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Hardly anything is known regarding the detoxification of surfactants in crop plants, although they are frequently treated with agrochemical formulations. Therefore, we studied transcriptomic changes in barley leaves induced in response to spraying leaf surfaces with two alcohol ethoxylates (AEs). As model surfactants, we selected the monodisperse tetraethylene glycol monododecyl (C12E4) ether and the polydisperse BrijL4. Barley plants were harvested 8 h after spraying with a 0.1% surfactant solution and changes in gene expression were analysed by RNA-sequencing (RNA-Seq). Gene expression was significantly altered in response to both surfactants. With BrijL4 more genes (9724) were differentially expressed compared to C12E4 (6197). Gene families showing pronounced up-regulation were cytochrome P450 enzymes, monooxygenases, ABC-transporters, acetyl- and methyl- transferases, glutathione-S-transferases and glycosyltransferases. These specific changes in gene expression and the postulated function of the corresponding enzymes allowed hypothesizing three potential metabolic pathways of AE detoxification in barley leaves. (i) Up-regulation of P450 cytochrome oxidoreductases suggested a degradation of the lipophilic alkyl residue (dodecyl chain) of the AEs by ω- and β- oxidation. (ii) Alternatively, the polar PEG-chain of AEs could be degraded. (iii) Instead of surfactant degradation, a further pathway of detoxification could be the sequestration of AEs into the vacuole or the apoplast (cell wall). Thus, our results show that AEs lead to pronounced changes in the expression of genes coding for proteins potentially being involved in the detoxification of surfactants. [ABSTRACT FROM AUTHOR]

A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss‐or‐gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid‐β aggregation. Based on this, we reveal that a hidden peptide ("cryptide")—AbaPep#07 (SETYELRK)—derived from abalone hemocyanin not only enhances survival resilience against paraquat‐induced oxidative stress but also rescues proteotoxicity‐mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost‐free longevity and age‐related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN‐1/Nrf, but not DAF‐16/FOXO, transcription factor. In contrast to its effects in wild‐type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss‐of‐function skn‐1 mutant, suggesting an SKN‐1/Nrf‐dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN‐1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN‐1/Nrf‐governed transcriptional reprogramming, and provide an insight into the health‐promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions. [ABSTRACT FROM AUTHOR]

The present work deals with simple hydrothermal preparation of magnetically separable BiVO4/N-rGO/CuFe2O4 Z-scheme hybrid photocatalyst for efficient detoxification of p-bromophenol (p-BP). BiVO4 is one of the most efficient visible light catalyst, however, suffers with photo-corrosion and high recombination of charge carriers that restricts its applications. Addition of graphene oxide doped with nitrogen are believed to overcome these issues. Further addition of CuFe2O4 enhances the catalytic degradation and helps in separating the catalyst. With these merits BiVO4/N-rGO/CuFe2O4 could be a promising photocatalyst for detoxification of p-BP. After 60 min of irradiation 94.1 ± 1.2% degradation was achieved by the BiVO4/N-rGO/CuFe2O4 (k = 0.01749 min−1) while only 53.8 ± 2.3% was observed in BiVO4 (k = 0.00674 min−1). The catalyst could be able to recover using external magnet and showed 86.4% of degradation efficiency even after five recycles, which suggested its good stability. The degradation products identification and pathway were proposed based on LC-ESI/MS analysis. Moreover, phytotoxicity assessment of the degradation products was investigated on Phaseolus vulgaris in which the germination index (GI) was about 11.4% for pure p-BP, while it was about 83.03% for degradation products. Thus, the results suggested that more efficient p-BP detoxification was achieved during this photodegradation. [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]

Introduction: We evaluated the effect of Tucum-do-Cerrado on glucose metabolism homeostasis and its relationship with redox-inflammatory responses in a high-fat (HF) diet-induced obesity model. Results: The HF diet increased energy intake, feed efficiency, body weight, muscle and hepatic glycogen, insulin, homeostatic model assessment of insulin resistance (HOMA IR) and beta (β)-cell function, and gut catalase (CAT) activity, and decreased food intake, hepatic glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD) activities, hepatic phosphoenolpyruvate carboxykinase 1 (Pck1), and intestinal solute carrier family 5 member 1 (Slc5a1) mRNA levels compared with the control diet. However, the HF diet with Tucum-do-Cerrado decreased hepatic glycogen, and increased hepatic GR activity, hepatic Slc2a2 mRNA levels and serum Tnfa compared with the HF diet. Tucum-do-Cerrado decreased muscle glycogen, intestinal CAT and GPX activities, muscle PFK-1 and HK activities, and increased hepatic protein (CARB) and intestinal lipid (MDA) oxidation, hepatic GST activity, serum antioxidant potential, hepatic phosphofructokinase-1 (PFK-1) activity, intestinal solute carrier family 2 member 2 (Slc2a2), tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), muscle protein kinase AMP-activated alpha 1 (Prkaa1), solute carrier family 2 member 2 (Slc2a2) mRNA levels, and serum interleukin-6 (IL-6) levels, regardless of diet type. Conclusion: Tucum-do-Cerrado consumption may ameliorate impaired glucose utilization in a HF diet-induced obesity model by increasing liver and muscle glucose uptake and oxidation. These data suggest that Tucum-do-Cerrado consumption improves muscle glucose oxidation in non-obese and obese rats. This response may be related to the improvement in the total antioxidant capacity of rats. [ABSTRACT FROM AUTHOR]

Uridine 5′-diphospho-glucuronosyltransferases (UGTs) have been considered as a family of enzymes responsible for the glucuronidation process, a crucial phase II detoxification reaction. Among the various UGT isoforms, UGTs A10 and B7 have garnered significant attention due to their broad substrate specificity and involvement in the metabolism of numerous compounds. Recent studies have suggested that certain vitamins may exert inhibitory effects on UGT activity, thereby influencing the metabolism of drugs, environmental toxins, and endogenous substances, ultimately impacting their biological activities. In the present study, the inhibition potential of vitamins (A, B1, B2, B3, B5, B6, B7, B9, D3, E, and C) on UGT1A10 and UGT2B7 was determined using in silico and in vitro approaches. A 3-dimensional model of UGT1A10 and UGT2B7 enzymes was built using Swiss Model, ITASSER, and ROSETTA and verified using Ramachandran plot and SAVES tools. Molecular docking studies revealed that vitamins interact with UGT1A10 and UGT2B7 enzymes by binding within the active site pocket and interacting with residues. Among all vitamins, the highest binding affinity predicted by molecular docking was − 8.61 kcal/mol with vitamin B1. The in vitro studies results demonstrated the inhibition of the glucuronidation activity of UGTs by vitamins A, B1, B2, B6, B9, C, D, and E, with IC50 values of 3.28 ± 1.07 µg/mL, 24.21 ± 1.11 µg/mL, 3.69 ± 1.02 µg/mL, 23.60 ± 1.08 µg/mL, 6.77 ± 1.08 µg/mL, 83.95 ± 1.09 µg/ml, 3.27 ± 1.13 µg/mL and 3.89 ± 1.12 µg/mL, respectively. These studies provided the valuable insights into the mechanisms underlying drug-vitamins interactions and have the potential to guide personalized medicine approaches, optimizing therapeutic outcomes, and ensuring patient safety. Indeed, further research in the area of UGT (UDP-glucuronosyltransferase) inhibition by vitamins is essential to fully understand the clinical relevance and implications of these interactions. UGTs play a crucial role in the metabolism and elimination of various drugs, toxins, and endogenous compounds in the body. Therefore, any factors that can modulate UGT activity, including vitamins, can have implications for drug metabolism, drug-drug interactions, and overall health. [ABSTRACT FROM AUTHOR]

Background: The liver serves as a vital organ in metabolic processes and detoxification, making it susceptible to damage induced by xenobiotics such as drugs. Paracetamol overdose is a common cause of hepatotoxicity. Traditional medicine has long explored botanical sources for hepatoprotective agents, highlighting the potential of natural compounds in mitigating liver damage. Lemon peel, rich in flavonoids with antioxidant properties, presents a promising candidate for hepatoprotection. Materials and Methods: This study aimed to investigate the hepatoprotective effects of lemon peel extract on paracetamol-induced liver toxicity in rats. The extract was prepared through standardized extraction procedures and its dose was selected based on previous studies. Wistar rats were divided into five groups and subjected to various treatments, including paracetamol overdose with or without lemon peel extract supplementation. Biochemical parameters indicative of liver function, such as serum levels of AST, ALT, ALP and bilirubin, were measured following treatment protocols. Results: Administration of paracetamol alone induced significant elevation in serum levels of AST, ALT, ALP and bilirubin, reflecting hepatocellular damage. However, co-administration of lemon peel extract with paracetamol resulted in reduced levels of these biochemical markers compared to the paracetamol-only group. The decrease in enzyme levels suggests potential hepatoprotective effects of lemon peel extract. Conclusion: Lemon peel extract demonstrated hepatoprotective effects against paracetamol-induced liver toxicity in rats, as evidenced by the attenuation of biochemical markers indicative of liver damage. These findings highlight the therapeutic potential of lemon peel extract as a natural remedy for protecting liver health and mitigating the adverse effects of hepatotoxic agents. [ABSTRACT FROM AUTHOR]

