphine and cocaine modify global DNA methylation. Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse. [ABSTRACT FROM AUTHOR]

Frequent use of insecticide causes an environmental hazard, and also leads pest to develop insecticide resistance. Enhancement of metabolic detoxification and reduction of target sensitivity are the primary mechanism of insecticide resistance. Clarifying the regulatory pathway of resistance mechanism states a pivotal theoretical foundation of delaying insecticide resistance development. Here, we show that three endogenous microRNAs, PC-3p-2522_840, PC-3p-446_6601 and PC-5p-3096_674, are required for the small brown planthopper (SBPH) to modulate triflumezopyrim tolerance via activating pathways of three metabolic detoxification phases. Twenty-one down-regulated miRNAs were acquired, and PC-5p-3096_674, PC-3p-446_6601 and PC-3p-2522_840 were the three most significantly down-regulated miRNAs during triflumezopyrim exposure. The mortality of SBPH was significantly increased after over-supplementation of PC-5p-3096_674, PC-3p-446_6601 and PC-3p-2522_840, with triflumezopyrim exposure. Moreover, the interactions between PC-3p-2522_840 and cytochrome P450 CYP6FL1 , PC-3p-446_6601 and glutathione S-transferase GSTD2 , UDP-Glycosyltransferase UGT386F1 , PC-5p-3096_674 and ATP-binding cassette transporters ABCA3 were systematically demonstrated through the dual luciferase reporter assay. Besides, the mortality of SBPH was significantly increased after knockdown of CYP6FL1 , GSTD2 , UGT386F1 and ABCA3 with triflumezopyrim exposure. These findings uncover a strategy whereby the SBPH weakens three endogenous microRNAs to activate pathways of three metabolic detoxification phases via targeting CYP6FL1 , GSTD2 , UGT386F1 and ABCA3 and promotes its tolerance to triflumezopyrim. • The endogenous miRNAs are necessary for triflumezopyrim (TFM) tolerance in SBPH. • Three metabolic phases are activated by endogenous miRNAs in SBPH. • SBPH weakens miRNA to activate metabolic genes and promotes its tolerance to TFM. [ABSTRACT FROM AUTHOR]

As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis. Herein, we prepared AE@RBC/Fe nanocrystals (NCs) with synergistic PDT and ferroptosis therapeutic effects by one-step emulsification to obtain AE NCs cores and further modification of red blood cells (RBC) membranes and ferritin. Benefiting from the involvement of ferritin, the prepared AE@RBC/Fe NCs provide not only sufficient oxygen for oxygen-dependent PDT, but also Fe3+ for iron-dependent ferroptosis in tumor cells. Furthermore, the biomimetic surface functionalization facilitated the prolonged circulation and cancer targeting of AE@RBC/Fe NCs in vivo. The in vitro and in vivo results demonstrate that AE@RBC/Fe NCs exhibit significantly enhanced therapeutic effects for the combined two antitumor mechanisms and provide a promising prospect for achieving PDT/ferroptosis synergistic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The metabolism of xenobiotic chemicals from the environment can produce reactive oxygen species leading to oxidative stress that is detrimental to the cell. To study the environmental factors that influence oxidative stress, we employed C. elegans engineered with a GFP tagged to the glutathione s-transferase 4 gene encoding a phase II enzyme as a biomarker for oxidative stress to screen against the U.S. EPA Toxcast library containing 4665 unique chemicals. We identified 49 chemicals that induced oxidative stress, as indicated by an increase in gst-4p ::GFP signal. Quantitative PCR was used to measure the changes in mRNA expression corresponding to phase II detoxification enzymes to confirm the induction of oxidative stress for the top 10 chemicals. Among these chemicals include pesticides such as tepraloxydim, dichlone, pentachloronitrobenzene, and common industrial reagents such as ethyl acrylate and dinitrochlorobenzene. Overall, this study presents a comprehensive screening and identification of environmentally relevant chemicals that pose potential cellular toxicity as inducers of oxidative stress. [Display omitted] • C. elegans expressing gst-4p :GFP is an in vivo sensor for oxidative stress. • 4665 chemicals from the U.S. EPA ToxCast Library were screened for oxidative stress. • Pesticides and industrial compounds were abundant among 59 oxidative stress inducing chemicals. [ABSTRACT FROM AUTHOR]

Consento (CON) poses a significant environmental hazard as a systemic fungicide, adversely affecting the health of non-target organisms. Nitric oxide (NO), a signaling molecule, is known to play a crucial role in plant physiology and abiotic stress tolerance. However, whether NO plays any role to enhance fungicide CON tolerance in wheat seedlings is yet unclear. Therefore, we conducted a hydroponic experiment i) to investigate the morpho-physio-biochemical changes of wheat seedlings to fungicide CON stress, and ii) to examine the effects of NO and fungicide CON treatments on oxidative damage, antioxidant system, secondary metabolism and detoxification of systemic fungicide in wheat seedlings. The results showed that CON fungicide at the highest (4X) concentration significantly decreased wheat seedlings fresh weight (46.89%), shoot length (40.26%), root length (56.11%) and total chlorophyll contents (67.44%) in a dose response relationship. Moreover, CON significantly increased hydrogen peroxide, malondialdehyde, catalase, ascorbate peroxidase, glutathione-S-transferase, and peroxidase activities while decreased reduced glutathione (GSH) content. This ultimately impaired the redox homeostasis of cells, leading to oxidative damage in cell membrane. Under fungicide treatment, the addition of NO reduced the fungicide phytotoxicity, with an increase of over 60% in seedling growth. The NO application mitigated CON phytotoxicity as reflected by significantly increased chlorophyll pigments (69.88%) and decreased oxidative damage in wheat leaves. Indeed, the NO alleviatory effect was able to increase the tolerance of seedlings to fungicide, which resulted increments in antioxidant and detoxification enzymes activity, with the enhanced GSH level (78.54%). Interestingly, NO alleviated CON phytotoxicity through the phenylpropanoid pathway by enhancing the activity of secondary metabolism enzymes such as phenylalanine ammonia-lyase (47.28%), polyphenol oxidase (9%), and associated metabolites such as phenolic acids (77.62%), flavonoids (34.33%) in wheat leaves. Our study has provided evidence that NO plays a key role in the metabolism and detoxification of systemic fungicide in wheat through enhanced activity of antioxidants, detoxifications and secondary metabolic enzymes. [Display omitted] • Consento fungicide causes oxidative damage and phytotoxicity in wheat seedlings. • NO alleviates Consento toxicity by scavenging ROS and improved carotenoid content. • NO regulates enzymatic and non-enzymatic antioxidants in wheat exposed to Consento. • NO stimulates PPO and PAL enzymatic pathway to detoxify Consento toxicity in wheat. [ABSTRACT FROM AUTHOR]

Tagetes patula L. (T. patula) is a Cd hyperaccumulator plant with high ornamental value and strong resistance. Understanding the molecular mechanisms of Cd tolerance in hyper-accumulating plants is important for improving phytoremediation efficiency. This investigation studied to how Cd affected T. patula 's physiological characteristics and molecular alterations. With the increase of Cd concentration, chlorophyll content, and root biomass decreased; the activities of antioxidant enzymes such as GST, SOD and POD increased. Initially, Cd accumulated mainly in the root and then transferred upward to the leaves. The molecular mechanisms of T. patula after 150 mg/kg and 250 mg/kg treatments were analyzed by transcriptome. In total, 5429 and 6546 differentially expressed unigenes were identified. Phenylpropanoid biosynthesis and phenylalanine metabolism were identified as key pathways in reaction to Cd stress. In addition, many differential genes involved in the response to Cd stress were identified, including heavy metal transporter protein genes, genes and transcription factors related to Cd detoxification. These results indicate that the response of T. patula to Cd was multifaceted, laying the foundation for studies to improve its tolerance to toxic metals. [Display omitted] • Antioxidant enzymes and GSH were increased under Cd stress. • T. patula has a strong capacity for Cd accumulation and translocation. • Many genes were identified as Cd-induced differentially expressed genes. • Phenylpropanoid metabolism play important roles in Cd tolerance in T. patula. [ABSTRACT FROM AUTHOR]

