Terahertz toroidal dipole metamaterial sensors for detection of aflatoxin B1

Terahertz metamaterial biosensors have attracted significant attention in the biological field due to their advantages of label-free,real-time and in situ detection.In this paper,a highly sensitive metamaterial sensor with semi-ring mirror symmetry based on toroidal dipole resonance is designed for a new metamaterial biosensor.It is shown that a refractive index sensitivity of 337.5 GHz per refractive index unit can be achieved under an analyte of saturated thickness near a 1.33 THz transmission dip.For biosensor samples where aflatoxin B1 is dropped on the metamaterial surface in our experiment,dip amplitudes of transmission varying from 0.1904 to 0.203 and 0.2093 are observed as aflatoxin B1 concentrations are altered from 0 to 0.001μg·ml-1 and to 0.01μg·ml-1,respectively.Furthermore,when aflatoxin B1 concentrations are 0.1μg·ml-1,1μg·ml-1,10μg·ml-1 and 100μg·ml-1,dip amplitudes of 0.2179,0.226,0.2384 and 0.2527 and dip redshifts of 10.1 GHz,20.1 GHz,27.7 GHz and 37.6 GHz are respectively observed.These results illustrate high-sensitivity,label-free detection of aflatoxin B1,enriching the applications of sensors in the terahertz domain.

Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma

BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

Surface-enhanced Raman Scattering of Aflatoxin B1 on Silver by DFT Method

The structure, electrostatic properties, and Raman spectra of aflatoxin B1 （AFB1） and AFB1-Ag complex are studied by density functional theory with B3LYP/6- 311G（d,p）/Lan12dz basis set. The results show that the surface-enhanced Raman scattering （SERS） and pre-resonance Raman spectra of AFB1-Ag complex strongly depend on the adsorption site and the excitation wavelength found to enhance 102-103 order compared to of the incident light. The SERS factors are normal Raman spectrum of AFB1 molecule due to the larger static polarizabilities of the AFB1-Ag complex, which directly results in the stronger chemical enhancement in SERS spectra. The pre-resonance Raman spectra of AFB1-Ag complex are explored at 266, 482, 785, and 1064 nm incident light wavelength, in which the enhancement factors are about 10^2-10^4, mainly caused by the charge-transfer excitation resonance. The vibrational modes are analyzed to explain the relationship between the vibrational direction and the enhanced Raman intensities.

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B1 in Rats

Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,AFB1+PCB2,and PCB2 groups.The latter two groups were administrated PCB2 intragastrically(30 mg/kg body weight)for 7 d,whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically.On the sixth day of treatment,the AFB1 and AFB1+PCB2 groups were intraperitoneally injected with AFB1(2 mg/kg).The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide(DMSO).On the eighth day,all rats were euthanized:serum and liver tissue were isolated for further examination.Hepatic histological features were assessed by hematoxylin and eosin-stained sections.Weight,organ coefficient(liver,spleen,and kidney),liver function(serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and direct bilirubin),oxidative index(catalase,glutathione,superoxide dismutase,malondialdehyde,and 8-hydroxy-2′-deoxyguanosine),inflammation factor[hepatic interleukin-6(IL-6)m RNA expression and serum IL-6],and bcl-2/bax ratio were measured.Results AFB1 significantly caused hepatic histopathological damage,abnormal liver function,oxidative stress,inflammation,and bcl-2/bax ratio reduction compared with DMSO-treated controls.Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1.Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.