Background and aims: Cadmium (Cd) contamination poses a potential threat to plant growth and human health. In this study, we aimed to determine the effect of selenium nanoparticles (SeNPs) on Cd and selenium (Se) uptake and accumulation in bok choy, and investigate the detoxification mechanism of SeNPs on bok choy under Cd stress. Methods: A pot culture was performed in Cd–contaminated soil with soil applied and foliar–sprayed SeNPs, including SLow, SHigh, FLow, FHigh, and corresponding control treatment. The soil available Cd content, Cd and Se fractions in soil, elements accumulation, subcellular Cd/Se distribution, MDA content, SOD activity, and Fourier transformed infrared spectroscopy (FTIR) were evaluated. Results: Soil applied SeNPs significantly reduced Cd concentration by 25.9–42.4%, and Cd uptake rate by 33.4–37.8%. Further, soil applied SeNPs had no significant effect on available Cd but did affect Se fractions in soil. Additionally, soil applied SeNPs increased Se concentration by 3.1 − 6.3 times in bok choy and caused a higher Se concentration in root than in shoot, with the residual and organic matter–bound Se mainly affecting Se accumulation in shoot. However, foliar–sprayed SeNPs had no significant effect on Cd uptake but increased Se accumulation by 2.4 − 33.0 times in bok choy. Soil applied and foliar–sprayed SeNPs prompted the distribution of Cd in cell wall and in soluble component in shoot, respectively, which reduced the damage of Cd on organelle. Conclusion: Soil applied SeNPs was an effective method for reducing Cd accumulation and improving Se biofortification and mineral elements accumulation in bok choy. [ABSTRACT FROM AUTHOR]

Shading is an important technique to protect tea plantations under abiotic stresses. In this study, we analyzed the effect of shading (SD60% shade vs. SD0% no-shade) on the physiological attributes and proteomic analysis of tea leaves in November and December during low temperatures. The results revealed that shading protected the tea plants, including their soil plant analysis development (SPAD), photochemical efficiency (Fv/Fm), and nitrogen content (N), in November and December. The proteomics analysis of tea leaves was determined using tandem mass tags (TMT) technology and a total of 7263 proteins were accumulated. Further, statistical analysis and the fold change of significant proteins (FC < 0.67 and FC > 1.5 p < 0.05) revealed 14 DAPs, 11 increased and 3 decreased, in November (nCK_vs_nSD60), 20 DAPs, 7 increased and 13 decreased, in December (dCK_vs_dSD60), and 12 DAPs, 3 increased and 9 decreased, in both November and December (nCK_vs_nSD60). These differentially accumulated proteins (DAPs) were dehydrins (DHNs), late-embryogenesis abundant (LEA), thaumatin-like proteins (TLPs), glutathione S-transferase (GSTs), gibberellin-regulated proteins (GAs), proline-rich proteins (PRPs), cold and drought proteins (CORA-like), and early light-induced protein 1, which were found in the cytoplasm, nucleus, chloroplast, extra cell, and plasma membrane, and functioned in catalytic, cellular, stimulus-response, and metabolic pathways. In conclusion, the proliferation of key proteins was triggered by translation and posttranslational modifications, which might sustain membrane permeability in tea cellular compartments and could be responsible for tea protection under shading during low temperatures. This study aimed to investigate the impact of the conventional breeding technique (shading) and modern molecular technologies (proteomics) on tea plants, for the development and protection of new tea cultivars. [ABSTRACT FROM AUTHOR]

Ecological theories suggest that environmental factors significantly influence obesity risk and related syndemic morbidities, including metabolically abnormal obesity associated with nonalcoholic fatty liver disease (MASLD). These factors encompass anthropogenic influences and endocrine-disrupting chemicals (EDCs), synergistically interacting to induce metabolic discrepancies, notably in early life, and disrupt metabolic processes in adulthood. This review focuses on endocrine disruptors affecting a child's MASLD risk, independent of their role as obesogens and thus regardless of their impact on adipogenesis. The liver plays a pivotal role in metabolic and detoxification processes, where various lipophilic endocrine-disrupting molecules accumulate in fatty liver parenchyma, exacerbating inflammation and functioning as new anthropogenics that perpetuate chronic low-grade inflammation, especially insulin resistance, crucial in the pathogenesis of MASLD. [ABSTRACT FROM AUTHOR]

Auxin‐mimic herbicides chemically mimic the phytohormone indole‐3‐acetic‐acid (IAA). Within the auxin‐mimic herbicide class, the herbicide fluroxypyr has been extensively used to control kochia (Bassia scoparia). A 2014 field survey for herbicide resistance in kochia populations across Colorado identified a putative fluroxypyr‐resistant (Flur‐R) population that was assessed for response to fluroxypyr and dicamba (auxin‐mimics), atrazine (photosystem II inhibitor), glyphosate (EPSPS inhibitor), and chlorsulfuron (acetolactate synthase inhibitor). This population was resistant to fluroxypyr and chlorsulfuron but sensitive to glyphosate, atrazine, and dicamba. Subsequent dose‐response studies determined that Flur‐R was 40 times more resistant to fluroxypyr than a susceptible population (J01‐S) collected from the same field survey (LD50 720 and 20 g ae ha−1, respectively). Auxin‐responsive gene expression increased following fluroxypyr treatment in Flur‐R, J01‐S, and in a dicamba‐resistant, fluroxypyr‐susceptible line 9,425 in an RNA‐sequencing experiment. In Flur‐R, several transcripts with molecular functions for conjugation and transport were constitutively higher expressed, such as glutathione S‐transferases (GSTs), UDP‐glucosyl transferase (GT), and ATP binding cassette transporters (ABC transporters). After analyzing metabolic profiles over time, both Flur‐R and J01‐S rapidly converted [14C]‐fluroxypyr ester, the herbicide formulation applied to plants, to [14C]‐fluroxypyr acid, the biologically active form of the herbicide, and three unknown metabolites. The formation and flux of these metabolites were faster in Flur‐R than J01‐S, reducing the concentration of phytotoxic fluroxypyr acid. One unique metabolite was present in Flur‐R that was not present in the J01‐S metabolic profile. Gene sequence variant analysis specifically for auxin receptor and signaling proteins revealed the absence of non‐synonymous mutations affecting auxin signaling and binding in candidate auxin target site genes, further supporting our hypothesis that non‐target site metabolic degradation is contributing to fluroxypyr resistance in Flur‐R. Significance Statement: Herbicide resistance is an ever‐present issue in weeds of cropping and rangeland systems. Every characterized herbicide resistance mechanism contributes to a working database used to address herbicide resistance in an agricultural or open‐space setting. Knowing the exact resistance mechanism helps public sector and industry researchers understand why herbicide applications are failing, and if resistant plants can still be controlled with other herbicide modes of action. In the kochia line Flur‐R, there is strong evidence to support a non‐target site resistance mechanism, specifically herbicide degradation via increased enzymatic activity. Increased fluroxypyr degradation represents a novel resistance mechanism to fluroxypyr in Bassia scoparia. [ABSTRACT FROM AUTHOR]