[Display omitted] • The core–shell composite was prepared for degradation of chemical warfare agents. • The core–shell catalyst displayed high recovery and good bio-compatibility. • ILs helped catalyst to boost enrichment capacity and catalytic rates. • DFT calculation helped to reveal the catalytic mechanism and degradation pathways. Detoxicating materials of chemical warfare agents (CWAs) and their simulants play a critical role in reducing pollution contamination and environmental renovation. In this work, we present a simple strategy to prepare a core–shell structure Fe 3 O 4 /UiO-66-NH 2 /ILs@mSiO 2 using hydrogen bonding association and electrostatic forces. We performed disinfection studies on dimethyl 4-nitrophenyl phosphate (DMNP) and 2-chloroethyl ethyl sulfide (2-CEES). The synergistic effects of catalytic activations for CWAs, which reduce the electron transport distance and lower the reaction energy barrier, lead to an increase in hydrolysis and Fenton-like reactions efficiency. Eliminationing tests of DMNP and 2-CEES showed that the half-lives of the degradation reactions were 128.36 and 1.12 min, respectively, and the degradation efficiency did not decrease significantly after 4 cycles. This new type of structure could be magnetically separated within 60 s to facilitate material recovery and reuse. Moreover, the presence of a mesoporous silica shell made the catalyst particles to become biocompatible and environmentally friendly. The degradation pathways of the intermediates were revealed based on nuclear magnetic resonance spectroscopy (NMR), gaschromatography-mass spectrometry (GC–MS) and density functional theory (DFT) calculations. The effective combination of catalysts provided a facile strategy for developing multi-effect synergistic catalysts for the elimination of CWAs and other pollutants. [ABSTRACT FROM AUTHOR]

Antibiotic production wastewater exhibits high concentration of antibiotics and toxic intermediates, which would pose a serious threat to the ecological environment. The biodegradation methods are prevailing for this wastewater. However, it imposes a considerable toxic burden on biological treatment units in wastewater treatment plants (WWTPs), ultimately resulting in subpar treatment efficacy. For improving the biodegradability of antibiotic production wastewater, hybrid process of resin adsorption and Fenton oxidation was proposed. The adsorption experiments showed that NDA-150 exhibited removal rates of up to 99.1% and 94.8% for two key pollutants 8-hydroxyquinoline (8HQ) and o -aminophenol (OAP), respectively. The constant removal rates demonstrated stable performance and capacity of NDA-150 for practical industrial operation. The remaining high COD due to other organic contaminants in the effluent required the involvement of Fenton oxidation for the further processing. The results of single factor experiments and orthogonal tests showed that the COD removal rate of 56.5% could be realized under the optimal operating conditions. This work proposed a novel process which could alleviate obstacles between the antibiotic manufacture factories and biological treatment units, shed light on the mechanisms and feasibility of it, and provide a promising avenue for the toxicant organic industrial sewage. [Display omitted] • Novel hybrid process was proposed and effectiveness was remarkable. • Dynamic adsorption and orthogonal design tests were performed to guide the real application. • Multiple biotoxicity assessment was conducted to assess performance. • Actual high-concentration antibiotic production wastewater was adopted. [ABSTRACT FROM AUTHOR]

The misuse of pharmaceuticals has significantly increased in recent decades, becoming a major public health concern. The risks associated with medication misuse are particularly high in cases of overdose, especially when the active substances are chiral, as enantioselectivity plays an important role in toxicity. Promethazine (PMZ) is a chiral antihistamine marketed as a racemate and it is misused in "Purple Drank", a recreational drug beverage, that combines codeine and/or PMZ, with soda or alcohol leading to serious health consequences and fatalities in consumers around the world, particularly among teenagers. Information regarding the enantioselectivity in the toxicity of (R,S)-PMZ and its main metabolites, namely promethazine sulfoxide (PMZSO) and desmonomethyl promethazine (DMPMZ), is unknown. This work reported, for the first time, the enantioseparation, in milligram scale, of (R,S)-PMZ, (R,S)-DMPMZ, (R,S)- PMZSO and the determination of their absolute configurations by electronic circular dichroism (ECD). The enantioseparation of all the six enantiomers was accomplished in a homemade semi-preparative column with amylose tris- 3,5-dimethylphenylcarbamate (AD) coated with aminopropyl Nucleosil silica. The enantiomeric purity was evaluated using the analytical Lux® 3 µm i-Amylose-3 column, yielding enantiomeric purity values ranging between 94.4% and 99.7%. The elution order of all the enantiomers was accomplished combining the ECD results with an optical rotation detector. The elution order of the enantiomers was influenced only by the chiral selector, rather than the mobile phase. The cytotoxicity of the racemates and the isolated enantiomers towards differentiated SH-SY5Y cells was evaluated. (R,S)-DMPMZ exhibited a significantly higher cytotoxicity than (R,S)-PMZ, suggesting the metabolic bioactivation of (R,S)-PMZ. Conversely, no significant cytotoxicity was found for (R,S)-PMZSO, underscoring a metabolic detoxification pathway. Remarkably, enantioselectivity was observed for the cytotoxicity of PMZ; (R)-PMZ was significantly more cytotoxic than (S)-PMZ. The results underscore the importance to isolate the enantiomers in their enantiomerically form and their correct identification for toxicity enantioselectivity studies, which are vital to understand the drug's behaviour and safety, especially in case of overdoses. • Semi-preparative enantioseparation of promethazine and its metabolites: PMZSO and DMPMZ. • Absolute configuration and elution order confirmation of the enantiomers of promethazine and its main metabolites. • (R)-Promethazine displayed a significantly higher cytotoxicity than the (S) enantiomer towards dopaminergic neuronal cells. • N -desmonomethyl promethazine exhibited higher cytotoxicity than promethazine in differentiated SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Interspecific interactions are central to ecological research. Plants produce toxic plant secondary metabolites (PSMs) as a defense mechanism against herbivore overgrazing, prompting their gradual adaptation to toxic substances for tolerance or detoxification. P450 enzymes in herbivore livers bind to PSMs, whereas UDP-glucuronosyltransferase and glutathione S-transferase increase the hydrophobicity of the bound PSMs for detoxification. Intestinal microorganisms such as Bacteroidetes metabolize cellulase and other macromolecules to break down toxic components. However, detoxification is an overall response of the animal body, necessitating coordination among various organs to detoxify ingested PSMs. PSMs undergo detoxification metabolism through the liver and gut microbiota, evidenced by increased signaling processes of bile acids, inflammatory signaling molecules, and aromatic hydrocarbon receptors. In this context, we offer a succinct overview of how metabolites from the liver and gut microbiota of herbivores contribute to enhancing metabolic PSMs. We focused mainly on elucidating the molecular communication between the liver and gut microbiota involving endocrine, immune, and metabolic processes in detoxification. We have also discussed the potential for future alterations in the gut of herbivores to enhance the metabolic effects of the liver and boost the detoxification and metabolic abilities of PSMs. [Display omitted] • Liver detoxifies toxic components through P450 binding and UGT protein transport. • Gut Bacteroides help detoxify toxic components by secreting enzymes and bile acids. • Crucial for detoxification metabolism of toxic plants is the bile acid transport between liver and gut. • Future research should explore synergistic gut-liver pathways for detoxification. [ABSTRACT FROM AUTHOR]

