Prevalence of T-2 Toxin in the Food and Beverages of Residents Living in a Kashin-Beck-Disease Area of Qamdo, Tibet.

It has been strongly suggested that selenium deficiency and T-2 toxin contamination have a strong relationship with the occurrence and development of Kashin-Beck disease (KBD). In order to provide information for understanding the high prevalence of KBD in Tibet, this study collected the responses to a cubital venous blood and dietary questionnaire of 125 subjects including 75 KBD patients and 50 healthy controls in a KBD-prevalent county (Luolong County) in Tibet, China. A total of 10 household local families were randomly selected in this area, and local diet samples of brick tea, Zanba powder, milk residue, and hulless Barley were collected from these residents. Selenium content in blood was detected by inductively coupled plasma mass spectrometry (ICP-MS). The T-2 toxin contamination level in food sample was assayed using an ELISA kit. The selenium levels of patients and controls were 42.0 ± 19.8 and 56.06 ± 22.4 µg/L, respectively. The serum selenium level in controls was higher than that in patients, but there was no significant difference, and the serum selenium level both in patients and controls in Tibet was lower than the normal range. The results of the dietary survey showed that the number of respondents who consumed butter tea was large; 46.67% of patients indicated that they drank buttered tea every day, which was significantly higher than in controls. The contents of T-2 toxin in Zanba powder, milk residue, hulless barley and drinking water samples were below the detection limit (0.05 µg/kg); this result was labeled Tr. Unexpectedly, the contents of T-2 toxin in brick tea were higher, with average levels of 424 ± 56 µg/kg in Detong village and 396 ± 24 µg/kg in Langcuo village. For the first time, we report the presence of an extremely high concentration of T-2 toxin in brick tea of Tibet.

Mechanism of Apoptosis in Porcine Ovarian Granulosa Cells Triggered by T-2 Toxin.

T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its toxicity remain unclear. With the goal of learning how T-2 affects reproduction in animals, we utilized primary porcine ovarian granulosa cells (pGCs) as a carrier in vitro and constructed concentration models for analyzing cell morphology and RNA-sequencing (RNA-seq). Our findings showed that T-2 could influence pGCs morphology, induce cell cycle arrest, and promote apoptosis in a dose-dependent manner. The results of RNA-seq analyses indicated that a total of 8216 genes exhibited significant differential expression (DEG) following T-2 treatment, of which 4812 were observed to be down-regulated and 3404 were up-regulated. The DEGs following T-2 toxin treatment of pGCs had a notable impact on many metabolic pathways such as PI3K-Akt, Ras, MAPK, and apoptosis, which in turn altered important physiological processes. Gene set enrichment analysis (GSEA) indicated that the differences in the harmful effects of T-2 might be caused by the varying control of cellular processes and the pathway responsible for steroid metabolism. These results present further insights regarding the mechanism of T-2 action on sow reproductive toxicity, enhance our understanding of T-2 reproductive toxicological effects, and lay a theoretical foundation for the judicious prevention of T-2-induced reproductive toxicity.

Impact of Environmental Conditions on the Concentrations of Trichothecenes, Their Glucosides, and Emerging Fusarium Toxins in Naturally Contaminated, Irradiated, and Fusarium langsethiae Inoculated Oats.

Trichothecenes produced by Fusarium species are commonly detected in oats. However, the ratios of the concentrations of free trichothecenes and their conjugates and how they are impacted by different interacting environmental conditions are not well documented. This study aims to examine the effect of water activity (0.95 and 0.98 aw) and temperature (20 and 25 °C) stress on the production of T-2 and HT-2 toxins, deoxynivalenol and their conjugates, as well as diacetoxyscirpenol (DAS). Multiple mycotoxins were detected using liquid chromatography-tandem mass spectrometry from 64 contaminated oat samples. The highest concentrations of HT-2-glucoside (HT-2-Glc) were observed at 0.98 aw and 20 °C, and were higher than other type A trichothecenes in the natural oats' treatments. However, no statistical differences were found between the mean concentrations of HT-2-Glc and HT-2 toxins in all storage conditions analysed. DAS concentrations were generally low and highest at 0.95 aw and 20 °C, while deoxynivalenol-3-glucoside levels were highest at 0.98 aw and 20 °C in the naturally contaminated oats. Emerging mycotoxins such as beauvericin, moniliformin, and enniatins mostly increased with a rise in water activity and temperature in the naturally contaminated oats treatment. This study reinforces the importance of storage aw and temperature conditions in the high risk of free and modified toxin contamination of small cereal grains.