The bark beetle, Ips typographus (L.), is a major pest of Norway spruce, Picea abies (L.), causing enormous economic losses globally. The adult stage of the I. typographus has a complex life cycle (callow and sclerotized); the callow beetles feed ferociously, whereas sclerotized male beetles are more aggressive and pioneers in establishing new colonies. We conducted a comparative proteomics study to understand male and female digestion and detoxification processes in callow and sclerotized beetles. Proteome profiling was performed using high-throughput liquid chromatography-mass spectrometry. A total of >3000 proteins were identified from the bark beetle gut, and among them, 539 were differentially abundant (fold change ±2, FDR <0.05) between callow and sclerotized beetles. The differentially abundant proteins (DAPs) mainly engage with binding, catalytic activity, anatomical activity, hydrolase activity, metabolic process, and carbohydrate metabolism, and hence may be crucial for growth, digestion, detoxification, and signalling. We validated selected DAPs with RTqPCR. Gut enzymes such as NADPH-cytochrome P450 reductase (CYC), glutathione S-transferase (GST), and esterase (EST) play a crucial role in the I. typographus for detoxification and digesting of host allelochemicals. We conducted enzyme activity assays with them and observed a positive correlation of CYC and GST activities with the proteomic results, whereas EST activity was not fully correlated. Furthermore, our investigation revealed that callow beetles had an upregulation of proteins associated with juvenile hormone (JH) biosynthesis and chitin metabolism, whereas sclerotized beetles exhibited an upregulation of proteins linked to fatty acid metabolism and the TCA cycle. These distinctive patterns of protein regulation in metabolic and functional processes are specific to each developmental stage, underscoring the adaptive responses of I. typographicus in overcoming conifer defences and facilitating their survival. Taken together, it is the first gut proteomic study comparing males and females of callow and sclerotized I. typographus, shedding light on the adaptive ecology at the molecular level. Furthermore, the information about bark beetle handling of nutritionally limiting and defence-rich spruce phloem diet can be utilized to formulate RNAi-mediated beetle management. [ABSTRACT FROM AUTHOR]

The sustainability of aquaculture is subject to environmental changes, such as changes in temperature, which affect the physiological homeostasis of fish. Thermal shock (natural or anthropogenic) is a stress condition that results in a sequence of physiological responses and even mortality. Considering the impact of sudden reductions in temperature on the biological systems and that this occurrence is common in regions where pacu (Piaractus mesopotamicus) is farmed, we evaluated the stress, immune, and antioxidant responses of the species exposed to temperature drop. Two groups of fish were exposed to 28 °C or 16 °C for 24 h, and then fish were kept at 28 °C to recover and be sampled: before the temperature drop (baseline); after 24 h of cold exposure; and 3, 8, and 24 h after the return to 28 °C (recovery). The exposure of pacu to 16 °C did not alter the stress biomarkers after 24 h, but it activated the innate immune system (leukocyte respiratory activity, hemolytic activity of the complement system, and serum lysozyme concentration). It also promoted oxidative stress without altering most of the antioxidant system indicators, except for an initial reduction of glutathione peroxidase (GPx) activity after exposure to 16 °C and a late activation, besides the late activation of glutathione transferase (GST), probably as a compensatory process to reduce tissue damage. Pacu was sensitive to temperature changes, but it was able to activate immune and compensatory responses to mitigate oxidative stress. The results will help producers in the management of pacu during periods of thermal changes, such as in autumn and winter. [ABSTRACT FROM AUTHOR]

Acrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were exposed to air (0 ppm) or acrolein (3.16 ppm) for 4 h, followed by immediate serum and liver tissue collection. Serum metabolomics in both sexes and liver transcriptomics in males were evaluated to characterize the systemic metabolic response. Of 887 identified metabolites, > 400 differed between sexes at baseline. An acrolein biomarker, 3-hydroxypropyl mercapturic acid, increased 18-fold in males and 33-fold in females, indicating greater metabolic detoxification in females than males. Acrolein exposure changed 174 metabolites in males but only 50 in females. Metabolic process assessment identified higher circulating free-fatty acids, glycerols, and other lipids in male but not female rats exposed to acrolein. In males, acrolein also increased branched-chain amino acids, which was linked with metabolites of nitrogen imbalance within the gut microbiome. The contribution of neuroendocrine stress was evident by increased corticosterone in males but not females. Male liver transcriptomics revealed acrolein-induced over-representation of lipid and protein metabolic processes, and pathway alterations including Sirtuin, insulin-receptor, acute-phase, and glucocorticoid signaling. In sum, acute acrolein inhalation resulted in sex-specific serum metabolomic and liver transcriptomic derangement, which may have connections to chronic metabolic-related diseases. [ABSTRACT FROM AUTHOR]

UDP‐glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that play important roles in the detoxification of endogenous and exogenous substrates. The 22 human UGTs belong to four families (UGT1, UGT2, UGT3, and UGT8) and differ in their expression, substrate specificity, UDP‐sugar preference, and physiological functions. Differential expression/activity of the UGTs contributes to interperson variability in drug responses and toxicity, hormone homeostasis, and disease/cancer risks. However, in normal tissues, the tissue‐specific expression profiles and transcriptional regulation of the UGTs are still not fully understood. In this study, we comprehensively analyzed the transcriptome of 22 UGTs in 54 human tissues/regions using RNAseq data from GTEx. We then validated the findings in the liver and small intestine samples using real‐time PCR. Our results showed large interindividual variability across tissues in the expression of each UGT and the overall composition of UGT pools, consisting of different UGTs and their splice isoforms. Our results also revealed coexpression of the UGTs, Cytochrome P450s, and many transcription factors in the liver, suggesting potential coregulation or functional coordination. Our results provide the groundwork for future studies to detail further the regulation of the expression and activity of the UGTs. [ABSTRACT FROM AUTHOR]

The purpose of the research was to illustrate the effects of feeding Nile tilapia fingerlings (Oreochromis niloticus) with low doses of aflatoxins (AFs) with and without vitamin C supplementation to investigate the capacity of vitamin C in detoxification. Ten experimental diets were formulated and divided into three categories. The first category included: T1, T4 and T7 feedings included 20, 40 and 80 μg AFs kg−1 feed respectively, while both the second category T2, T5 and T8 and the third category T3, T6 and T9 were treated with contaminated feed with AFs for 57days then both categories shifted to different regime till the conclusion of the experimentation. The second category was fed uncontaminated feed while the third category was fed a supplemented diet with 100 mg Kg-1 of vitamin C. For 113 days the experiment was conducted. The results showed that shifting from a contaminated diet to an uncontaminated diet (category 2) or adding vitamin C to the contaminated diet (category 3) improved the deterioration that occurred in the values of growth performance, biochemical parameters and histological disorders caused by AFs. Furthermore, the results from the control group were superior to all the treatments. [ABSTRACT FROM AUTHOR]

SIRT5 and PRDx1 play crucial roles in cancer and are involved in the basic mechanisms of reactive oxygen species detoxification. In our previous studies, we showed that hemolymph extracts of immune-challenged Bombyx mori have antioxidant properties. Following H2O2 stimulation, immune-challenged B. mori hemolymph extracts elicited SIRT5 downregulation activity, reaching effective activity at the highest concentration of 100 ppm. Additionally, cells treated with immune-challenged B. mori hemolymph extracts demonstrated increased PRDx1 mRNA expression compared to that of PBS-treated cells. Therefore, immune-challenged B. mori hemolymph extracts offer a potential auxiliary means of treating drug-resistant tumors through downregulation of SIRT5 and upregulation of PRDx1 expression. Nevertheless, further studies on the effects of B. mori hemolymph on SIRT5 and PRDx1 regulation are pertinent for using it as a food or pharmaceutical material and understanding its therapeutic effect on tumors, including those that are drug-resistant. [ABSTRACT FROM AUTHOR]

Therapeutic enzymes present excellent opportunities for the treatment of human disease, modulation of metabolic pathways and system detoxification. However, current use of enzyme therapy in the clinic is limited as naturally occurring enzymes are seldom optimal for such applications and require substantial improvement by protein engineering. Engineering strategies such as design and directed evolution that have been successfully implemented for industrial biocatalysis can significantly advance the field of therapeutic enzymes, leading to biocatalysts with new‐to‐nature therapeutic activities, high selectivity, and suitability for medical applications. This minireview highlights case studies of how state‐of‐the‐art and emerging methods in protein engineering are explored for the generation of therapeutic enzymes and discusses gaps and future opportunities in the field of enzyme therapy. [ABSTRACT FROM AUTHOR]

Background: The deep-sea snail Phymorhynchus buccinoides belongs to the genus Phymorhynchus (Neogastropoda: Raphitomidae), and it is a dominant specie in the cold seep habitat. As the environment of the cold seep is characterized by darkness, hypoxia and high concentrations of toxic substances such as hydrogen sulfide (H2S), exploration of the diverse fauna living around cold seeps will help to uncover the adaptive mechanisms to this unique habitat. In the present study, a chromosome-level genome of P. buccinoides was constructed and a series of genomic and transcriptomic analyses were conducted to explore its molecular adaptation mechanisms to the cold seep environments. Results: The assembled genome size of the P. buccinoides was approximately 2.1 Gb, which is larger than most of the reported snail genomes, possibly due to the high proportion of repetitive elements. About 92.0% of the assembled base pairs of contigs were anchored to 34 pseudo‐chromosomes with a scaffold N50 size of 60.0 Mb. Compared with relative specie in the shallow water, the glutamate regulative and related genes were expanded in P. buccinoides, which contributes to the acclimation to hypoxia and coldness. Besides, the relatively high mRNA expression levels of the olfactory/chemosensory genes in osphradium indicate that P. buccinoides might have evolved a highly developed and sensitive olfactory organ for its orientation and predation. Moreover, the genome and transcriptome analyses demonstrate that P. buccinoides has evolved a sulfite-tolerance mechanism by performing H2S detoxification. Many genes involved in H2S detoxification were highly expressed in ctenidium and hepatopancreas, suggesting that these tissues might be critical for H2S detoxification and sulfite tolerance. Conclusions: In summary, our report of this chromosome-level deep-sea snail genome provides a comprehensive genomic basis for the understanding of the adaptation strategy of P. buccinoides to the extreme environment at the deep-sea cold seeps. [ABSTRACT FROM AUTHOR]