[Display omitted] Xenobiotic metabolic reactions in the hepatocyte endoplasmic reticulum (ER) including UDP-glucuronosyltransferase and carboxylesterase play central roles in the detoxification of medical agents with small- and medium-sized molecules. Although the catalytic sites of these enzymes exist inside of ER, the molecular mechanism for membrane permeation in the ER remains enigmatic. Here, we investigated that organic anion transporter 2 (OAT2) regulates the detoxification reactions of xenobiotic agents including anti-cancer capecitabine and antiviral zidovudine, via the permeation process across the ER membrane in the liver. Pharmacokinetic studies in patients with colorectal cancer revealed that the half-lives of capecitabine in rs2270860 (1324C > T) variants was 1.4 times higher than that in the C/C variants. Moreover, the hydrolysis of capecitabine to 5′-deoxy-5-fluorocytidine in primary cultured human hepatocytes was reduced by OAT2 inhibitor ketoprofen, whereas capecitabine hydrolysis directly assessed in human liver microsomes were not affected. The immunostaining of OAT2 was merged with ER marker calnexin in human liver periportal zone. These results suggested that OAT2 is involved in distribution of capecitabine into ER. Furthermore, we clarified that OAT2 plays an essential role in drug-drug interactions between zidovudine and valproic acid, leading to the alteration in zidovudine exposure to the body. Our findings contribute to mechanistically understanding medical agent detoxification, shedding light on the ER membrane permeation process as xenobiotic metabolic machinery to improve chemical changes in hydrophilic compounds. [ABSTRACT FROM AUTHOR]

In recent years, the acronym NRF2 has garnered significant attention in scientific discourse. However, this attention has occasionally led to confusion due to the existence of two distinct proteins sharing the same acronym: Nuclear Respiratory Factor 2 (NRF2), also known as GA-binding protein transcription factor subunit alpha (GABPA), and Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2 or NRF2). This confusion has been highlighted in various scientific forums, including PubPeer and anonymous reader comments, where the confusion between the two proteins has been expressed. In this article, we aim to elucidate the disparities between these two proteins. Both are transcription factors that play pivotal roles in cellular homeostasis and response to stress, with some overlapping functional aspects. Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2) is a key regulator of the antioxidant response element (ARE) pathway. It functions by binding to antioxidant response elements in the promoters of target genes, thereby orchestrating the expression of various cytoprotective enzymes and proteins involved in detoxification, redox balance, and cellular defense against oxidative stress. Conversely, Nuclear Respiratory Factor 2 (GABPA) is primarily associated with the regulation of mitochondrial biogenesis, in relation to PGC1α, and maintaining cellular energy metabolism. It is important to recognize and differentiate between these two proteins to avoid misconceptions and misinterpretations in scientific literature and discussions. Our laboratories (Arubala P Reddy and P. Hemachandra Reddy) focued on Nuclear Respiratory Factor 2 (NRF2), but not on Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2). We hope that the facts, figures, and discussions presented in this article will clarify the current controversy regarding the sizes, structural features, and functional aspects of these proteins. • In recent years, the acronym NRF2 has garnered significant attention in scientific discourse. • Confusion due to the existence of two proteins sharing the same acronym: Nuclear Respiratory Factor 2 (NRF2) and Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2). • It has been highlighted in various scientific forums, including PubPeer or anonymous reader, where comments expressing confusion between two proteins have emerged. • Nuclear factor erythroid 2-related factor 2, is a key regulator of the antioxidant response element (ARE) pathway. • NRF2, also referred to as GA-binding protein transcription factor subunit alpha (GABPA), is primarily associated with the regulation of mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Environmental pollution and energy scarcity have promoted the development of renewable alternative energy of rice straw-based bioethanol. However, the production of main fermentation inhibitors from the pretreatment of rice straw raw material reduces the bioethanol yield. In order to improve bioethanol production, a waste biomass-based adsorbent (AEPA 250) was used to adsorb three main inhibitors of ferulic acid, vanillin, and furfural from the rice straw hydrolysate in this study. The adsorption percentages were calculated using the high-performance liquid chromatography method. The results showed that the adsorption percentages of three inhibitors were all above 70% in 10 min, demonstrating the efficient detoxification of AEPA 250 on rice straw hydrolysate. The adsorption contributions related to the attribute features of three inhibitors and AEPA 250 were evaluated for the first time. The density functional theory calculations and AEPA 250 characterizations were used to obtain these attribute parameters. Analysis of the correlation heat map between adsorption efficiencies and attribute features of AEPA 250 (or fermentation inhibitors) indicated that AEPA 250 possessed the lower activation energy (E a) and pre-exponential factor (A) when it was prepared, as well as fermentation inhibitors had the higher ionization constant (pKa) and lower electrophilicity index (ω), resulting in the enhancement of bioethanol production. The contribution of pKa was greater than A followed by Ea and ω for adsorption process. Meanwhile, the key metabolic pathways involved in central carbon metabolism were analyzed for AEPA 250 detoxification using proteomics method. The results indicated that the up-regulation of SDH3, ACO1, CIT2 and MLS1 (or down-regulation of SCT1) genes contributed to inhibitors detoxification using AEPA 250 , which effectively provided more nicotinamide adenine dinucleotide (NADH) for the reduction of these inhibitors. This study explores the detoxification mechanisms at the molecular level for boosting bioethanol production in the future, which lays the foundation for the development of efficient adsorbents and resistant engineering strains. [Display omitted] • Three inhibitors of ferulic acid, vanillin and furfural were detoxified by AEPA 250. • The contribution of pKa was greater than A followed by E a for inhibitors adsorption. • Central carbon metabolic pathways provided more NADH to enhance bioethanol yield. • SDH3, ACO1, CIT2, MLS1, and SCT1 genes related to inhibitors detoxification. [ABSTRACT FROM AUTHOR]

Agrochemicals play a vital role in protecting crops and enhancing agricultural production by reducing threats from pests, pathogens and weeds. The toxicological status of honey bees can be influenced by a number of factors, including pesticides. While extensive research has focused on the lethal and sublethal effects of insecticides on individual bees and colonies, it is important to recognise that fungicides and herbicides can also affect bees' health. Unfortunately, in the field, honey bees are exposed to mixtures of compounds rather than single substances. This study aimed to evaluate the effects of a commercial fungicide and a commercial herbicide, both individually and in combination, on honey bees. Mortality assays, biomarkers and learning and memory tests were performed, and the results were integrated to assess the toxicological status of honey bees. Neurotoxicity (acetylcholinesterase and carboxylesterase activities), detoxification and metabolic processes (glutathione S-transferase and alkaline phosphatase activities), immune system function (lysozyme activity and haemocytes count) and genotoxicity biomarkers (Nuclear Abnormalities assay) were assessed. The fungicide Sakura® was found to activate detoxification enzymes and affect alkaline phosphatase activity. The herbicide Elegant 2FD and the combination of both pesticides showed neurotoxic effects and induced detoxification processes. Exposure to the herbicide/fungicide mixture impaired learning and memory in honey bees. This study represents a significant advance in understanding the toxicological effects of commonly used commercial pesticides in agriculture and contributes to the development of effective strategies to mitigate their adverse effects on non-target insects. [Display omitted] • Effects of commercial fungicide and herbicide, single and in combination, were evaluated. • Mortality assay, biomarkers and learning and memory tests were performed on honey bees. • Neurotoxic effects after both mixture treatments could be attributed to the herbicide. • Herbicide and pesticide mixtures compromise honey bees' behaviour. [ABSTRACT FROM AUTHOR]