GSTM1 and XRCC3 Polymorphisms:Effects on Levels of Aflatoxin B1-DNA Adducts

Objective： Aflatoxin B1 （AFB1）, which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 （GSTM1） and DNA repair gene x-ray repair cross-complementing group 3 （XRCC3）, can affect the levels of AFB1-DNA adducts in Guangxi Population （n= 966） from an AFB1-exposure area. Methods： AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP. Results： The GSTM1-null genotype [adjusted odds ratio （OR） = 2.09; 95% confidence interval （CI） = 1.61-2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs （95% CI） were 1.43 （1.08-1.89） and 2.42 （1.13-5.22）, respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference （OR = 1）, individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels （adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM）. Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts. Conclusion： These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

Aflatoxin B1, zearalenone and deoxynivalenol in feed ingredients and complete feed from different Province in China

Background： The current study was carried out to provide a reference for monitory of aflatoxin B_1（AFB_1）,zearalenone（ZEN） and deoxynivalenol（DON） contamination in feed ingredients and complete feeds were collected from different Province in China from 2013 to 2015.Methods： A total of 443 feed ingredients, including 220 corn, 24 wheat, 24 domestic distillers dried grains with soluble（DDGS）, 55 bran, 20 wheat shorts and red dog, 37 imported DDGS, 34 corn germ meal and 29 soybean meal as well as 127 complete feeds including 25 pig complete feed（powder）, 90 pig complete feed（pellet）, six duck complete feed and six cattle complete feed were randomly collected from different Province in China,respectively, by high-performance chromatography in combined with UV or fluorescence analysis.Results： The incidence rates of AFB_1, ZEN and DON contamination of feed ingredients and complete feeds were80.8, 92.3 and 93.9 %, respectively. The percentage of positive samples for DON ranged from 66.7 to 100 %.Domestic DDGS and imported DDGS presented the most serious contamination AFB_1, ZEN and DON contamination levels of feeds ranged from 61.5 to 100 %, indicated that serious contamination over the studied 3-year period.Conclusion： The current data provide clear evidence that AFB_1, ZEN and DON contamination of feed ingredients and complete feeds in different Province in China is serious and differs over past 3-year. The use of corn, domestic DDGS, imported DDGS and corn germ meal, which may be contaminated with these three mycotoxins, as animal feed may triggered a health risk for animal. Feeds are most contaminated with DON followed by ZEN and AFB_1.Mycotoxins contamination in feed ingredients and complete feeds should be monitored routinely in China.

Dietary aflatoxin B1 induces abnormal deposition of melanin in the corium layer of the chicken shank possibly via promoting the expression of melanin synthesis-related genes

San-Huang chicken is a high-quality breed in China with yellow feather, claw and break. However, the abnormal phenomenon of the yellow shank turning into green shank of San-Huang chicken has been a concern, as it seriously reduces the carcass quality and economic benefit of yellow-feathered broilers. In this study, the cause of this abnormal green skin in shank was systematically investigated. Physiological anatomy revealed that the abnormal skin in shank was primarily due to the deposition of melanin under the dermis. After analyzing multiple potential causes such as heredity(pedigree and genetic markers), environment(water quality monitoring) and feed composition(mycotoxin detection), excessive aflatoxin B1(AFB1) in feed was screened, accompanied with a higher L-dihydroxy-phenylalanine(L-DOPA)(P<0.05) and melanin content(P<0.01). So it was speculated that excessive AFB1 might be the main cause of abnormal green skin in shank. Subsequently, the further results showed that a high concentration of AFB1(>170 μg kg–1)indeed induced the abnormal green skin in shank compared to the normal AFB1 content(<10 μg kg–1), and the mRNA levels of TYR, TYRP1, MITE, MC1R and EDN3 genes related to melanin deposition would significantly up-regulate(P<0.01) and the content and activity of tyrosinase(TyR) significantly increased(P<0.05). At the same time, the content of L-DOPA and melanin deposition also increased significantly(P<0.01), which also confirmed the effect of excessive AFB1 on melanin deposition in skin of shank. Results of additional experiments revealed that the AFB1's negative effect on melanin deposition in skin of shank could last for a longer time. Taken together, the results of this study explained the occurrence and possible mechanisms of the abnormal AFB1-related green skin in shank of chickens. Excessive AFB1 in diets increased the L-DOPA content and melanin abnormal deposition in the chicken shank possibly via promoting TyR content and activity, and the expression of melanin synthesis-related genes. Furthermore, our findings once again raised the alarm of the danger of AFB1 in the broiler production.