Sodium pentachlorophenol (PCP-Na) is widespread in the marine environment; however, its impact on marine organisms remains under-researched. Moerella iridescens and Exopalaemon carinicauda are marine species of economic importance in China and under threat from PCP-Na pollution. Thus, this study aimed to assess the toxicity and detoxification metabolism of PCP-Na on M. iridescens and E. carinicauda. The study revealed that the 96 h median lethal concentration (LC50) of PCP-Na for M. iridescens and E. carinicauda were 9.895 mg/L and 14.143 mg/L, respectively. A species sensitivity distribution (SSD) for PCP-Na was developed specifically for marine organisms, determining a hazardous concentration to 5% of the species (HC5) of 0.047 mg/L. During the sub-chronic exposure period, PCP-Na accumulated significantly in M. iridescens and E. carinicauda, with highest concentrations of 41.22 mg/kg in the soft tissues of M. iridescens, 42.58 mg/kg in the hepatopancreas of E. carinicauda, and only 0.85 mg/kg in the muscle of E. carinicauda. Furthermore, the study demonstrated that detoxifying metabolic enzymes and antioxidant defense system enzymes of E. carinicauda responded stronger to PCP-Na compared to M. iridescens, suggesting that E. carinicauda may possess a stronger detoxification capacity. Notably, five biomarkers were identified and proposed for monitoring and evaluating PCP-Na contamination. Overall, the results indicated that M. iridescens and E. carinicauda exhibit greater tolerance to PCP-Na than other marine species, but they are susceptible to accumulating PCP-Na in their tissues, posing a significant health risk. Consequently, conducting aquatic health risk assessments in areas with potential PCP-Na contamination is strongly recommended. [ABSTRACT FROM AUTHOR]

Chemical warfare agents (CWAs) still threaten society and have been used in recent terrorist attacks. Various adsorbents have been developed to remove CWA droplets effectively from contaminated objects to protect against serious injury. In this project, a collection of textiles, zirconium hydroxide (ZH) combined with polyvinyl alcohol (PVA)-polyethylene glycol (PEG) or polyacrylonitrile (PAN), were prepared using electro-spinning. Results of scanning electron microscopy, X-ray diffraction and inductively coupled plasma optical emission spectroscopy indicated that ZH was uniformly distributed and attached in the interstices of the polymer fiber with a high Zr load ratio of >24%. The wetting and absorption of ZH textiles to simulation agents such as 2-chloroethyl ethyl sulfide and dimethyl methylphosphate showed good performance in terms of absorption. The calculation results, where the absorption factor ka of each textile was a constant value, suggested they had excellent capacity of removing CWA droplets, such as bis(2-chloroethyl) sulfide (HD), S-2-(diisopropylamino) ethyl O-ethyl methylphosphonothioate (VX) and pinacolyl methylphosphonofluoridate (GD). The detoxification experiment showed that both textiles of ZH@PAN and PAN had optimum degradation of HD with half-lives of 84.5 min due to its fast natural hydrolysis of HD and good adsorption of HD on textile. For degradation of VX solution, ZH@PVA-PEG presented a strong degradation capability with an almost equal half-life of 64.5 min to ZH. ZH@PVA-PEG could also catalyze GD hydrolysis effectively with a half-life of 55.0 min. This work manifested the possibility for quick absorption of CWAs from contaminated objects with non-powder materials and a strong degradation ability. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is a ubiquitous tripeptide that is biosynthesized in situ at high concentrations (1–5 mM) and involved in the regulation of cellular homeostasis via multiple mechanisms. The main known action of GSH is its antioxidant capacity, which aids in maintaining the redox cycle of cells. To this end, GSH peroxidases contribute to the scavenging of various forms of ROS and RNS. A generally underestimated mechanism of action of GSH is its direct nucleophilic interaction with electrophilic compounds yielding thioether GSH S-conjugates. Many compounds, including xenobiotics (such as NAPQI, simvastatin, cisplatin, and barbital) and intrinsic compounds (such as menadione, leukotrienes, prostaglandins, and dopamine), form covalent adducts with GSH leading mainly to their detoxification. In the present article, we wish to present the key role and significance of GSH in cellular redox biology. This includes an update on the formation of GSH-S conjugates or GSH adducts with emphasis given to the mechanism of reaction, the dependence on GST (GSH S-transferase), where this conjugation occurs in tissues, and its significance. The uncovering of the GSH adducts' formation enhances our knowledge of the human metabolome. GSH–hematin adducts were recently shown to have been formed spontaneously in multiples isomers at hemolysates, leading to structural destabilization of the endogenous toxin, hematin (free heme), which is derived from the released hemoglobin. Moreover, hemin (the form of oxidized heme) has been found to act through the Kelch-like ECH associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway as an epigenetic modulator of GSH metabolism. Last but not least, the implications of the genetic defects in GSH metabolism, recorded in hemolytic syndromes, cancer and other pathologies, are presented and discussed under the framework of conceptualizing that GSH S-conjugates could be regarded as signatures of the cellular metabolism in the diseased state. [ABSTRACT FROM AUTHOR]

Heavy metals, including mercury, are non-biodegradable and highly toxic to microorganisms even at low concentrations. Understanding the mechanisms underlying the environmental adaptability of microorganisms with Hg resistance holds promise for their use in Hg bioremediation. We characterized GbsMerA, a mercury reductase belonging to the mercury-resistant operon of Gelidibacter salicanalis PAMC21136, and found its maximum activity of 474.7 µmol/min/mg in reducing Hg+2. In the presence of Ag and Mn, the enzyme exhibited moderate activity as 236.5 µmol/min/mg and 69 µmol/min/mg, respectively. GbsMerA exhibited optimal activity at pH 7.0 and a temperature of 60 °C. Moreover, the crystal structure of GbsMerA and structural comparison with homologues indicated that GbsMerA contains residues, Tyr437´ and Asp47, which may be responsible for metal transfer at the si-face by providing a hydroxyl group (−OH) to abstract a proton from the thiol group of cysteine. The complex structure with NADPH indicated that Y174 in the re-face can change its side chain direction upon NADPH binding, indicating that Y174 may have a role as a gate for NADPH binding. Moreover, the heterologous host expressing GbsMerA (pGbsMerA) is more resistant to Hg toxicity when compared to the host lacking GbsMerA. Overall, this study provides a background for understanding the catalytic mechanism and Hg detoxification by GbsMerA and suggests the application of genetically engineered E. coli strains for environmental Hg removal. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (B[a]P), one typical environmental pollutant, the toxicity mechanisms, and potential prevention remain perplexing. Available evidence suggests cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GSTs) metabolize B[a]P, resulting in metabolic activation and detoxification of B[a]P. This study aimed to reveal the impact of B[a]P exposure on trans-7,8-diol-anti-9,10-epoxide DNA (BPDE-DNA) adduct formation, level of CYP1A1, glutathione S-transferase pi (GSTP1) and glutathione S-transferase mu1 (GSTM1) mRNA, protein and DNA methylation in mice, and the potential prevention of aspirin (ASP). This study firstly determined the BPDE-DNA adduct formation in an acute toxicity test of a large dose in mice induced by B[a]P, which subsequently detected CYP1A1, GSTP1, and GSTM1 at levels of mRNA, protein, and DNA methylation in the organs of mice in a subacute toxicity test at appropriate doses and the potential prevention of ASP, using the methods of real-time quantitative PCR (QPCR), western blotting, and real-time methylation-specific PCR (MSP), respectively. The results verified that B[a]P induced the formation of BPDE-DNA adduct in all the organs of mice in an acute toxicity test, and the order of concentration of which was lung > kidney > liver > brain. In a subacute toxicity test, following B[a]P treatment, mice showed a dose-dependent slowdown in body weight gain and abnormalities in behavioral and cognitive function and which were alleviated by ASP co-treatment. Compared to the controls, following B[a]P treatment, CYP1A1 was significantly induced in all organs in mice at mRNA level (P < 0.05), was suppressed in the lung and cerebrum of mice at protein level, and inhibited at DNA methylation level in the liver, lung, and cerebrum, whereas GSTP1 and GSTM1 at mRNA, protein, and DNA methylation levels showed organ-specific changes in mice following B[a]P treatment, which was generally alleviated by ASP intervention. In conclusion, B[a]P induced BPDE-DNA adduct formation in all organs in mice and altered the mRNA, protein, and DNA methylation levels in CYP1A1, GSTP1, and GSTM1 in an organ-dependent pattern, which could be related to the organ toxicity and mechanism of B[a]P. ASP intervention may be an effective measure to prevent B[a]P toxicity. The findings provide scientific evidence for further study on the organ toxicity and mechanisms of B[a]P. [ABSTRACT FROM AUTHOR]