Individual cytotoxicity of three major type A trichothecene, T-2, HT-2, and diacetoxyscirpenol in human Jurkat T cells.

Mycotoxins are toxic, fungal secondary metabolites that contaminate agricultural commodities, food, and feed. Among them, T-2, HT-2, and diacetoxyscirpenol (DAS; the major type A trichothecene) are primarily produced from Fusarium species. These mycotoxins exert numerous toxicological effects in animals and humans, such as dermatotoxicity, haematotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and immunotoxicity. In the present study, human Jurkat T cells were used as a model to investigate apoptotic cell death induced by T-2, HT-2, and DAS. The results showed that T-2, HT-2, and DAS decreased cell viability and increased production of Reactive Oxygen Species in a time- and dose-dependency. Based on their IC50 values, they could be ranked in decreasing order of cytotoxicity as T-2 > HT-2 > DAS. All tested mycotoxins caused DNA fragmentation, up-regulated cytochrome C, caspase 3, and caspase 9 mRNA levels, and down-regulated the relative expression of Bcl-2 and caspase 8. The effects of these trichothecenes on apoptosis were determined based on flow cytometry. At the IC50 concentrations, the percentages of apoptotic cells were significantly higher than for the controls. Taken together, these data suggested that T-2, HT-2, and DAS could induce apoptosis through the mitochondrial apoptotic pathway.

T-2 toxin-induced damage to articular cartilage in rats coincided with impaired autophagy linked to the HIF-1α/AMPK signaling axis.

T-2 toxin is one of the most toxic mycotoxins. People are primarily exposed to T-2 toxin through the consumption of spoiled food, typically over extended periods and at low doses. T-2 toxin can cause damage to articular cartilage. However, the exact mechanism is not fully understood. In this experiment, 36 male rats were divided into a control group, a solvent control group, and a T-2 toxin group. The rats in the T-2 toxin group were orally administered the toxin at a dosage of 100 ng/g BW/Day. The damage to articular cartilage and key proteins associated with the autophagy process and the HIF-1α/AMPK signaling axis was assessed at 4, 8, 12, and 16 weeks. Our findings indicate that T-2 toxin-induced damage to articular cartilage in rats coincided with impaired autophagy linked to the HIF-1α/AMPK signaling pathway. This study offers novel insights into the precise mechanism underlying T-2 toxin-induced damage to articular cartilage.

Modulatory interactions of T-2 and deoxynivalenol mycotoxins on murine femoral development and osteological integrity.

In this study, we conducted a systematic assessment of the effectsof deoxynivalenol (DON) and T-2 mycotoxins (T-2) on the developmental processes and structural integrity of murine femurs, considering both the isolated and synergistic effects of these toxins. To this end, we divided 72 male mice into nine groups, each subjected to varying dosages of T-2, DON, or their combinations. Over a four-week experimental period, meticulous monitoring was undertaken regarding the mice's body weight, biochemical markers of bone formation and resorption, and the activity of relevant cells. To comprehensively evaluate alterations in bone structure, we employed biomechanical analysis, micro-computed tomography (micro-CT), and transmission electron microscopy.Our findings unveiled a significant revelation: the mice exhibited a dose-dependent decrease in body weight upon exposure to individual mycotoxins, while the combined use of these toxins manifested an atypical antagonistic effect. Furthermore, we observed variations in the levels of calcium, phosphorus, and vitamin D, as well as adjustments in the activities of osteoblasts and osteoclasts, all intricately linked to the dosage and ratio of the toxins. Alterations in biomechanical properties were also noted to correlate with the dosage and combination of toxins. Analyses via micro-CT and transmission electron microscopy further corroborated the substantial impact of toxin dosage and combinations on both cortical and trabecular bone structures.In summation, our research unequivocally demonstrates the dose- and ratio-dependent detrimental effects of DON and T-2 mycotoxins on the growth and structural integrity of murine femurs. These insights accentuate the importance of a profound understanding of the potential risks these toxins pose to bone health, offering pivotal guidance for future toxicological research and public health preventative strategies.