Pesticides are typically present as combinations within soil ecosystems and have detrimental effects on untamed surroundings. However, the collective impacts and fundamental mechanisms of pesticides on soil living beings are currently inadequately assessed. In our current work, we evaluated the interactive consequences of clothianidin (CLO) and prochloraz (PRO) on earthworms (Eisenia fetida) using several toxicological tests, such as acute adverse effects, biocatalytic activity, and alterations in transcriptional activity. The findings revealed that CLO (with a 14-day LC 50 value of 6.08 mg kg−1) exhibited greater toxicity compared to PRO (with a 14-day LC 50 value of 79.41 mg kg−1). Moreover, the combinations of CLO and PRO had synergistic acute effects on E. fetida. Additionally, the activities of POD, CAT, and GST were significantly varied in most instances of single and mixed treatments when compared to the control. Surprisingly, the transcriptional levels of four genes (gst , sod , crt , and ann), related to oxidative load, metabolic detoxification systems, endoplasmic reticulum, and oxytocin neuropeptide, respectively, were also altered in response to single and mixture exposures, as compared to the control. Alterations in enzyme activity and gene transcriptional level could serve as early indicators for detecting co-exposure to pesticides. The findings of this research offered valuable holistic understanding regarding the toxicity of pesticide combinations on earthworms. Further research should be conducted to investigate the persistent effects of pesticide mixtures on terrestrial invertebrates in order to draw definitive conclusions about the associated risks. [Display omitted] • The acute toxicity of clothianidin was higher than prochloraz to the earthworms. • The combinations of clothianidin and prochloraz induced synergistic acute effects. • CarE possessed important role in the synergism of clothianidin and prochloraz. • Activities of CAT and GST were significantly increased after most of the exposures. • Expression levels of 4 genes in mixtures produced greater changes than individuals. [ABSTRACT FROM AUTHOR]

Unsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C-2028. GSH-supplemented incubations of C-2028 with rat, but not with human, liver cytosol led to the formation of a single GSH-related metabolite. Interestingly, it was also revealed with rat liver microsomes. Its formation was NADPH-independent and was not inhibited by co-incubation with the cytochrome P450 (CYP450) inhibitor 1-aminobenzotriazole. Therefore, the direct conjugation pathway occurred without the prior CYP450-catalyzed bioactivation of the substrate. In turn, incubations of C-2028 and GSH with human recombinant glutathione S-transferase (GST) P1-1 or with heat-/ethacrynic acid-inactivated liver cytosolic enzymes resulted in the presence or lack of GSH conjugated form, respectively. These findings proved the necessary participation of GST in the initial activation of the GSH thiol group to enable a nucleophilic attack on the substrate molecule. Another C-2028-GSH S-conjugate was also formed during non-enzymatic reaction. Both GSH S-conjugates were characterized by combined liquid chromatography/tandem mass spectrometry. Mechanisms for their formation were proposed. The ability of C-2028 to GST-mediated and/or direct GSH conjugation is suspected to be clinically important. This may affect the patient's drug clearance due to GST activity, loss of GSH, or the interactions with GSH-conjugated drugs. Moreover, GST-mediated depletion of cellular GSH may increase tumor cell exposure to reactive products of UA metabolic transformations. [Display omitted] • We investigated the GSH-mediated metabolic pathway of antitumor bisacridine C-2028. • Non-enzymatic and GST-catalyzed GSH conjugation of C-2028 was observed. • The action of human recombinant GSTP1-1 in C-2028 metabolism was proved. • GSH conjugation occurred without the prior CYP450-mediated activation of C-2028. • GSH conjugation of C-2028 molecule took place on the system containing nitro group. [ABSTRACT FROM AUTHOR]

[Display omitted] • Casein-bound LL might be metabolized and transformed into 3-DG with the participation of FN3K in vivo. • Casein-bound LL intake induced dicarbonyl stress to promote the formation of AGEs in tissues/organs and systemic inflammation. • The formation levels of AGEs in organs/tissues at different casein-bound LL intake stages varied with the changes in the expression of FN3K and α-DCs metabolic enzymes. • The negative effects caused by casein-bound LL intake could not be fully recovered by switching to a standard diet for equal periods. Lactulosyllysine (LL) widely exists in thermally processed dairy products, while the metabolism and transformation of LL remain poorly understood. We aimed to elucidate the metabolic pathways of LL and its impact on body health by subjecting C57BL/6 mice to a short-term ll -fortified casein diet. Our findings indicated that casein-bound LL might be metabolized and transformed into 3-deoxyglucosone through fructosamine-3-kinase (FN3K) in vivo , which promoted α-dicarbonyl stress, ultimately leading to the formation of advanced glycation end products (AGEs) in various tissues/organs, accompanied by systemic inflammation. The levels of AGEs formation in tissues/organs at various stages of casein-bound LL intake exhibited dynamic changes, correlating with alterations in the expression of FN3K and α-dicarbonyl compounds metabolic detoxification enzymes. The negative effects induced by casein-bound LL cannot be fully reversed by switching to a standard diet for equal periods. Consumption of dairy products rich in LL raises concerns as a potential risk factor for healthy individuals. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a signaling molecule with diverse roles in various organisms. However, its role in the opportunistic pathogen Aspergillus flavus remains unclear. This study investigates the potential of NO, mediated by metabolites from A. oryzae (AO), as an antifungal strategy against A. flavus. We demonstrated that AO metabolites effectively suppressed A. flavus asexual development, a critical stage in its lifecycle. Transcriptomic analysis revealed that AO metabolites induced NO synthesis genes, leading to increased intracellular NO levels. Reducing intracellular NO content rescued A. flavus spores from germination inhibition caused by AO metabolites. Furthermore, exogenous NO treatment and dysfunction of flavohemoglobin Fhb1, a key NO detoxification enzyme, significantly impaired A. flavus asexual development. RNA-sequencing and metabolomic analyses revealed significant metabolic disruptions within tricarboxylic acid (TCA) cycle upon AO treatment. NO treatment significantly reduced mitochondrial membrane potential (Δψm) and ATP generation. Additionally, aberrant metabolic flux within the TCA cycle was observed upon NO treatment. Further analysis revealed that NO induced S-nitrosylation of five key TCA cycle enzymes. Genetic analysis demonstrated that the S-nitrosylated Aconitase Acon and one subunit of succinate dehydrogenase Sdh2 played crucial roles in A. flavus development by regulating ATP production. This study highlights the potential of NO as a novel antifungal strategy to control A. flavus by compromising its mitochondrial function and energy metabolism. [Display omitted] ● oryzae metabolites inhibit A. flavus development by inducing NO production. ● NO disrupts A. flavus mitochondrial function and TCA metabolism. ● NO induces S-nitrosylation of key TCA enzymes. ● Aconitase and Succinate dehydrogenase are crucial targets for NO-mediated antifungal activity. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) hazard is a serious limitation to plants, soils and environments. Cd-toxicity causes stunted growth, chlorosis, necrosis, and plant yield loss. Thus, ecofriendly strategies with understanding of molecular mechanisms of Cd-tolerance in plants is highly demandable. The Cd-toxicity caused plant growth retardation, leaf chlorosis and cellular damages, where the glutathione (GSH) enhanced plant fitness and Cd-toxicity in Brassica through Cd accumulation and antioxidant defense. A high-throughput proteome approach screened 4947 proteins, wherein 370 were differently abundant, 164 were upregulated and 206 were downregulated. These proteins involved in energy and carbohydrate metabolism, CO 2 assimilation and photosynthesis, signal transduction and protein metabolism, antioxidant defense response, heavy metal detoxification, cytoskeleton and cell wall structure, and plant development in Brassica. Interestingly, several key proteins including glutathione S-transferase F9 (A0A078GBY1), ATP sulfurylase 2 (A0A078GW82), cystine lyase CORI3 (A0A078FC13), ferredoxin-dependent glutamate synthase 1 (A0A078HXC0), glutaredoxin-C5 (A0A078ILU9), glutaredoxin-C2 (A0A078HHH4) actively involved in antioxidant defense and sulfur assimilation-mediated Cd detoxification process confirmed by their interactome analyses. These candidate proteins shared common gene networks associated with plant fitness, Cd-detoxification and tolerance in Brassica. The proteome insights may encourage breeders for enhancing multi-omics assisted Cd-tolerance in Brassica, and GSH-mediated hazard free oil seed crop production for global food security. [Display omitted] • Glutathione enhances cadmium tolerance by inhibiting cadmium accumulation in Brassica napus. • Glutathione improves plant fitness by restoring photosynthetic pigments and enhancing key antioxidant enzymes. • Glutathione reduces the enrichment of superoxide (O 2 .-) and hydrogen peroxide (H 2 O 2). • Glutathione triggers several key proteome mechanisms, including antioxidant defense, sulfur assimilation, and cadmium detoxification. • Key protein networks disclose promising advancements in multiomics-assisted breeding of Brassica napus. [ABSTRACT FROM AUTHOR]