Preparation of Immunomagnetic Beads Enrichment Kit for Detection of Aflatoxin B1

Immunomagnetic beads enrichment kit for detection of aflatoxin B1(AFB1) was prepared through reaction of AFB1 and p-phenylenediamine. The catches of AFB1 by the kit were 25 ng/mg. Furthermore, AFB1 was conducted specific reaction with competitive drugs with similar structure or function to AFB1, including aflatoxin M1, T-2 toxin, ochratoxin A, zearalenone and patulin, and no cross reaction was observed.

Aflatoxin B1 contamination in sunflower oil collected from sunflower oil refinery situated in Karnataka

In the present study, the aflatoxin B1 contamination at various stages of oil refining and in refined oil were carried out. This was subsequently compared with commercial vegetable oil samples. Among the 23 different sunflower oil samples were tested, 10 of them showed posi-tive results to AFB1 and the remaining 13 showed negative results to AFB1. All the refined oil samples were free from AFB1 contamination.

Development of a QCM (Quartz Crystal Microbalance) Biosensor to the Detection of Aflatoxin B1

In this study, we have used a direct immunoassay where the simple binding between antigen and an antibody is detected. Immunoassays were performed in a drop system, monitoring the frequency decrease of the quartz-crystal microbalance device because of mass increasing during immunoreaction. The QCM sensor was coated on both sides by gold electrodes, only one side of the crystal (liquid side) was in contact with the solution;the other side (contact side) was always dry. We tested a piezoelectric immunosensor for aflatoxin B1 (AFLA-B1) mycotoxin detection through the immo- bilization of DSP-anti-AFLAB1 antibody (AFLA-B1-Ab anti AFLAB1) on gold-coated quartz crystals (AT-cut/5 MHz). The DSP (3,3’-Dithiodipropionic-acid-di-N-hydroxysuccinimide ester) was used for the covalent attachment of the proteins. The piezoelectric crystal electrodes were pretreated by DSP for 15 min, rinsed with water and dried in a gentle flow of nitrogen gas. Then the DSP-coated crystals were installed in a sample holder and exposed to the anti-AFLAB1 antibody and to the AFLA-BI. Frequency and resistance shifts (Δf and ΔR) were measured simultaneously. Δf versus AFLA-BI concentrations in the range of 0.5 - 10 ppb exhibited a perfect linear correlation with a coefficient of above 0.998.

Lactobacillus plantarum T3 as an adsorbent of aflatoxin B1 effectively mitigates the toxic effects on mice

The accumulation of aflatoxin B1(AFB1)in the body is extremely harmful for host health.Using lactic acid bacteria(LAB)to modulate the adsorption and toxicity of AFB1 is an attractive research field.This paper aims to isolate LAB for AFB1 removal,confirm its action mechanism,investigate factors affecting adsorption,and evaluate its protection against AFB1-induced toxicity.Sixty indigenous LAB strains were evaluated for their ability to remove AFB1(1μg/ml)and Lactobacillus plantarum T3 exhibited the highest AFB1 removal rate(68.5%).The removal rates of AFB1 by inactivated L.plantarum T3 cells,peptidoglycan,and cytoderm were 84.0%,87.8%,and 77.0%respectively,indicating that L.plantarum T3 mainly removes AFB1 by cell adsorption.The stability of L.plantarum T3-AFB1 complex was assessed by determination of AFB1 residues in the artificial gastrointestinal environment after the complex was co-cultured for 1-3 h.The results revealed that the complex remained relatively stable,with an adsorption capacity of>50%.Compared to the mice induced by AFB1,oral intake of live and inactivated L.plantarum T3 can(i)efficiently enhance fecal AFB1 excretion,normalize pathology,and reduce serum levels of ALT,AST and Cr;(ii)ameliorate oxidative stress and immune imbalance by increasing the levels of GSH,IL-4,IgG,IgM,while decreasing MDA and TNF-α;(iii)restore gut homeostasis by maintaining Firmicutes/Bacteroidetes balance and promoting growth of beneficial bacteria.The results suggested that both live and inactivated L.plantarum T3 are promising adsorbents of AFB1 and could be considered as an effective and easy dietary intervention against its toxicity.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp(Ctenopharyngodon idella)