Occurrence of mycotoxins in meat alternatives: Dietary exposure, potential health risks, and burden of disease.

This study aimed to present the occurrence of sixteen mycotoxins in 105 meat alternatives based on wheat, legumes, and vegetables from Italy. The targeted mycotoxins were aflatoxins (AFB1, AFB2, AFG1, AFG2), fumonisins B1 and B2 (FB1, FB2), alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), ochratoxin A (OTA), zearalenone (ZEN), T-2/HT-2 toxin, deoxynivalenol (DON), enniatin B (ENNB), and beauvericin (BEA). The occurrence of mycotoxins was between 0% (AFB2) - 97.4% (ENNB). Mycotoxin co-occurrence varied from binary combinations up to mixtures of twelve. To assess the dietary exposure and potential health risks we simulated the replacement of meat consumption for Italian consumers with meat alternatives. The cumulative exposure to Alternaria mycotoxins and trichothecenes indicated a potential health risk while the exposure to aflatoxins and ochratoxin A indicated a potential health concern related to liver and renal cancer in the model scenario. Moreover, we estimated the risk of liver cancer from exposure to AFB1 and quantified the potential burden using Disability-Adjusted Life Years (DALYs). Luckily, the potential risk of liver cancer was low between 0 and 0.05/100,000 individuals with an associated burden of disease of 0.83 DALYs/100,000 individuals. Taking into consideration the presence of meat alternatives on the food market and the ongoing shift towards plant-based diets there is a need for continuous monitoring to keep the occurrence at safe levels. More attention is needed from the regulatory side for policymakers to consider the legislations of mycotoxins in meat alternatives.

The Effects of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 on Oxidative Stress-Related Genes in the Kidneys of Laying Hens.

In the context of nephrotoxic risks associated with environmental contaminants, this study focused on the impact of mycotoxin exposure on the renal health of laying hens, with particular attention to oxidative stress pathways. Sixty laying hens were assigned to three groups-a control group (CON), a low-dose mycotoxin group (LOW), and a high-dose mycotoxin group (HIGH)-and monitored for 72 h. Mycotoxin contamination involved T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 at their EU-recommended levels (low mix) and at double doses (high mix). Clinical assessments revealed no signs of toxicity or notable weight changes. Analysis of the glutathione redox system parameters demonstrated that the reduced glutathione content was lower than that in the controls at 48 h and higher at 72 h. Glutathione peroxidase activity increased in response to mycotoxin exposure. In addition, the gene expression patterns of key redox-sensitive pathways, including Keap1-Nrf2-ARE and the AhR pathway, were examined. Notably, gene expression profiles revealed dynamic responses to mycotoxin exposure over time, underscoring the intricate interplay of redox-related mechanisms in the kidney. This study sheds light on the early effects of mycotoxin mixtures on laying hens' kidneys and their potential for oxidative stress.

Antagonistic properties against Fusarium sporotrichioides and glycosylation of HT-2 and T-2 toxins by selected Trichoderma strains.

The present study assessed the ability of Trichoderma to combat F. sporotrichioides, focusing on their antagonistic properties. Tests showed that Trichoderma effectively inhibited F. sporotrichioides mycelial growth, particularly with T. atroviride strains. In co-cultures on rice grains, Trichoderma almost completely reduced the biosynthesis of T-2 and HT-2 toxins by Fusarium. T-2 toxin-α-glucoside (T-2-3α-G), HT-2 toxin-α-glucoside (HT-2-3α-G), and HT-2 toxin-ß-glucoside (HT-2-3ß-G) were observed in the common culture medium, while these substances were not present in the control medium. The study also revealed unique metabolites and varying metabolomic profiles in joint cultures of Trichoderma and Fusarium, suggesting complex interactions. This research offers insights into the processes of biocontrol by Trichoderma, highlighting its potential as a sustainable solution for managing cereal plant pathogens and ensuring food safety.