Glycation is a posttranslational modification of proteins that contributes to the vast array of biological information that can be conveyed via a singular proteome. Understanding the role of advanced glycation end-products (AGEs) in human health and pathophysiology can be difficult, as the physiological effects of AGEs have been associated with multiple biological processes and disease state development, including acute myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis, as well as tumor cell migration. The critical role of the glyoxalase system in the detoxification of methylglyoxal and other AGEs has been well established. Recently, evidence has emerged that DJ-1 displays antiglycative activity and may contribute to another mechanism of protection against protein glycation outside of the glyoxalase system. Identification of potential substrates of DJ-1 and determination of the pathways in which DJ-1 operates, is needed to fully understand the role of this protein in modulating biological homeostasis and the development of disease. [ABSTRACT FROM AUTHOR]

The methylimidazolium ionic liquid M8OI (1-octyl-3-methylimidazolium chloride, also known as [C8mim]Cl) has been detected in the environment and may represent a hazard trigger for the autoimmune liver disease primary biliary cholangitis, based in part on studies using a rat liver progenitor cell. The effect of M8OI on an equivalent human liver progenitor (undifferentiated HepaRG cells; u-HepaRG) was therefore examined. u-HepaRG cells were less sensitive (>20-fold) to the toxic effects of M8OI. The relative insensitivity of u-HepaRG cells to M8OI was in part, associated with a detoxification by monooxygenation via CYP3A7 followed by further oxidation to a carboxylic acid. Expression of CYP3A7 - in contrast to the related adult hepatic CYP3A4 and CYP3A5 forms - was confirmed in u-HepaRG cells. However, blocking M8OI metabolism with ketoconazole only partly sensitized u-HepaRG cells. Despite similar proliferation rates, u-HepaRG cells consumed around 75% less oxygen than B-13 cells, reflective of reduced dependence on mitochondrial activity (Crabtree effect). Replacing glucose with galactose, resulted in an increase in u-HepaRG cell sensitivity to M8OI, near similar to that seen in B-13 cells. u-HepaRG cells therefore show reduced sensitivity to the toxic effects of M8OI through a combination of metabolic detoxification and their reduced reliance on mitochondrial function. [ABSTRACT FROM AUTHOR]

Imidacloprid enters the water environment through rainfall and causes harm to aquatic crustaceans. However, the potential chronic toxicity mechanism of imidacloprid in crayfish has not been comprehensively studied. In this study, red claw crayfish (Cherax quadricarinatus) were exposed to 11.76, 35.27, or 88.17 μg/L imidacloprid for 30 days, and changes in the physiology and biochemistry, gut microbiota, and transcriptome of C. quadricarinatus and the interaction between imidacloprid, gut microbiota, and genes were studied. Imidacloprid induced oxidative stress and decreased growth performance in crayfish. Imidacloprid exposure caused hepatopancreas damage and decreased serum immune enzyme activity. Hepatopancreatic and plasma acetylcholine decreased significantly in the 88.17 μg/L group. Imidacloprid reduced the diversity of the intestinal flora, increased the abundance of harmful flora, and disrupted the microbiota function. Transcriptomic analysis showed that the number of up-and-down-regulated differentially expressed genes (DEGs) increased significantly with increasing concentrations of imidacloprid. DEG enrichment analyses indicated that imidacloprid inhibits neurotransmitter transduction and immune responses and disrupts energy metabolic processes. Crayfish could alleviate imidacloprid stress by regulating antioxidant and detoxification-related genes. A high correlation was revealed between GST , HSPA1s , and HSP90 and the composition of gut microorganisms in crayfish under imidacloprid stress. This study highlights the negative effects and provides detailed sequencing data from transcriptome and gut microbiota to enhance our understanding of the molecular toxicity of imidacloprid in crustaceans. [Display omitted] • Imidacloprid strongly inhibited the growth performance of Cherax quadricarinatus. • Imidacloprid suppressed immunity and caused hepatopancreatic damage in C. quadricarinatus. • Imidacloprid reduces the diversity and destroys the balance in the intestinal flora of crayfish. • Imidacloprid may alter gene expression by affecting intestinal flora. [ABSTRACT FROM AUTHOR]

The superior electrocatalytic hydrodechlorination (EHDC) performance on Pd/U-TiO 2 catalyst is attributed to the electron-rich Pd regulated by urchin-like yolk/shell TiO 2 support, enhanced adsorption and activation of 2,4-dichlorophenol, faster mass diffusion behavior and high current efficiency toward EHDC. [Display omitted] • Pd supported on urchin-like yolk/mesoporous shell TiO 2 (Pd/U-TiO 2) is prepared. • Pd/U-TiO 2 affords high efficiency and durability in EHDC of 2,4-DCP. • Pd/U-TiO 2 affords a higher H* utilization efficiency of 48.6 % than single Pd. • U-TiO 2 support boosts the mass diffusion of 2,4-DCP around Pd nanoparticles. • The pollutant adsorption and activation are enhanced on U-TiO 2 -supported Pd. Improving the utilization of hydrogen radicals (H*) is of great significance for effective Pd-mediated electrocatalytic hydrodechlorination (EHDC) in detoxifying chlorinated organic pollutants (COPs). However, the limited H* utilization by single Pd arises from its inadequate performance in adsorbing/activating COPs and inferior mass transfer of low-concentration COPs. In this study, an urchin-like yolk/shell TiO 2 spheres with mesoporous structure are developed for supporting Pd nanoparticles (Pd/U-TiO 2), which exhibits superior EHDC activity and selectivity for 2,4-DCP reduction. Notably, the prepared Pd/U-TiO 2 catalyst achieves a mass activity of 4.2 min−1 g Pd -1 and a specific activity of 1.94 min−1 mol Pd -1 when detoxifying 50 mg/L of 2,4-DCP at −0.85 V, surpassing the most reported catalysts. Furthermore, the Pd/U-TiO 2 catalyst consistently demonstrates higher H* utilization efficiency compared to single Pd, regardless of the 2,4-DCP concentration or reaction mode (batch or continuous-flow). This enhanced H* utilization efficiency is attributed to two key factors: the urchin-like and yolk/shell structure of U-TiO 2 enhances the mass diffusion of 2,4-DCP, and the strong interactions between Pd and U-TiO 2 generate electron-rich Pd species that enhance the adsorption and activation of COPs. Overall, this work highlights the synergistic effects of strong metal-support interactions and mass diffusion in enhancing atomic H* utilization. This study lays a significant experimental and theoretical foundation for designing efficient electrocatalysts for the detoxification of chlorinated organic pollutants and various other halogenated organic pollutants. [ABSTRACT FROM AUTHOR]