In nature,aflatoxins,especially aflatoxin B1(AFB1),are the common mycotoxins,which cause serious health problems for humans and animals.This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp(Ctenopharyngodon idella)and its mechanism.There were 1440 individual fish in total,with 6 treatments and each treatment replicated 3 times.The 6 treatments were fed a control diet with different doses of AFB1(0.04,29.48,58.66,85.94,110.43 and 146.92μg/kg diet)for 60 d.AFB1 increased myofiber diameter,as well as decreased myofiber density of grass carp muscle(P<0.05).The contents of free amino acid decreased gradually(P<0.05)as dietary AFB1 increased in the muscle of grass carp.The levels of reactive oxygen species,malonaldehyde and protein carbonyl(PC)were increased(P<0.05)with the dietary AFB1 increased.The levels of antioxidant enzyme(glutathione peroxidase,glutathione,glutathione reductase,total antioxidant capacity,anti-superoxide anion,and anti-hydroxyl radical)were decreased(P<0.05)with the dietary AFB1 increased.In addition,dietary AFB1 decreased the content of collagen,and downregulated the mRNA and protein levels of transforming growth factor-β(TGF-β)/Smads signaling pathway in grass carp muscle(P<0.05).The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle(P<0.05).Furthermore,the activities of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-9(MMP-9)were increased(P<0.05),and the protein levels of phosphorylate-38 mitogen-activated protein kinase(p-p38MAPK),phosphorylate-c-Jun N-terminal kinase,urokinase-type plasminogen activator(uPA),MMP-2 and MMP-9 were upregulated(P<0.05),but collagenⅠ,lamininβ1 and fibronectin were downregulated(P<0.05)with the dietary AFB1 increased in the muscle of grass carp.Based on the results of this study,we can draw the following conclusion:dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix(ECM)signaling pathway in grass carp.Moreover,the recommended safe limit of AFB1 in feed is no more than 26.77μg/kg diet according to the PC levels in grass carp muscle.

An overview of aflatoxin B1 biotransformation and aflatoxin M1 secretion in lactating dairy cows

Milk is considered a perfect natural food for humans and animals.However,aflatoxin B1(AFB1)contaminating the feeds fed to lactating dairy cows can introduce aflatoxin M1(AFM1),the main toxic metabolite of aflatoxins into the milk,consequently posing a risk to human health.As a result of AFM1 monitoring in raw milk worldwide,it is evident that high AFM1 concentrations exist in raw milk in many countries.Thus,the incidence of AFM1 in milk from dairy cows should not be underestimated.To further optimize the intervention strategies,it is necessary to better understand the metabolism of AFB1 and its biotransformation into AFM1 and the specific secretion pathways in lactating dairy cows.The meta-bolism of AFB1 and its biotransformation into AFM1 in lactating dairy cows are drawn in this review.Furthermore,recent data provide evidence that in the mammary tissue of lactating dairy cows,aflatoxins significantly increase the activity of a protein,ATP-binding cassette super-family G member 2(ABCG2),an efflux transporter known to facilitate the excretion of various xenobiotics and veterinary drugs into milk.Further research should focus on identifying and understanding the factors that affect the expression of ABCG2 in the mammary gland of cows.

Analysis of aflatoxin B1 in contaminated feed,media,and serum samples of Cyprinus carpio L.by high-performance liquid chromatography