Electrochemical microfluidic immunosensor with graphene-decorated gold nanoporous for T-2 mycotoxin detection.

T-2 is one of the most potent cytotoxic food-borne mycotoxins. In this work, we have developed and characterized an electrochemical microfluidic immunosensor for T-2 toxin quantification in wheat germ samples. T-2 toxin detection was carried out using a competitive immunoassay method based on monoclonal anti-T-2 antibodies immobilized on the poly(methyl methacrylate) (PMMA) microfluidic central channel. The platinum wire working electrode at the end of the channel was in situ modified by a single-step electrodeposition procedure with reduced graphene oxide (rGO)-nanoporous gold (NPG). T-2 toxin in the sample was allowed to compete with T-2-horseradish peroxidase (HRP) conjugated for the specific recognizing sites of immobilized anti-T-2 monoclonal antibodies. The HRP, in the presence of hydrogen peroxide (H2O2), catalyzes the oxidation of 4-tert-butylcatechol (4-TBC), whose back electrochemical reduction was detected on the nanostructured electrode at -0.15 V. Thus, at low T-2 concentrations in the sample, more enzymatically conjugated T-2 will bind to the capture antibodies, and, therefore, a higher current is expected. The detection limits found for electrochemical immunosensor, and commercial ELISA procedure were 0.10 µg kg-1 and 10 µg kg-1, and the intra- and inter-assay coefficients of variation were below 5.35% and 6.87%, respectively. Finally, our microfluidic immunosensor to T-2 toxin will significantly contribute to faster, direct, and secure in situ analysis in agricultural samples.

Betulinic acid attenuates T-2 toxin-induced lung injury by activating Nrf2 signaling pathway and inhibiting MAPK/NF-κB signaling pathway.

T-2 toxin, a type-A trichothecene mycotoxin, exists ubiquitously in mildewed foods and feeds. Betulinic acid (BA), a pentacyclic triterpenoid derived from plants, has the effect of relieving inflammation and oxidative stress. The purpose of this study was to investigate whether BA mitigates lung impairment caused by T-2 toxin and elucidate the underlying mechanism. The results indicated that T-2 toxin triggered the inflammatory cell infiltration, morphological alterations and cell apoptosis in the lungs. It is gratifying that BA ameliorated T-2 toxin-caused lung injury. The protein expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway and the markers of antioxidative capability were improved in T-2 toxin induced lung injury by BA mediated protection. Simultaneously, BA supplementation could suppress T-2 toxin-induced mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB)-dependent inflammatory response and mitochondrial apoptotic pathway. Therefore, T-2 toxin gave rise to pulmonary toxicity, but these changes were moderated by BA administration through regulation of the Nrf2/MAPK/NF-κB pathway, which maybe offer a viable alternative for mitigating the lung impairments caused by the mycotoxin.

HIF-1α is a "brake" in JNK-mediated activation of amyloid protein precursor and hyperphosphorylation of tau induced by T-2 toxin in BV2 cells.

Mycotoxins have been shown to activate multiple mechanisms that may potentially lead to the progression of Alzheimer's disease (AD). Overexpression/aberrant cleavage of amyloid precursor protein (APP) and hyperphosphorylation of tau (P-tau) is hallmark pathologies of AD. Recent advances suggest that the neurotoxic effects of mycotoxins involve c-Jun N-terminal kinase (JNK) and hypoxia-inducible factor-1α (HIF-1α) signaling, which are closely linked to the pathogenesis of AD. Due to the high toxicity and broad contamination of T-2 toxin, we assessed how T-2 toxin exposure alters APP and P-tau formation in BV2 cells and determined the underlying roles of HIF-1α and JNK signaling. The findings revealed that T-2 toxin stimulated the expression of HIF-1α and hypoxic stress factors in addition to increasing the expression of APP and P-tau. Additionally, HIF-1α acted as a "brake" on the induction of APP and P-tau expression by negatively regulating these proteins. Notably, T-2 toxin activated JNK signaling, which broke this "brake" to promote the formation of APP and P-tau. Furthermore, the cytoskeleton was an essential target for T-2 toxin to exert cytotoxicity, and JNK/HIF-1α participated in this damage. Collectively, when the T-2 toxin induces the production of APP and P-tau, JNK might interfere with HIF-1α's protective function. This study will provide clues for further research on the neurotoxicity of mycotoxins.