Shortawn foxtail (Alopecurus aequalis Sobol.) is a noxious weed in China. The resistance of A. aequalis developed rapidly due to the long-term application of acetolactate synthase (ALS)-inhibiting herbicides. Here, a suspected mesosulfuron-methyl - resistant A. aequalis population, Aa-R, was collected from a wheat field in China. A dose‒response test showed that the Aa-R population has evolved a high level of resistance to mesosulfuron-methyl, and its growth was suppressed by imazamox, pyroxsulam and bispyribac-sodium. ALS gene sequence analysis revealed that a known resistance-related mutation (Pro-197-Thr) was present in the Aa-R population. Moreover, ALS gene overexpression was detected in the Aa-R population. The mesosulfuron-methyl resistance could be reversed by cytochrome P450 monooxygenase (CYP450) and glutathione S-transferase (GST) inhibitors. In addition, enhanced metabolism of mesosulfuron-methyl was detected in the Aa-R population compared with the susceptible population. NADPH-cytochrome P450 reductase and GST activities were strongly inducible in the Aa-R population. One CYP450 gene, CYP74A2 , and one GST gene, GST4 , were constitutively upregulated in the Aa-R population. Molecular docking results showed the binding affinity of CYP74A2 and GST4 for the tested ALS-inhibiting herbicides, respectively. This study confirmed that target-site resistance and non-target-site resistance involving CYP450 and GST were the main mechanisms involved in resistance in the mesosulfuron-methyl-resistant A. aequalis population. [Display omitted] • TSR and NTSR coexist in the mesosulfuron-methyl-resistant A. aequalis population. • CYP74A2 and GST4 may be involved in mesosulfuron-methyl metabolism in A. aequalis. • Molecular docking demonstrated herbicide-gene interaction in A. aequalis. [ABSTRACT FROM AUTHOR]

The pesticide application method is one of the important factors affecting its effectiveness and residues, and the risk of pesticides to non-target organisms. To elucidate the effect of application methods on the efficacy and residue of cyenopyrafen, and the toxic effects on pollinators honeybees in strawberry cultivation, the efficacy and residual behavior of cyenopyrafen were investigated using foliar spray and backward leaf spray in field trials. The results showed that the initial deposition of cyenopyrafen using backward leaf spray on target leaves reached 5.06–9.81 mg/kg at the dose of 67.5–101.25 g a.i./ha, which was higher than that using foliar spray (2.62–3.71 mg/kg). The half-lives of cyenopyrafen in leaves for foliar and backward leaf spray was 2.3–3.3 and 5.3–5.9 d, respectively. The residues (10 d) of cyenopyrafen in leaves after backward leaf spray was 1.41–3.02 mg/kg, which was higher than that after foliar spraying (0.25–0.37 mg/kg). It is the main reason for the better efficacy after backward leaf spray. However, the residues (10 d) in strawberry after backward leaf spray and foliar spray was 0.04–0.10 and < 0.01 mg/kg, which were well below the established maximum residue levels of cyenopyrafen in Japan and South Korea for food safety. To further investigate the effects of cyenopyrafen residues after backward leaf spray application on pollinator honeybees, sublethal effects of cyenopyrafen on honeybees were studied. The results indicated a significant inhibition in the detoxification metabolic enzymes of honeybees under continuous exposure of cyenopyrafen (0.54 and 5.4 mg/L) over 8 d. The cyenopyrafen exposure also alters the composition of honeybee gut microbiota, such as increasing the relative abundance of Rhizobiales and decreasing the relative abundance of Acetobacterales. The comprehensive data on cyenopyrafen provide basic theoretical for environmental and ecological risk assessment, while backward leaf spray proved to be effective and safe for strawberry cultivation. [Display omitted] • The efficacy of cyenopyrafen by backward leaf spray was notably greater than that of foliar spray. • Cyenopyrafen by backward leaf spray had higher deposition and longer half-life than foliar spray. • Cyenopyrafen alters the relative abundance of Rhizobiales and Acetobacterales in honeybee gut. • Host-microbiota interactions resist cyenopyrafen through both immune and metabolic pathways. [ABSTRACT FROM AUTHOR]

Organic and nanoparticle pollutants are the main environmental problems affecting marine species, which have received great attention. However, the combined effect of pollutants on marine life in the presence of predators needs to be clarified. In this study, the effects of pentachlorophenol (PCP) and titanium dioxide nanoparticles (nano-TiO 2) on the energy metabolism of mussels (Mytilus coruscus) in the presence of predators were assessed through cellular energy allocation (CEA) approach. Mussels were exposed to PCP (0, 1, and 10 μg/L), nano-TiO 2 (1 mg/L, 25 and 100 nm), and predators (Portunus trituberculatus presence/absence) for 14 days. Exposure to high concentrations of PCP (10 μg/L) with small particle size nano-TiO 2 (25 nm) decreased cellular energy stores (carbohydrates, lipids, and proteins) and increased cellular energy demand (measured as the activity of the mitochondrial electron transport system, ETS). During the first 7 days, energy was supplied mainly through the consumption of carbohydrates, while lipids are mobilized to participate after 7 days. The presence of predators caused a further decrease in energy stores. These findings demonstrate that PCP, nano-TiO 2 and predators have a negative impact on energy metabolism at the cellular level. Carbohydrates are not able to meet the metabolic demand, lipids need to be consumed, and energy metabolism was also mediated by the involvement of proteins. Overall, our results suggest that PCP, nano-TiO 2 and predators disrupt the cellular energy metabolism of mussels through reduced cellular energy allocation, small particles and predators drive mussels to exert energetic metabolic adjustments for detoxification reactions when toxic contaminants are present. [Display omitted] • The presence of predators increases the effect of nano-TiO 2 and PCP on cellular energy allocation of mussel. • The presence of nano-TiO 2 exacerbates PCP energy depletion in mussels. • Nano-TiO 2 , PCP and crabs have interaction on cellular energy allocation. • Mussels generated comparable patterns of cellular energy allocation in response to two different kinds of pollutants. [ABSTRACT FROM AUTHOR]

• Prednisone and prednisoline negatively altered the thyroid and liver morphology. • Both glucocorticoids were genotoxic and affected the tadpoles' immune system. • Prednisone altered development and caused oxidative stress. • Environmental concentrations of glucocorticoids affect tadpole health. Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S -transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress. [ABSTRACT FROM AUTHOR]

Sponges are not routinely employed as metal bioindicators in Brazil. In this sense, this study reports baseline metal and metalloid concentrations, determined by inductively coupled plasma mass spectrometry, for two Demospongiae sponge species, Hymeniacidon heliophila and Desmapsamma anchorata , sampled from two Southeastern Brazil areas. Sponges from Ilha Grande Bay, an Environmental Protection Area, exhibited higher Al, As, Cd, Co, Cr, Fe, and Ni levels compared to Vermelha Beach, a metropolitan area in the Rio de Janeiro city. Several strong correlations were noted between elemental pairs, indicating common contamination sources and/or similar metabolic detoxification routes. Comparisons of the means determined herein for each study site to other reports indicate mostly lower Ag, As, Co, Cd, and Cu levels, while Al levels were higher than other studies, and Cr, Ni, and Fe were within reported ranges. These baseline data further knowledge on metal pollution in Desmspongiae members, which are still limited. [Display omitted] • Metals were determined in two marine sponges from Southeastern Brazil. • Most metals were higher in the species from an Environmental Protection Area. • Ag and Cu were higher in the species from metropolitan region of Rio de Janeiro. • Several strong correlations between metal pairs were observed. • These baseline data further knowledge on metal pollution in Demospongiae members. [ABSTRACT FROM AUTHOR]