Objectives:Enzyme-linked immunosorbent assay(ELISA)-,thin-layer chromatography(TLC)-,and highperformance liquid chromatography(HPLC)-sensitive methods were used for the identification of aflatoxin B1(AFB1)contaminated fish feed,media,and fish serum samples.Materials and Methods:The ELISA,TLC,and HPLC methods were validated by the quantitative and qualitative determination of AFB1 in contaminated fish feed,media,and fish blood serum samples.Results:The primary identification of AFB1 was carried out with a DOA-ELISA test kit ELISA followed by TLC with RF values 0.81,0.79,0.81,and 0.80 of AFB1-contaminated fish feed,media,and serum samples,respectively,compared with AFB1 standard.HPLC results show that the AFB1 levels in contaminated fish feed,media,and serum samples were 2.6,2.6,and 2.7 ng/mL,concentrations respectively.The level of concentrations of AFB1 was almost similar in all three samples,but slightly higher in the fish serum sample with,2.7 ng/ml.However,the present method is strongly recommended for monitoring AFB1 contamination in feed stuffs,especially in fisheries where the feed is under continuous exposure to moisture.Conclusions:This method is accurate and more sensitive when compared with routine conventional AFB1 detection methods,and is highly applicable in aquaculture and fisheries to screen the mycotoxins in fish feed.

Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking

Aflatoxin B1 toxicity is well known but the mechanism of this toxicity is still unclear. In addition, the target of the anti-aflatoxin chemopreventive drug Oltipraz remains to be identified. In this study, we employed computer aided reverse docking analysis to identify putative targets of Aflatoxin B1（AFB） and Oltipraz. The results showed that the clinically known toxic effects of AFB are related to this molecule＇s strong binding affinity for key proteins involved in cell apoptosis, hormone metabolism, immune suppression, and digestive organ function. In addition, virtual binding assay indicated that Oltipraz neutralizes the toxicity of AFB by inhibiting its biotransformation enzymes. In conclusion, the technique of reverse docking may be used to identify the specific targets of AFB and Oltipraz, and our findings could significantly accelerate the mechanistic studies of the two molecules and provide guidance for the development of anti-AFB drugs.

Development and analysis of a novel AF11-2 aptamer capable of enhancing the fluorescence of aflatoxin B1

Aflatoxin B1(AFB1)is one of the most common mycotoxins that threatens human health.As singlestranded oligonucleotides with high affinity and specificity,aptamers have incomparable effect on the targeted detection of AFB1.Herein,after 11 rounds of selection and analysis using a modified affinity chromatography-based SELEX strategy,the truncated 37 nt aptamer AF11-2 was successfully obtained.The aptamer shows good detection performance for AFB1,and can sensitively detect AFB1 in the range of 100-1000 nmol/L,with a detection limit of 42 nmol/L.In the detection of pretreated edible peanut oil samples,AF11-2 aptamer also showed a high recovery rate and good stability for AFB1,and achieved satisfactory results.In addition,AF11-2 aptamer can significantly enhance the fluorescence ability of AFB1,which is not available in traditional Afla17-2-3 aptamer.After molecular docking analysis,it was found that AF11-2 and Afla17-2-3 had different nucleotide binding sites for AFB1.Afla17-2-3 binds to the carbonyl O of AFB1,while AF11-2 binds to the pyrrolic O of AFB1,which may be the main reason that AF11-2 can enhance the fluorescence of AFB1.

A MOLECULAR EPIDEMIOLOGIC MARKER OF HEPATOCELLULAR CARCINOMA FROM AFLATOXIN B1 CONTAMINATED AREA IN THE SOUTHWEST OF GUANGXI

HCC specimens from high and low AFB1 risk areas in Guangxi showed different frequency of p53 mutational hot spot, which were 20/35 (57%) and 1/10 by DNA sequencing and 36/52 (69%) and 2/10 by RFLP analysis respectively. Their differences were significant (P<0.01). Mutational points of p53 gene induced by AFB1 mutagen almost exclusively clustered at codon 249 third nucleotide and by the form of G to T transversion only. We call it 'AFB1 mutational hot spot'. It turns out to be a significant marker for molecular epidemio logic survey to decide how many HCC and which individuals are induced by AFB1 mutagen, and if emergence of this marker in HCC is frequent in certain region it indicated that there is heavy contamination by AFB1.