Debunking the Myth of Fusarium poae T-2/HT-2 Toxin Production.

Fusarium poae is commonly detected in field surveys of Fusarium head blight (FHB) of cereal crops and can produce a range of trichothecene mycotoxins. Although experimentally validated reports of F. poae strains producing T-2/HT-2 trichothecenes are rare, F. poae is frequently generalized in the literature as a producer of T-2/HT-2 toxins due to a single study from 2004 in which T-2/HT-2 toxins were detected at low levels from six out of forty-nine F. poae strains examined. To validate/substantiate the observations reported from the 2004 study, the producing strains were acquired and phylogenetically confirmed to be correctly assigned as F. poae; however, no evidence of T-2/HT-2 toxin production was observed from axenic cultures. Moreover, no evidence for a TRI16 ortholog, encoding a key acyltransferase shown to be necessary for T-2 toxin production in other Fusarium species, was observed in any of the de novo assembled genomes of the F. poae strains. Our findings corroborate multiple field-based and in vitro studies on FHB-associated Fusarium populations which also do not support the production of T-2/HT-2 toxins with F. poae and therefore conclude that F. poae should not be generalized as a T-2/HT-2 toxin producing species of Fusarium.

Fusarium sporotrichioides Produces Two HT-2-α-Glucosides on Rice.

Fusarium is a genus that mostly consists of plant pathogenic fungi which are able to produce a broad range of toxic secondary metabolites. In this study, we focus on a type A trichothecene-producing isolate (15-39) of Fusarium sporotrichioides from Lower Austria. We assessed the secondary metabolite profile and optimized the toxin production conditions on autoclaved rice and found that in addition to large amounts of T-2 and HT-2 toxins, this strain was able to produce HT-2-glucoside. The optimal conditions for the production of T-2 toxin, HT-2 toxin, and HT-2-glucoside on autoclaved rice were incubation at 12 °C under constant light for four weeks, darkness at 30 °C for two weeks, and constant light for three weeks at 20 °C, respectively. The HT-2-glucoside was purified, and the structure elucidation by NMR revealed a mixture of two alpha-glucosides, presumably HT-2-3-O-alpha-glucoside and HT-2-4-O-alpha-glucoside. The efforts to separate the two compounds by HPLC were unsuccessful. No hydrolysis was observed with two the alpha-glucosidases or with human salivary amylase and Saccharomyces cerevisiae maltase. We propose that the two HT-2-alpha-glucosides are not formed by a glucosyltransferase as they are in plants, but by a trans-glycosylating alpha-glucosidase expressed by the fungus on the starch-containing rice medium.

Melatonin alleviates T-2 toxin-induced oxidative damage, inflammatory response, and apoptosis in piglet spleen and thymus.