Simple Summary: Antibiotics are medicines used to prevent and treat infections in humans, animals, and plants. Antibiotic resistance is a naturally occurring phenomenon that has emerged as one of the most significant threats to global health and food security. Bacteria have the ability to acquire mutations that render them resistant to antibiotic molecules, contributing to the spread of resistance. The misuse and overuse of antibiotics have played a pivotal role in driving the development and proliferation of antibiotic resistance. The United Nations is estimating that by 2050, up to 10 million human deaths each year will be caused by the "superbugs", very dangerous pathogens resistant to multiple antibiotic molecules. There will be health and macroeconomic consequences for the world if antimicrobial resistance is not tackled. The availability of antibiotics without prescription contributes to their overuse and misuse. Urgent measures are required to mitigate these issues and their substantial global impact. One of these measures is the search for new antibiotics designed on the basis of new targets of resistance. In this review, we show that enzymes called flavin monooxygenases could be a new and so-far-underseen candidate. Carbapenems are a group of broad-spectrum beta-lactam antibiotics that in many cases are the last effective defense against infections caused by multidrug-resistant bacteria, such as some strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Resistance to carbapenems has emerged and is beginning to spread, becoming an ongoing public-health problem of global dimensions, causing serious outbreaks, and dramatically limiting treatment options. This paper reviews the role of flavin monooxygenases in antibiotic resistance, with a specific focus on carbapenem resistance and the recently discovered mechanism mediated by Baeyer–Villiger monooxygenases. Flavin monooxygenases are enzymes involved in the metabolism and detoxification of compounds, including antibiotics. Understanding their role in antibiotic resistance is crucial. Carbapenems are powerful antibiotics used to treat severe infections caused by multidrug-resistant bacteria. However, the rise of carbapenem-resistant strains poses a significant challenge. This paper explores the mechanisms by which flavin monooxygenases confer resistance to carbapenems, examining molecular pathways and genetic factors. Additionally, this paper highlights the discovery of Baeyer–Villiger monooxygenases' involvement in antibiotic resistance. These enzymes catalyze the insertion of oxygen atoms into specific chemical bonds. Recent studies have revealed their unexpected role in promoting carbapenem resistance. Through a comprehensive analysis of the literature, this paper contributes to the understanding of the interplay between flavin monooxygenases, carbapenem resistance, and Baeyer–Villiger monooxygenases. By exploring these mechanisms, it aims to inform the development of strategies to combat antibiotic resistance, a critical global health concern. [ABSTRACT FROM AUTHOR]

This work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The formation of GSH S-conjugate of C-2028 in liver subfractions followed Michaelis-Menten kinetics. We found that C-2028 was conjugated with GSH preferentially by GSTM1-1, revealing a sigmoidal kinetic model. Using a colorimetric assay (MTT test), we initially assessed the cellular GST/GSH-dependent biotransformation of C-2028 in relation to cytotoxicity against Du-145 human prostate cancer cells in the presence or absence of the modulator of GSH biosynthesis. Pretreatment of cells with buthionine sulfoximine resulted in a cytotoxicity decrease, suggesting a possible GSH-mediated bioactivation process. Altogether, our results confirmed the importance of GSH conjugation in C-2028 metabolism, which humans must consider when planning a treatment strategy. Finally, nuclear magnetic resonance spectroscopy elucidated the structure of the GSH-derived product of C-2028. Hence, synthesizing the compound standard necessary for further advanced biological and bioanalytical investigations will be achievable. [ABSTRACT FROM AUTHOR]

The present study deals with a new highly effective functional product, a dietary supplement, to improve gut biocenosis and support metabolic detoxification. The supplement includes the following ingredients (mg per capsule): postbiotic metafiltrate -200; natural zeolite -130.36; polysorbovit - 105 (soluble dietary fiber - 100); silicon dioxide - 14.46; lipase - 10; bromelain - 10; papain - 10; cellulase - 10; rutin - 6; chitosan - 5; lysozyme hydrochloride - 5. The supplement is considered innovative as capsules have a special enteric coating to provide successive and targeted delivery of ingredients to the gastrointestinal tract cells while preserving safety and bioactivity. The antimicrobial and antifungal activity of the postbiotic metafiltrate has been studied. The mechanism of endotoxin neutralization and biocenosis normalization is characterized by the following factors: the destruction of toxic peptidoglycans of the bacterial cell wall and proteins and peptides with different chain lengths; elimination of Candida albicans cells by destroying bonds in the beta-glycan molecule of the fungal cell wall; cleavage of toxic lipid A of lipopolysaccharides; the influence of the culture fluid metabolites of probiotic microorganisms; high sorption capacity and selectivity for endotoxins, toxic metabolites, pathogenic microorganisms, free radicals, allergens, and antigens. The product has been included in the volunteers' diet and its efficacy has been assessed. The product's role in metabolic detoxification and biocenosis normalization has been studied. The recommended dosage is 1 capsule twice a day with a meal for 30 days. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heavy selection pressure prompted the development of resistance in a serious cotton pest tarnished plant bug (TPB), Lygus Lineolaris in the mid‐southern United States. Conversely, a laboratory resistant TPB strain lost its resistance to five pyrethroids and two neonicotinoids after 36 generations without exposure to any insecticide. It is worthwhile to examine why the resistance diminished in this population and determine whether the resistance fade away has practical value for insecticide resistance management in TPB populations. RESULTS: A field‐collected resistant TPB population in July (Field‐R1) exhibited 3.90–14.37‐fold resistance to five pyrethroids and two neonicotinoids, while another field‐collected TPB population in April (Field‐R2) showed much lower levels of resistance (0.84–3.78‐fold) due to the absence of selection pressure. Interestingly, after 36 generations without exposure to insecticide, the resistance levels in the same population [laboratory resistant strain (Lab‐R)] significantly decreased to 0.80–2.09‐fold. The use of detoxification enzyme inhibitors had synergistic effects on permethrin, bifenthrin and imidacloprid in resistant populations of Lygus lineolaris. The synergism was more pronounced in Field‐R2 than laboratory susceptible (Lab‐S) and Lab‐R TPB population. Moreover, esterase, glutathione S‐transferase (GST), and cytochrome P450‐monooxygenases (P450) enzyme activities increased significantly by approximately 1.92‐, 1.43‐, and 1.44‐fold in Field‐R1, respectively, and 1.38‐fold increased P450 enzyme activities in Field‐R2 TPB population, compared to the Lab‐S TPB. In contrast, the three enzyme activities in the Lab‐R strain were not significantly elevated anymore relative to the Lab‐S population. Additionally, Field‐R1 TPB showed elevated expression levels of certain esterase, GST and P450 genes, respectively, while Field‐R2 TPB overexpressed only P450 genes. The elevation of these gene expression levels in Lab‐R expectedly diminished to levels close to those of the Lab‐S TPB populations. CONCLUSION: Our results indicated that the major mechanism of resistance in TPB populations was metabolic detoxification, and the resistance development was likely conferred by increased gene expressions of esterase, GST, and P450 genes, the fadeaway of the resistance may be caused by reversing the overexpression of esterase, GST and P450. Without pesticide selection, resistant gene (esterase, GST, P450s) frequencies declined, and detoxification enzyme activities returned to Lab‐S level, which resulted in the recovery of the susceptibility in the resistant TPB populations. Therefore, pest's self‐purging of insecticide resistance becomes strategically desirable for managing resistance in pest populations. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