Interaction of Hepatitis B Virus X Protein with the Pregnane X Receptor Enhances the Synergistic Effects of Aflatoxin B1 and Hepatitis B Virus on Promoting Hepatocarcinogenesis

Background and Aims:Hepatitis B virus(HBV)infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics,by unknown mechanisms,in the generation of hepatocellular carcinoma.The pregnane X receptor(PXR)is a key regulator of the body’s defense against xenobiotics,including xenobiotic carcinogens and clinical drugs.In this study,we aimed to investigate the molecular mechanisms of HBV X protein(HBx)-PXR signaling in the synergistic effects of chemical carcinogens in HBV-associated hepatocarcinogenesis.Methods:The expression profile of PXR-cytochrome p4503A4(CYP3A4)signaling was determined by PCR,western blotting,and tissue microarray.Cell viability and aflatoxin B1(AFB1)cytotoxicity were measured using the cell counting kit-8 assay.Target gene expression was evaluated using transient transfection and real time-PCR.The genotoxicity of AFB1 was assessed in newborn mice with a single dose of AFB1.Results:HBx enhanced the hepatotoxicity of AFB1 by activating CYP3A4 and reducing glutathione Stransferase Mu 1(GSTM1)in cell lines.Activation of PXR by pregnenolone 16α-carbonitrile increased AFB1-induced liver tumor incidence by up-regulating oncogenic KRAS to enhance interleukin(IL)-11:IL-11 receptor subunit alpha-1(IL11RA-1)-mediated inflammation in an HBx transgenic model.Conclusions:Our finding regarding AFB1 toxicity enhancement by an HBx-PXR-CYP3A4/GSTM1-KRASIL11:IL11RA signaling axis provides a rational explanation for the synergistic effects of chemical carcinogens in HBV infection-associated hepatocarcinogenesis.

Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents

Aflatoxins(AFTs)represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops.Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects,including neuro-,hepato-,nephron-,and immuno-toxicity.In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents.Aflatoxin B1(AFB1)is the most toxic congener among the 21 identified AFTs.Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans.Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes,including anxiety,lethargy disorders,depression-like behavior,cognitive,learning and memory defects,and decreased feeding behavior.Mechanistically,AFB1 exposure has been associated with lipid peroxidation,ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels.AFB1 exposure has also been shown to induce DNA damage,apoptosis,pyroptosis,and mitochondrial dysfunction in the brain tissue.Several signaling pathways,including gasdermin D,toll like receptor 2(TLR2),TLR4,Akt,NF-κB,ERK/MAPK,protein kinase C(PKC),and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death.Targeting these pathways by small molecules(e.g.,quercetin,curcumin,and gallic acid,and dimethyl fumarate),Chinese herbal extracts(e.g.,Artichoke leaf extract,Chelidonium majus ethanolic extract,pumpkin extract,and Crocus sativus L.tea),and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity.To date,the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear.In the present review,the clinical manifestations,molecular mechanisms,and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview.It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins.

An ultrasensitive time-resolved fluorescent immunoassay method for determination aflatoxins B1 in edible oil

Edible oil is one major nutritional ingredient to human and widely consumed directly. The contamination of aflatoxin B1 （AFB1） in edible oils has been attracted exten-sive efforts due to its hazard to human health and life. To avoid the digestion of edible oils contaminated by AFB1 the development of rapid and sensitive sensing method for AFB1 is required. Herein, a quantitative, sensitive and rapid method for AFB1 detection in edible oils was proposed by using ultrasensitive time-resolved fluorescent immunosensing （TRFIS） method. This method poses unique advantages from both time-resolved fluorescent sens-ing method and immunochromatographic assay format. The nanospheres were modified with fluorescent europium and then captured the home-made monoclonal antibody against AFB1 （3G1）. After optimization, by using a competitive immunosensing manner, this TRFIS method has a detectable linear range of 0.54-20.0 μg/kg with minimum detectable concen-tration of 0.18μg/kg. It can be completed merely within 10 min with recovery from 87.0% to 121.9%. The agreement was observed between the results by TRFIS and high perfor-mance liquid chromatography （HPLC） methods. This research provides a promising sens-ing method for sensitive and rapid determining AFB1 in edible oils.