T-2 toxin, an unavoidable contaminant in animal feeds, can induce oxidative stress and damage immune organs. Melatonin (MT), a natural and potent antioxidant, has shown promise as a detoxifier for various mycotoxins. However, the detoxifying effect of MT on T-2 toxin has not been previously reported. In order to investigate the protective effect of MT added to diets on the immune system of T-2 toxin-exposed piglets, twenty piglets weaned at 28d of age were randomly divided into control, T-2 toxin (1 mg/kg), MT (5 mg/kg), and T-2 toxin (1 mg/kg) + MT (5 mg/kg) groups(n = 5 per group). Our results demonstrated that MT mitigated T-2 toxin-induced histoarchitectural alterations in the spleen and thymus, such as hemorrhage, decreased white pulp size in the spleen, and medullary cell sparing in the thymus. Further research revealed that MT promoted the expression of Nrf2 and increased the activities of antioxidant enzymes CAT and SOD, while reducing the production of the lipid peroxidation product MDA. Moreover, MT inhibited the NF-κB signaling pathway, regulated the expression of downstream cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1. MT also suppressed the activation of caspase-3 while down-regulating the ratio of Bax/Bcl-2 to reduce apoptosis. Additionally, MT ameliorated the T-2 toxin-induced disorders of immune cells and immune molecules in the blood. In conclusion, our findings suggest that MT may effectively protect the immune system of piglets against T-2 toxin-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis in the spleen and thymus. Therefore, MT holds the potential as an antidote for T-2 toxin poisoning.

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives.

Fusarium species produce a secondary metabolite known as T-2 toxin, which is the primary and most harmful toxin found in type A trichothecenes. T-2 toxin is widely found in food and grain-based animal feed and endangers the health of both humans and animals. T-2 toxin exposure in humans and animals occurs primarily through food administration; therefore, the first organ that T-2 toxin targets is the gut. In this overview, the research progress, toxicity mechanism, and detoxification of the toxin T-2 were reviewed, and future research directions were proposed. T-2 toxin damages the intestinal mucosa and destroys intestinal structure and intestinal barrier function; furthermore, T-2 toxin disrupts the intestinal microbiota, causes intestinal flora disorders, affects normal intestinal metabolic function, and kills intestinal epidermal cells by inducing oxidative stress, inflammatory responses, and apoptosis. The primary harmful mechanism of T-2 toxin in the intestine is oxidative stress. Currently, selenium and plant extracts are mainly used to exert antioxidant effects to alleviate the enterotoxicity of T-2 toxin. In future studies, the use of genomic techniques to find upstream signaling molecules associated with T-2 enterotoxin toxicity will provide new ideas for the prevention of this toxicity. The purpose of this paper is to review the progress of research on the intestinal toxicity of T-2 toxin and propose new research directions for the prevention and treatment of T-2 toxin toxicity.

Pathological consequences, metabolism and toxic effects of trichothecene T-2 toxin in poultry.

Contamination of feed with mycotoxins has become a severe issue worldwide. Among the most prevalent trichothecene mycotoxins, T-2 toxin is of particular importance for livestock production, including poultry posing a significant threat to animal health and productivity. This review article aims to comprehensively analyze the pathological consequences, metabolism, and toxic effects of T-2 toxin in poultry. Trichothecene mycotoxins, primarily produced by Fusarium species, are notorious for their potent toxicity. T-2 toxin exhibits a broad spectrum of negative effects on poultry species, leading to substantial economic losses as well as concerns about animal welfare and food safety in modern agriculture. T-2 toxin exposure easily results in negative pathological consequences in the gastrointestinal tract, as well as in parenchymal tissues like the liver (as the key organ for its metabolism), kidneys, or reproductive organs. In addition, it also intensely damages immune system-related tissues such as the spleen, the bursa of Fabricius, or the thymus causing immunosuppression and increasing the susceptibility of the animals to infectious diseases, as well as making immunization programs less effective. The toxin also damages cellular processes on the transcriptional and translational levels and induces apoptosis through the activation of numerous cellular signaling cascades. Furthermore, according to recent studies, besides the direct effects on the abovementioned processes, T-2 toxin induces the production of reactive molecules and free radicals resulting in oxidative distress and concomitantly occurring cellular damage. In conclusion, this review article provides a complex and detailed overview of the metabolism, pathological consequences, mechanism of action as well as the immunomodulatory and oxidative stress-related effects of T-2 toxin. Understanding these effects in poultry is crucial for developing strategies to mitigate the impact of the T-2 toxin on avian health and food safety in the future.

Molecular Engineering and Confinement Effect Powered Ultrabright Nanoparticles for Improving Sensitivity of Lateral Flow Immunoassay.