Glutathione S -transferase (GST) is a potential therapeutic drug target against helminthic diseases. This essential enzyme prevents oxidative stress by inhibiting the toxic build-up of xenobiotics in the worm during human host infection. Schistosoma schistosome manifests two GST isoforms, namely the 26- and 28-kDa GST, which exhibit contrasting substrate specificities within the worm. This study was designed to explore the structural and functional relationships of Schistosoma bovis 28 kDa-GST (Sb28GST) through crystallographic studies. The 1-Chloro-2,4-Dinitrobenzene-Glutathione assay revealed that the enzyme was catalytically active. The secondary structural content confirmed that Sb28GST follows a canonical GST fold, mostly alpha-helical. Extrinsic 1-anilinonaphthalene-8-sulfonic acid substitution revealed buried hydrophobic clefts within the enzyme. Sb28GST was purified by immobilised metal affinity chromatography. Crystal structures of Sb28GST were determined for the un-ligated enzyme (resolution = 2.3 Å, R factor = 21.68 %). The crystals belonged to the monoclinic space group P2 1 , which accommodated two biological molecules in the asymmetric unit with the unit-cell parameters of a = 54.133, b = 77.086, c = 54.015 Å and β = 93.15° Computational modelling studies predicted the catalytic propensity of 8ALS may vary from that of 1OE8 by differences in the molecular dynamic trajectory, especially at the dimer interface of this obligate dimeric enzyme. [ABSTRACT FROM AUTHOR]

A dual-modality enzyme assay combining the fluorescence and colorimetry merits based on nanoscale metal-organic frameworks (nMOFs) was established for the analysis of glutathione S-transferase (GST). In this design, HKUST-1 with CuII metal nodes, was chosen as nMOFs and encapsulated with rhodamine 6 G (Rho 6 G) in one-step reaction to fabricate the functional nMOFs (Rho 6 G@Cu-MOFs). As a proof of concept, as a GST binding substrate, reductive glutathione (GSH) invokes competitive coordination with Cu nodes through sulfur atom as well as the valence transformation, of which the process results in coordination bond leakage and even framework collapse, leading to the releasing of internal Rho 6 G dyes for fluorescence-modality analysis. In addition, reductive GSH can interact with Cu nodes in the nMOFs and modulate CuII to CuI, along with a color change for colorimetry analysis. The dual-modality assay shows high analytical performance for GST quantification in a linear range of 0.25–100 nM with a detection limit down to 0.13 nM for fluorescence modality, and a linear range of 1–100 nM with a detection limit of 0.64 nM for colorimetry modality. In addition, the precision of the dual-modality assay shows good agreements with commercial GST activity assay kit. [Display omitted] • An enzymatic assay based on nanoscale metal-organic frameworks (nMOFs) was established for glutathione S-transferase (GST). • The dual-modality assay exhibits the independent merits of the fluorescence and colorimetry. • The dual-modality assay shows the mutual validation of dual modalities. • The nMOFs sensor exhibits accurate and sensitive detection of GST. [ABSTRACT FROM AUTHOR]

The European honey bee, Apis mellifera , serves as the principle managed pollinator species globally. In recent decades, honey bee populations have been facing serious health threats from combined biotic and abiotic stressors, including diseases, limited nutrition, and agrochemical exposure. Understanding the molecular mechanisms underlying xenobiotic adaptation of A. mellifera is critical, considering its extensive exposure to phytochemicals and agrochemicals present in the environment. In this study, we conducted a comprehensive structural and functional characterization of AmGSTD1, a delta class glutathione S-transferase (GST), to unravel its roles in agrochemical detoxification and antioxidative stress responses. We determined the 3-dimensional (3D) structure of a honey bee GST using protein crystallography for the first time, providing new insights into its molecular structure. Our investigations revealed that AmGSTD1 metabolizes model substrates, including 1-chloro-2,4-dinitrobenzene (CDNB), p -nitrophenyl acetate (PNA), phenylethyl isothiocyanate (PEITC), propyl isothiocyanate (PITC), and the oxidation byproduct 4-hydroxynonenal (HNE). Moreover, we discovered that AmGSTD1 exhibits binding affinity with the fluorophore 8-Anilinonaphthalene-1-sulfonic acid (ANS), which can be inhibited with various herbicides, fungicides, insecticides, and their metabolites. These findings highlight the potential contribution of AmGSTD1 in safeguarding honey bee health against various agrochemicals, while also mitigating oxidative stress resulting from exposure to these substances. [Display omitted] • The three-dimensional structure of AmGSTD1 was solved by X-ray crystallography. • G-site S34A and H-site F142A mutants exhibited the largest changes in kinetics. • Herbicides, fungicides, insecticides, and metabolites hindered AmGSTD1-ANS binding. • AmGSTD1 was highly expressed in the Malpighian tubules of both nurse and forager bees. [ABSTRACT FROM AUTHOR]

A novel, dual-faced, and hierarchical type of Janus hybrid structures (JHSs) was assembled through an in situ growing of lipase@cobalt phosphate sheets on the laccase@copper phosphate sponge-like structures. The chemical and structural information of prepared JHSs was investigated by Scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction analysis (XRD). The catalytic activity, storage stability, and reusability of JHSs were then investigated. The SEM-EDX analysis clearly confirmed the asymmetric morphology of the fabricated JHSs with two distinct metal distributions. Under optimized synthesis conditions, the prepared JHSs showed 97.8 % and 100 % of laccase and lipase activity, respectively. Compared to the free biocatalysts, the immobilization resulted in ~ a 2-fold increase in laccase and lipase stability at temperatures of >40 °C. The fabricated JHSs maintained 61 % and 90 % of their original laccase and lipase activity upon 12 successive repetition cycles. Up to 80 % of Reactive Blue-19 (RB-19), an anthraquinone-based vinyl sulphone dye, was removed after 5 h treatment with the prepared JHSs (50 % higher than the free forms of laccase and lipase). The dye removal data fitted very well on the pseudo-second-order kinetic model with a rate constant of 0.8 g mg−1 h−1. Following the bioremoval process, bacterial toxicity also decreased by about 70 %. Therefore, the prepared JHSs provide a facile and sustainable approach for the decolorization, biotransformation, and detoxification of RB-19 by integrating enzymatic oxidation and hydrolysis. • Enzymatic dual-faced structures were prepared by a simple, facile, and green method. • Improved stability was attributed to limited conformational changes of the enzymes. • Metal ion coordination may be the main reason for the enhanced enzymatic activity. • Firm anchor of the enzymes to hybrid structures effectively avoids their leakage. • Hydrolysis and oxidation are the essential mechanisms for the dye bioremoval. [ABSTRACT FROM AUTHOR]