As a whole food, the potential health benefits of table grapes have been widely studied. Some individual constituents have garnered great attention, particularly resveratrol, but normal quantities in the diet are meniscal. On the other hand, the grape contains hundreds of compounds, many of which have antioxidant potential. Nonetheless, the achievement of serum or tissue concentrations of grape antioxidants sufficient to mediate a direct quenching effect is not likely, which supports the idea of biological responses being mediated by an indirect catalytic-type response. We demonstrate herein with Hsd:ICR (CD-1® Outbred, 18–24 g, 3–4 weeks old, female) mice that supplementation of a semi-synthetic diet with a grape surrogate, equivalent to the human consumption of 2.5 servings per day for 12 months, modulates gene expression in the liver, kidney, colon, and ovary. As might be expected when sampling changes in a pool of over 35,000 genes, there are numerous functional implications. Analysis of some specific differentially expressed genes suggests the potential of grape consumption to bolster metabolic detoxification and regulation of reactive oxygen species in the liver, cellular metabolism, and anti-inflammatory activity in the ovary and kidney. In the colon, the data suggest anti-inflammatory activity, suppression of mitochondrial dysfunction, and maintaining homeostasis. Pathway analysis reveals a combination of up- and down-regulation in the target tissues, primarily up-regulated in the kidney and down-regulated in the ovary. More broadly, based on these data, it seems logical to conclude that grape consumption leads to modulation of gene expression throughout the body, the consequence of which may help to explain the broad array of activities demonstrated in diverse tissues such as the brain, heart, eye, bladder, and colon. In addition, this work further supports the profound impact of nutrigenomics on mammalian phenotypic expression. [ABSTRACT FROM AUTHOR]

Plants with innate disease and pest resistance can contribute to more sustainable agriculture. Natural defence compounds produced by plants have the potential to provide a general protective effect against pathogens and pests, but they are not a primary target in resistance breeding. Here, we identified a wild relative of potato, Solanum commersonii, that provides us with unique insight in the role of glycoalkaloids in plant immunity. We cloned two atypical resistance genes that provide resistance to Alternaria solani and Colorado potato beetle through the production of tetraose steroidal glycoalkaloids (SGA). Moreover, we provide in vitro evidence to show that these compounds have potential against a range of different (potato pathogenic) fungi. This research links structural variation in SGAs to resistance against potato diseases and pests. Further research on the biosynthesis of plant defence compounds in different tissues, their toxicity, and the mechanisms for detoxification, can aid the effective use of such compounds to improve sustainability of our food production. [ABSTRACT FROM AUTHOR]

The long-distance migration of polycyclic aromatic hydrocarbons (PAHs) promotes their release into the marine environment, posing a serious threat to marine life. Studies have shown that PAHs have significant immunotoxicity effects on bivalves, but the exact mechanism of immunotoxicity remains unclear. This paper aims to investigate the effects of exposure to 0.4, 2, and 10 μg/L of benzo(a)pyrene (B[a]P) on the immunity of Chlamys farreri under environmental conditions, as well as the potential molecular mechanism. Multiple biomarkers, including phagocytosis rate, metabolites, neurotoxicity, oxidative stress, DNA damage, and apoptosis, were adopted to assess these effects. After exposure to 0.4, 2, and 10 μg/L B[a]P, obvious concentration-dependent immunotoxicity was observed, indicated by a decrease in the hemocyte index (total hemocyte count, phagocytosis rate, antibacterial and bacteriolytic activity). Analysis of the detoxification metabolic system in C. farreri revealed that B[a]P produced B[a]P-7,8-diol-9,10-epoxide (BPDE) through metabolism, which led to an increase in the expression of protein tyrosine kinase (PTK). In addition, the increased content of neurotransmitters (including acetylcholine, γ -aminobutyric acid, enkephalin, norepinephrine, dopamine, and serotonin) and related receptors implied that B[a]P might affect immunity through neuroendocrine system. The changes in signal pathway factors involved in immune regulation indicated that B[a]P interfered with Ca2+ and cAMP signal transduction via the BPDE-PTK pathway or neuroendocrine pathway, resulting in immunosuppression. Additionally, B[a]P induced the increase in reactive oxygen species (ROS) content and DNA damage, as well as an upregulation of key genes in the mitochondrial pathway and death receptor pathway, leading to the increase of apoptosis rate. Taken together, this study comprehensively investigated the detoxification metabolic system, neuroendocrine system, and cell apoptosis to explore the toxic mechanism of bivalves under B[a]P stress. [ABSTRACT FROM AUTHOR]

Background: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine. Hypothesis: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers. Methods: We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP. Results: (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends. Conclusion: ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant. [ABSTRACT FROM AUTHOR]

Background. In this study, the effects of pomegranate-black carrot juice mixture on serum and erythrocytes of sedentary individuals who had exhaustion test were investigated. Methods. A total of 20 men voluntarily participated in the study. Blood samples were obtained from participants on three conditions. First, before the study, blood samples of participants were collected (baseline). Second, the same participants performed in the 20-meter shuttle run test for 1 week each day and were subjected to oxidative stress. Lastly, the same participants were given a mixture of pomegranate-black carrot juices (100 ml/100 ml) for a week, 45 minutes prior to the 20-meter shuttle run test, and the stress + supplement was performed. Blood samples were taken at the end of each process. Results. In the erythrocytes, while the oxidative stress condition malondialdehyde (MDA) level and carbonic anhydrase (CA) enzyme activity levels increased compared to the baseline, reduced glutathione (GSH) level, glutathione reductase (GR), and glutathione S-transferase (GST) enzyme activity levels decreased. In stress + supplement conditions, while GSH and GR levels increased according to oxidative stress conditions, CA and MDA levels decreased. While the lactate dehydrogenase (LDH) level of the oxidative stress condition increased compared to the baseline, the LDH level of the stress + supplement decreased compared to the oxidative stress condition. Conclusions. Our results showed that the level of oxidative stress in subjects exposed to the exhaustion test decreased with the mixture of pomegranate-black carrot juices. [ABSTRACT FROM AUTHOR]

Understanding the mechanism of detoxification initiation in arthropods after pesticide exposure is crucial. Although the identity of transcription factors that induce and regulate the expression of detoxification genes in response to pesticides is beginning to emerge, whether transcription factors directly interact with xenobiotics is unclear. The findings of this study revealed that a nuclear hormone receptor, Tetranychus cinnabarinus hormone receptor (HR) TcHR96h, regulates the overexpression of the detoxification gene TcGSTm02, which is involved in cyflumetofen resistance. The nuclear translocation of TcHR96h increased after cyflumetofen exposure, suggesting direct binding with cyflumetofen. The direct binding of TcHR96h and cyflumetofen was supported by several independent proteomic assays that quantify interactions with small molecules. Together, this study proposes a model for the initiation of xenobiotic detoxification in a polyphagous agricultural pest. These insights not only provide a better understanding of the mechanisms of xenobiotic detoxification and metabolism in arthropods, but also are crucial in understanding adaptation in polyphagous herbivores. Author summary: Phytophagous arthropods possess a powerful system of detoxification that involves several major metabolic detoxification gene families. What is currently clear is how detoxification enzymes interact with chemical molecules. However, it remains elusive how insects sense the xenochemicals and signal to activate the downstream detoxification system when faced with pesticide exposure. The present study identified a xenobiotic sensor that initiates a detoxification system and a novel pathway in the detoxification of cyflumetofen in a representative mite species. The information will contribute a deeper insight into the whole process of arthropods even animal detoxification and metabolism. [ABSTRACT FROM AUTHOR]

Background: Environmental changes are expected to intensify in the future. The invasion of toxic plants under environmental changes may change herbivore feeding environments. Herbivores living long-term in toxic plant-feeding environments will inevitably ingest plant secondary metabolites (PSMs), and under different feeding environments are likely to have unique protection mechanisms that support improved adaptation to PSMs in their habitat. We aimed to compare different subterranean herbivore population responses and adaptations to toxic plants to unveil their feeding challenges. Results: Here, we investigated the adaptive capacity of the liver in two geographically separated populations of plateau zokors (Eospalax baileyi) before and after exposure to the toxic plant Stellera chamaejasme (SC), at the organ, biochemical, and transcriptomic levels. The results showed no significant liver granules or inflammatory reactions in the Tianzhu (TZ) population after the SC treatment. The transaminase level in the TZ population was significantly lower than that in the Luqu population. Transcriptome analysis revealed that the TZ population exhibited interactions with other detoxification metabolic pathways by oxytocin pathway-associated genes, including diacylglycerol lipase alpha (Dagla), calcium/calmodulin dependent protein kinase II Alpha (Camk2a), and CD38 molecule (Cd38). The phase II process of liver drug metabolism increased to promote the rate of metabolism. We found that alternative splicing (AS) and the expression of the cyclin D (Ccnd1) gene interact—a TZ population hallmark—reduced liver inflammatory responses. Conclusion: Our study supports the detoxification limitation hypothesis that differences in liver detoxification metabolism gene expression and AS are potential factors in herbivore adaptation to PSMs and may be a strategy of different herbivore populations to improve toxic plant adaptability. [ABSTRACT FROM AUTHOR]