The application of traditional lateral flow immunoassay (LFIA)-based gold nanoparticles (AuNPs) to measure traces of target chemicals is usually challenging. In this study, we developed an integrated strategy based on molecular engineering and the spatial confinement of nanoparticles (NPs) to obtain ultrahigh quantum yields (QYs) of aggregation-induced emission (AIE) fluorescence NPs and employed them for the highly sensitive detection of T-2 toxin on the LFIA platform. Tetraethyl-4,4',4″,4‴-(ethene-1,1,2,2-tetrayl)tetrabenzoate (TCPEME), an AIE luminogen, was designed using molecular engineering to lower the energy gap, achieving higher QYs (26.26%) than previous AIEgens (13.02%). Subsequently, TCPEME-doped fluorescence NPs (TFNPs) achieved ultrahigh QYs, up to 84.55%, which were generated from the strong restriction of the NP state, efficiently suppressing nonradiative relaxation channels verified by ultrafast electron dynamics. On the LFIA platform, the sensitivity of the designed TFNP-based LFIA (TFNP-LFIA) was 10.4-fold and 4.3-fold more sensitive than that of the AuNP-LFIA and TPENP-LFIA for detecting the T-2 toxin, respectively. In addition, TFNP-LFIA was used for detecting T-2 toxin in samples and showed satisfactory recoveries (79.5 to 122.0%) with CV (1.49 to 11.75%), which implied excellent application potential for TFNP-LFIA. Overall, dual improvement of the molecule in fluorescence performance originating from the molecular engineering and spatial confinement of NPs could be an efficient tool for promoting the development of high-performance reporters in LFIA.

Investigation of the effects of T-2 toxin in chicken-derived three-dimensional hepatic cell cultures.

Despite being one of the most common contaminants of poultry feed, the molecular effects of T-2 toxin on the liver of the exposed animals are still not fully elucidated. To gain more accurate understanding, the effects of T-2 toxin were investigated in the present study in chicken-derived three-dimensional (3D) primary hepatic cell cultures. 3D spheroids were treated with three concentrations (100, 500, 1000 nM) of T-2 toxin for 24 h. Cellular metabolic activity declined in all treated groups as reflected by the Cell Counting Kit-8 assay, while extracellular lactate dehydrogenase activity was increased after 500 nM T-2 toxin exposure. The levels of oxidative stress markers malondialdehyde and protein carbonyl were reduced by the toxin, suggesting effective antioxidant compensatory mechanisms of the liver. Concerning the pro-inflammatory cytokines, IL-6 concentration was decreased, while IL-8 concentration was increased by 100 nM T-2 toxin exposure, indicating the multifaceted immunomodulatory action of the toxin. Further, the metabolic profile of hepatic spheroids was also modulated, confirming the altered lipid and amino acid metabolism of toxin-exposed liver cells. Based on these results, T-2 toxin affected cell viability, hepatocellular metabolism and inflammatory response, likely carried out its toxic effects by affecting the oxidative homeostasis of the cells.

Review of neurotoxicity of T-2 toxin.

T-2 toxin is a representative trichothecene that is widely detected in corn, wheat and other grain feeds. T-2 toxin has stable physical and chemical properties, making it difficult to remove from food and feed. Hence, T-2 toxin has become an unavoidable pollutant in food for humans and animals. T-2 toxin can enter brain tissue by crossing the blood-brain barrier and leads to congestion, swelling and even apoptosis of neurons. T-2 toxin poisoning can directly lead to clinical symptoms (anti-feeding reaction and decline of learning and memory function in humans and animals). Maternal T-2 toxin exposure also exerted toxic effects on the central nervous system of offspring. Oxidative stress is the core neurotoxicity mechanism underlying T-2 toxin poison. Oxidative stress-mediated apoptosis, mitochondrial oxidative damage and inflammation are all involved in the neurotoxicity induced by T-2 toxin. Thus, alleviating oxidative stress has become a potential target for relieving the neurotoxicity induced by T-2 toxin. Future efforts should be devoted to revealing the neurotoxic molecular mechanism of T-2 toxin and exploring effective therapeutic drugs to alleviate T-2 toxin-induced neurotoxicity.