Dengue fever is a worldwide public health problem, and efforts to eradicate it have focused on controlling the dengue vector, Aedes aegypti. This study aims to assess the toxicity and effect of commercial eugenol and piperine on Ae. aegypti larvae through enzyme detoxification and histopathological changes in the midgut. Laboratory-reared Ae. aegypti larvae were treated with various concentrations of commercial eugenol and piperine and observed after 24, 48, and 72 h. Biochemical methods were used to assess detoxification enzyme activity for acetylcholinesterase, glutathione S-transferase, and oxidase, and changes in the midgut were examined using routine histological examination. In terms of larvicidal activity, piperine exceeded eugenol. Piperine and eugenol had LC 50 and LC 90 values of 3.057 and 5.543 μM, respectively, and 6.421 and 44.722 μM at 24 h. Piperine and eugenol reduced oxidase activity significantly (p < 0.05), but increased acetylcholinesterase and glutathione S-transferase activity significantly (p < 0.05). After being exposed to piperine and eugenol, the food bolus and peritrophic membrane ruptured, the epithelial layer was interrupted and irregular, the epithelial cells shrank and formed irregularly, and the microvilli became irregular in shape. Commercial piperine and eugenol behave as potential larvicides, with processes involving altered detoxifying enzymes, specifically decreased oxidase function and increased GST activity, as well as midgut histological abnormalities. [Display omitted] • Eugenol and piperine kill Aedes aegypti larvae. • Inhibited oxidase. • Changed midgut. [ABSTRACT FROM AUTHOR]

Since fish metalloproteins are still not thoroughly characterized, the aim of this study was to investigate the acidic/basic nature of biomolecules involved in the sequestration of twelve selected metals in the soluble hepatic fraction of an important aquatic bioindicator organism, namely the fish species northern pike (Esox lucius). For this purpose, the hyphenated system HPLC-ICP-MS was applied, with chromatographic separation based on anion/cation-exchange principle at physiological pH (7.4). The results indicated predominant acidic nature of metal-binding peptides/proteins in the studied hepatic fraction. More than 90 % of Ag, Cd, Co, Cu, Fe, Mo, and Pb were eluted with negatively charged biomolecules, and >70 % of Bi, Mn, and Zn. Thallium was revealed to bind equally to negatively and positively charged biomolecules, and Cs predominantly to positively charged ones. The majority of acidic (negatively charged) metalloproteins/peptides were coeluted within the elution time range of applied standard proteins, having pIs clustered around 4–6. Furthermore, binding of several metals (Ag, Cd, Cu, Zn) to two MT-isoforms was assumed, with Cd and Zn preferentially bound to MT1 and Ag to MT2, and Cu evenly distributed between the two. The results presented here are the first of their kind for the important bioindicator species, the northern pike, as well as one of the rare comprehensive studies on the acidic/basic nature of metal-binding biomolecules in fish, which can contribute significantly to a better understanding of the behaviour and fate of metals in the fish organism, specifically in liver as main metabolic and detoxification organ. • Important new contribution to better understanding of metal behaviour/fate in fish • Predominant acidic nature of cytosolic metalloproteins in the northern pike liver • Tl and Cs notably bound to basic biomolecules • Ag, Cd, Cu, and Zn presumably bound to two MT-isoforms • Cd/Zn preferentially bound to MT1, Ag to MT2, Cu evenly distributed between the two [ABSTRACT FROM AUTHOR]

[Display omitted] • SSC influences the microscopic morphology of BiOCl. • Thin-sheet like structure enhances the absorption of light. • Level of OVs has been promoted. • Photogenerated charge pairs separation efficiency has been boosted. In this work, a one-pot hydrothermal method was employed to fabricate sorghum straw carbon (SSC) modified BiOCl catalysts. SSC not only operates as a template agent to regulate the microscopic morphology of BiOCl to form thinner lamellar structures but also constructs oxygen vacancies (OVs), which together enhance the photocatalytic ability. The samples were researched by Brunauer-Emmett-Teller (BET), X-ray diffractometer (XRD) and scanning electron microscope (SEM). Addition of SSC induce BiOCl to form a flower spherical-like structure assembled by thin sheets. Surface photovoltage spectroscopy (SPS) and electrochemical experiments confirm that the dense interlayer stacking provides more pathways for the separation of charges from bulk to the surface, and the thinner sheet thickness shortens the separation time for the charges, boosting the activity of the photocatalysts. The existence of the main reactive radicals (O 2 – and h+) in the photocatalytic system was investigated by trapping experiments. Photocatalytic activity of the samples was assessed by destruction of rhodamine B (RhB), tetracycline (TC) and perfluorooctanoic acid (PFOA). When the mass ratio of SSC/BiOCl is 0.75%, the catalyst shows the best photocatalytic activity. A reasonable photocatalytic enhancement mechanism was proposed in combination with the observation results. [ABSTRACT FROM AUTHOR]

[Display omitted] • PPL is immobilized in the mesopores of Fe 3 O 4 @HMUiO-66-NH 2 without cross-linking agent. • PPL/Fe 3 O 4 @HMUiO-66-NH 2 has a good stability, reusability, and biocompatibility. • PPL/Fe 3 O 4 @HMUiO-66-NH 2 exhibits an enhanced enzyme loading, enzyme activity, and PAT detoxification rate. • PPL/Fe 3 O 4 @HMUiO-66-NH 2 can detoxify PAT from apple juice. Patulin (PAT) is a mycotoxin known to globally contaminate fruits. The economic losses and health hazards caused by PAT desires a safe and efficient strategy for detoxifying PAT. Here, a magnetic core–shell hierarchical mesoporous metal–organic framework (Fe 3 O 4 @HMUiO-66-NH 2) was synthesized via a salt-assisted nanoemulsion guided assembly method. This mesoporous structure (centered at 4.25 nm) allowed porcine pancreatic lipase (PPL) to infiltrate into the MOF shell at an immobilized amount of 255 mg/g, providing protection for PPL and enabling rapid separation and recovery. Compared with free PPL, PPL/Fe 3 O 4 @HMUiO-66-NH 2 at 70 °C possessed 4.7 folds improved thermal stability in terms of half-life. The detoxification rates of immobilized enzyme for PAT in neutral water, acidic water, and apple juice were 99.6%, 60.9%, and 52.6%, respectively. Moreover, the so designed PPL/Fe 3 O 4 @HMUiO-66-NH 2 showed extraordinary storage stability, reusability, and biocompatibility. Crucially, the quality of apple juice did not change significantly after PPL/Fe 3 O 4 @HMUiO-66-NH 2 treatment, which facilitated its application in apple juice. The magnetic core–shell mesoporous structure along with the revealed mechanism of immobilized enzyme detoxification of PAT provide tremendous opportunity for designing a safe and efficient PAT detoxification method. [ABSTRACT FROM AUTHOR]

• Cellular homeostasis of blood clam was notably disrupted by 20 and 200 μg/L of TCS • Two concentrations of TCS hampered cellular and humoral immunity of blood clam • TCS at two designed levels suppressed metabolism and energy supply of blood clam • Inhibited detoxification upon TCS exposure led to TCS accumulation in blood clam Omnipresent presence of triclosan (TCS) in aqueous environment puts a potential threat to organisms. However, it's poorly understood about its immunometabolic impacts of marine invertebrates. In present study, we use a representative bivalve blood clam (Tegillarca granosa) as a model, investigating the effects of TCS exposure at 20 and 200 μg/L for 28 days on immunometabolism, detoxification, and cellular homeostasis to explore feasible toxicity mechanisms. Results demonstrated that the clams exposed to TCS resulting in evident immunotoxic impacts on both cellular and humoral immune responses, through shifting metabolic pathways and substances, as well as suppressing the expressions of genes from the immune– and metabolism–related pathways. In addition, significant alterations in contents (or activity) of detoxification enzymes and the expression of key detoxification genes were detected in TCS-exposed clams. Moreover, exposure to TCS also disrupted cellular homeostasis of clams through increasing MDA contents and caspase activities, and promoting activation of the apoptosis–related genes. These findings suggested that TCS might induce immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis. [Display omitted] [ABSTRACT FROM AUTHOR]