Cytochrome P450 monooxygenase (CYP) is one of the three detoxification metabolic enzymes in insects, and is involved in the metabolism and transformation of endogenous substances as well as the activation and degradation of exogenous compounds. This study aims to reveal the molecular mechanism of CYP9E2 in Tribolium castaneum in adapting to high-CO2 stress. By predicting the sequence function of CYP9E2, analyzing the temporal and spatial expression profile of TcCYP9E2, and using RNAi to silence TcCYP9E2 combined with a high-CO2 stress treatment, we measured the carbohydrate content, trehalase activity, and gene expression levels in trehalose metabolism of T. castaneum. A bioinformatics analysis showed that the predicted molecular weight of the protein encoded by TcCYP9E2 is 60.15, the theoretical isoelectric point is 8.63, there is no signal peptide, and the protein is hydrophilic. An evolutionary tree analysis showed that TcCYP9E2 belongs to the CYP6 family and belongs to the CYP3 group; and the spatiotemporal expression profile results showed that TcCYP9E2 was highly expressed in the larvae midgut 48 h after injection of dsCYP9E2, with survival rates decreasing with the increase in CO2 concentration. Under the condition of 75% CO2, the contents of glycogen, glucose, ATP, and membrane-bound trehalase decreased significantly after the injection of dsCYP9E2. The expression of TRE-1, TRE-2, and GP in trehalose metabolism and energy pathways was significantly downregulated. [ABSTRACT FROM AUTHOR]

Exposure of Eriopis connexa (Germar) to pyrethroid residues in agroecosystems has resulted in selection for resistance (R). Pyrethroid resistance allows E. connexa to survive lambda‐cyhalothrin applications. Following a field release of E. connexa, development of resistance in an incipient population may depend on three major factors such as the maintenance of: (i) selection pressure, (ii) frequency of mating with susceptible phenotypes (S) and (iii) differential reproductive performance due to the fitness costs associated with resistance. To investigate the potential effects of these three factors on the development of pyrethroid resistance by progeny of field released E. connexa, our experiments included panmictic mating between R and S phenotypes, followed by descendant rearing with and without insecticide selection pressure, reselection and determination of resistance levels. In addition, we measured the reproductive performance of the parental R and S phenotypes and their descendants to assess the cost of resistance after crossing and reselection. Survival of R × S descendants exposed to lambda‐cyhalothrin was reduced across successive generations in the absence of selection pressure, but still enhanced after four generations indicating the persistent presence of resistant phenotypes in the population. Under selection pressure with exposure to lambda‐cyhalothrin applied at label rates, descendant survival was >50%. Fecundity and survival were higher in the first‐generation of crossed R × S females, but higher fecundity was not sustained after reselection. Adults of the R population exhibited a fitness cost, reduced longevity, when compared to S phenotypes and R × S crossed populations. Therefore, resistance maintenance in E. connexa after release will depend on selection pressures imposed by insecticide exposure. In the absence of selection pressure, the phenotype for resistance was reduced, but not completely lost. Further, resistant phenotypes can be reselected following insecticide exposure and this can explain, in part, the high frequency of field‐evolved resistance to lambda‐cyhalothrin in E. connexa. [ABSTRACT FROM AUTHOR]

Tendinopathies are common disabling conditions in equine and human athletes. The etiology is still unclear, although reactive oxygen species (ROS) and oxidative stress (OS) seem to play a crucial role. In addition, OS has been implicated in the failure of tendon lesion repair. Platelet-rich plasma (PRP) is rich in growth factors that promote tissue regeneration. This is a promising therapeutic approach in tendon injury. Moreover, growing evidence has been attributed to PRP antioxidant effects that can sustain tissue healing. In this study, the potential antioxidant effects of PRP in tenocytes exposed to oxidative stress were investigated. The results demonstrated that PRP reduces protein and lipid oxidative damage and protects tenocytes from OS-induced cell death. The results also showed that PRP was able to increase nuclear levels of redox-dependent transcription factor Nrf2 and to induce some antioxidant/phase II detoxifying enzymes (superoxide dismutase 2, catalase, heme oxygenase 1, NAD(P)H oxidoreductase quinone-1, glutamate cysteine ligase catalytic subunit and glutathione, S-transferase). Moreover, PRP also increased the enzymatic activity of catalase and glutathione S-transferase. In conclusion, this study suggests that PRP could activate various cellular signaling pathways, including the Nrf2 pathway, for the restoration of tenocyte homeostasis and to promote tendon regeneration and repair following tendon injuries. [ABSTRACT FROM AUTHOR]

Coumarin and its derivatives are plant-derived compounds that exhibit potent insecticidal properties. In this study, we found that natural coumarin significantly inhibited the growth and development of Spodoptera litura larvae through toxicological assay. By transcriptomic sequencing, 80 and 45 differentially expressed genes (DEGs) related to detoxification were identified from 0 to 24 h and 24 to 48 h in S. litura after coumarin treatment, respectively. Enzyme activity analysis showed that CYP450 and acetylcholinesterase (AChE) activities significantly decreased at 48 h after coumarin treatment, while glutathione S-transferases (GST) activity increased at 24 h. Silencing of SlCYP324A16 gene by RNA interference significantly increased S. litura larval mortality and decreased individual weight after treatment with coumarin. Additionally, the expression levels of DEGs involved in glycolysis and tricarboxylic acid (TCA) cycle were inhibited at 24 h after coumarin treatment, while their expression levels were upregulated at 48 h. Furthermore, metabonomics analysis identified 391 differential metabolites involved in purine metabolism, amino acid metabolism, and TCA cycle from 0 to 24 h after treated with coumarin and 352 differential metabolites associated with ATP-binding cassette (ABC) transporters and amino acid metabolism. These results provide an in-depth understanding of the toxicological mechanism of coumarin on S. litura. [ABSTRACT FROM AUTHOR]

Background: Anopheles stephensi is the main vector of malaria in Iran. This study aimed to determine the susceptibility of An. stephensi from the south of Iran to bendiocarb and to investigate biochemical and molecular resistance mechanisms in this species. Methods: Wild An. stephensi were collected from Hormozgan Province and reared to the adult stage. The susceptibility test was conducted according to the WHO protocols using bendiocarb impregnated papers supplied by WHO. Also, field An. Stephensi specimens were collected from south of Kerman and Sistan and Baluchistan Provinces. To determine the G119S mutation in the acetylcholinesterase (Ace1) gene, PCR-RFLP using AluI restriction enzyme and PCR direct-sequencing were performed for the three field populations and compared with the available GenBank data. Also, biochemical assays were performed to measure alpha and beta esterases, insensitive acetylcholinesterase, and oxidases in the strains. Results: The bioassay tests showed that the An. stephensi field strain was resistant to bendiocarb (mortality rate 89%). Ace1 gene analysis revealed no G119S in the three field populations. Blast search of sequences revealed 98–99% identity with the Ace1 gene from Pakistan and India respectively. Also, the results of biochemical tests revealed the high activity of non-sensitive acetylcholinesterase, alpha and beta-esterase in the resistant strain compared to the susceptible strain. No G119S was detected in this study additionally the enhanced enzyme activity of esterases and acetylcholinesterase suggesting that resistance was metabolic. Conclusion: The use of alternative malaria control methods and the implementation of resistance management strategies are suggested in the study area. [ABSTRACT FROM AUTHOR]

The cotton whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is one of the important pests of agricultural products that causes great economic losses. In this research, the effect of spirotetramat on three different developmental stages of the pest was studied in several populations that were collected from different provinces of Iran. Bioassay was done by leaf disk method. The results showed a higher sensitivity of the 2nd nymph stage compared to the adult stage and the egg stage; while the adult stage showed the least sensitivity to spirotetramat. The highest rate of resistance in different developmental stages was observed in the Jiroft population The LC50 ratios of adults in Karaj, Yazd, Pishwa, and Jiroft populations to sensitive one (Marand) were 7.6, 6.2, 4.2, and 9.6, respectively. For second instar nymphs, the ratios were 2.0, 2.2, 2.1, and 5.5 respectively. The investigation on detoxification enzymes indicated the higher activity of monooxygenase enzyme in the resistant population of Jiroft (3.34-fold) compared to the Marand population, which indicates the effective role of these enzymes in creating resistance. According to the results, to prevent resistance development, it is necessary to use other chemical compounds with different modes of action to prevent the occurrence of cross-resistance while affecting different developmental stages of pests. [ABSTRACT FROM AUTHOR]

The treatment of heavy metals in sewage treatment systems has gained more attention with the increase in heavy metal hazards. Tubificidae in sludge reduction have been widely studied; however, little is known about the effect of Tubificidae in the treatment of Cr-containing wastewater. In this study, the mechanism of Tubificidae in the sludge reduction system with Cr stress was studied. Predation experiments by Tubificidae in a Cr-containing sludge reduction system were conducted to investigate the changes in enzyme activities in the Tubificidae under different concentrations of Cr, and the distribution of Cr in the sludge reduction reactor was analyzed. The kinetic model of uptake and elimination of Cr in Tubificidae was established. The results showed that the maximum activation multiplier factor of superoxide dismutase (SOD) activity was 1.95 under the low concentration of Cr(VI), which indicated that Tubificidae had a certain detoxification. After the effect of Tubificidae on Cr(VI) experiments, the Cr concentrations in Tubificidae, sludge, and feces increased first and then decreased with exposure time, and the proportion of total Cr and Cr(VI) in the sludge decreased from 71.98% and 42.7% to 29.18% and 6.82%, respectively. The detoxification mechanism of the Tubificidae could be activated with Cr stress, and 63.22% of the Cr(VI) was converted to Cr(III). The bioconcentration factor (BCF) for theoretical equilibrium was 446, the maximum bioaccumulation factor (BAF) reached 0.97 on the 15th day. It can be seen that Tubificidae could be considered a good scavenger of environmental Cr(VI). The hyperbolic model fits the process of Cr uptake and elimination well and can be used as a predictive tool for Tubificidae accumulation. [ABSTRACT FROM AUTHOR]

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and a theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 0.050 µM−4·s−1 and 0.055 s−1, respectively, for the dimer–decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer–decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer–decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation state to hydrogen peroxide insult. By accounting for the dimer–decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models. [ABSTRACT FROM AUTHOR]

Turbot aquaculture production is an important economic activity in several countries around the world; nonetheless, the incidence of diseases, such furunculosis, caused by the etiological agent A. salmonicida subsp. salmonicida, is responsible for important losses to this industry worldwide. Given this perspective, this study aimed to evaluate early immune responses in turbot (S. maximus L.) following infection with A. salmonicida subsp. salmonicida. For this, 72 fish were individually weighed and randomly distributed into 6 tanks in a circulating seawater system. For the bacterial challenge, half of the individuals (3 tanks with 36 individuals) were infected using a peritoneal injection with the bacterial suspension, while the other half of individuals were injected with PBS and kept as a control group. Several factors linked to the innate immune response were studied, including not only haematological (white blood cells, red blood cells, haematocrit, haemoglobin, mean corpuscular volume, mean cell haemoglobin, mean corpuscular haemoglobin concentration, neutrophils, monocytes, lymphocytes, thrombocytes) and oxidative stress parameters, but also the analyses of the expression of 13 key immune-related genes (tnf-α, il-1β, il-8, pparα-1, acox1, tgf-β1, nf-kB p65, srebp-1, il-10, c3, cpt1a, pcna, il-22). No significant differences were recorded in blood or innate humoral parameters (lysozyme, anti-protease, peroxidase) at the selected sampling points. There was neither any evidence of significant changes in the activity levels of the oxidative stress indicators (catalase, glutathione S-transferase, lipid peroxidation, superoxide dismutase). In contrast, pro-inflammatory (tnf-α, il-1β), anti-inflammatory (il-10), and innate immune-related genes (c3) were up-regulated, while another gene linked with the lipid metabolism (acox1) was down-regulated. The results showed new insights about early responses of turbot following infection with A. salmonicida subsp. salmonicida. [ABSTRACT FROM AUTHOR]

Insects have a limited host range due to genomic adaptation. Thysanoptera, commonly known as thrips, occupies distinct feeding habitats, but there is a lack of comparative genomic analyses and limited genomic resources available. In this study, the chromosome-level genome of Stenchaetothrips biformis, an oligophagous pest of rice, is assembled using multiple sequencing technologies, including PacBio, Illumina short-reads, and Hi-C technology. A 338.86 Mb genome is obtained, consisting of 1269 contigs with a contig N50 size of 381 kb and a scaffold N50 size of 18.21 Mb. Thereafter, 17,167 protein-coding genes and 36.25% repetitive elements are annotated. Comparative genomic analyses with two other polyphagous thrips, revealing contracted chemosensory-related and expanded stress response and detoxification gene families in S. biformis, potentially facilitating rice adaptation. In the polyphagous thrips species Frankliniella occidentalis and Thrips palmi, expanded gene families are enriched in metabolism of aromatic and anthocyanin-containing compounds, immunity against viruses, and detoxification enzymes. These expansion gene families play crucial roles not only in adapting to hosts but also in development of pesticide resistance, as evidenced by transcriptome results after insecticides treatment. This study provides a chromosome-level genome assembly and lays the foundation for further studies on thrips evolution and pest management. A chromosome-level genome assembly of the rice crop pest, Stenchaetothrips biformis, and comparative genomic analysis to two other thrip species highlights adaptive differences among these thrips and may inform future pest control strategies. [ABSTRACT FROM AUTHOR]

1. The influence of cyanobacteria on interspecies interactions has received growing attention as a predictor of aquatic ecosystem function. It is well‐known that cyanobacteria greatly affect predator‐induced phenotypic plasticity in planktonic animals. However, the underlying molecular mechanism remains unclear. 2. Here, we used Daphnia pulex as a model organism for inducible defence, examining its morphological and life‐history responses to fish kairomone while feeding on 100% Chlorella pyrenoides, or while feeding on 70% Chlorella and either microcystin‐producing or ‐free Microcystis aeruginosa, separately. Transcriptome profiles of kairomone‐exposed D. pulex fed different types of food were detected using RNA‐seq. How the differentially expressed genes and pathways identified are responsible for the altered adaptive traits under Microcystis stress was discussed. 3. Daphnia pulex fed 100% Chlorella matured at a smaller body size, elongated tail spine length, and produced smaller offspring as adaptive morphological and reproductive responses to fish kairomone. These anti‐predation defences entailed a cost in decreased somatic growth rate. Microcystis stress caused defence trade‐offs in both morphology and reproduction: reduction of body size at maturity was stronger whereas tail spine elongation was unchanged or inhibited. Given that reproductive investment was reduced overall in Daphnia exposed to fish kairomones, there was a trade‐off for unchanged offspring size by reducing offspring number in Daphnia fed Microcystis. Defence‐induced costs to growth were increased by Microcystis exposure. 4. Transcriptome analysis revealed that neuronal signals including acetylcholine and glutamate signalling implicated in kairomone reception and/or transmission exhibited stronger responses under Microcystis stress. Cuticle development associated with the biosynthesis of wax esters and chitin, modification of lipo‐chitin saccharides, and the stability of collagen triple helix apparently participated in the morphological changes. The arachidonic acid pathway and biosynthesis of cholesterol and steroid hormones mediated altered reproductive performance. In addition, metabolic processes such as detoxification, food assimilation, lysosome dysfunction and apoptosis activation were involved in the survival and growth of Daphnia, which may contribute to the increased defence‐induced cost in growth when fed Microcystis. 5. Taken together, these findings advance our understanding of the molecular mechanisms underlying anti‐predation defensive responses by Daphnia to cyanobacterial stress. This work also provides a reference for further exploring the functional genes that mediate zooplankton–fish coevolution dynamics under eutrophic conditions. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition that results from an overwhelming and disproportionate host response to an infection. Currently, the quality and extent of the immune response are evaluated based on clinical symptoms and the concentration of inflammatory biomarkers released or expressed by the immune cells. However, the host response toward sepsis is heterogeneous, and the roles of the individual immune cell types have not been fully conceptualized. During sepsis, the spleen plays a vital role in pathogen clearance, such as bacteria by an antibody response, macrophage bactericidal capacity, and bacterial endotoxin detoxification. This study uses Raman spectroscopy to understand the splenic T-lymphocyte compartment profile changes during bona fide bacterial sepsis versus hyperinflammatory endotoxemia. The Raman spectral analysis showed marked changes in splenocytes of mice subjected to septic peritonitis principally in the DNA region, with minor changes in the amino acids and lipoprotein areas, indicating significant transcriptomic activity during sepsis. Furthermore, splenocytes from mice exposed to endotoxic shock by injection of a high dose of lipopolysaccharide showed significant changes in the protein and lipid profiles, albeit with interindividual variations in inflammation severity. In summary, this study provided experimental evidence for the applicability and informative value of Raman spectroscopy for profiling the immune response in a complex, systemic infection scenario. Importantly, changes within the acute phase of inflammation onset (24 h) were reliably detected, lending support to the concept of early treatment and severity control by extracorporeal Raman profiling of immunocyte signatures. [ABSTRACT FROM AUTHOR]