Inhibition of Fungal Aflatoxin B1 Biosynthesis by Diverse Botanically-Derived Polyphenols

Purpose: To identify and characterize the capacity of diverse botanically-derived polyphenols to inhibit aflatoxin B1 (AFB1) production by Aspergillus flavus.Methods: A tea-derived polyphenol mixture and numerous individual polyphenols were tested for their effects on A. flavus growth and AFB1 production. Fungal spores were cultured for 60 h with polyphenols (range 0 ‒ 1,000 μg/mL). The fungi were enumerated by hemocytometry, and AFB1 in culture supernatants was quantified by high-performance liquid chromatography (HPLC).Results: Neither the tea-derived polyphenol mixture nor individual polyphenol compound, except quercetin, inhibited A. flavus growth. Quercetin detectably inhibited growth at 800 μg/mL; none of the remaining polyphenols inhibited fungal proliferation, even at 1,000 μg/mL. However, catechin mixture and all individual polyphenols differentially inhibited fungal AFB1 biosynthesis. Non-ester catechin derivatives revealed stronger inhibitory activity than ester derivatives.Conclusion: Quercetin exhibits the strongest inhibitory effect on AFB1 production and is the only test compound that also inhibits fungal proliferation. Botanically-derived polyphenols are, therefore, promising reagents for controlling fungal contamination and associated toxic aflatoxin deposition in harvested crops and in food processing operations.Keywords: Polyphenols, Quercetin, Aflatoxin B1, Inhibition, Antioxidatio

A Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease

APOE ε4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and accounts for 50-65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE ε4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE ε4 stratification. Two specific modules were identified in AD APOE ε4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE ε4 carriers were ISOC1, ENO3, GDF10, GNB3, XPO4, ACLY and MATN2. The other module of AD APOE ε4 carriers consisted of 10 hub genes including ANO3, ARPP21, HPCA, RASD2, PCP4 and ADORA2A. The module of AD APOE ε4 non-carriers consisted of 16 hub genes including DUSP5, TNFRSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE ε4 carriers including ISOC1 and ENO3 and the module of non-carriers contained the most highly connected hub gene clusters. mRNA expression of the genes in the cluster of the ISOC1 and ENO3 module of carriers was shown to be correlated in a time-dependent manner under APOE ε4 treatment but not under APOE ε3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers' module was correlated under APOE ε3 treatment but not under APOE ε4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson's disease. These data demonstrate that AD in APOE ε4 carriers involves more genetic factors and particular biological processes, whereas AD in APOE ε4 non-carriers shares more common pathways with other types of diseases. The study reveals differential genetic bases and pathogenic and pathological processes between carriers and non-carriers, providing new insight into the mechanisms of the differences between APOE ε4 carriers and non-carriers in AD.published_or_final_versio

A Double-Voltage-Controlled Effective Thermal Conductivity Model of Graphene for Thermoelectric Cooling

© 1963-2012 IEEE. Graphene provides a new opportunity for thermoelectric study based on its unique heat transfer behavior controllable by a gate voltage. In this paper, an effective thermal conductivity model of graphene for thermoelectric cooling is proposed. The model is based on a double-voltage-control mechanism. According to the law of Fourier heat conduction, an effective thermal conductivity model of the proposed thermoelectric cooling device is derived taking a tunable external voltage into account. Then, a gate voltage is used which can change graphene's thermoelectric characteristics. To verify the correctness and effectiveness of the proposed model, a circuit simulation model using HSPICE is built based on the thermoelectric duality. The simulation results from HSPICE and the calculated results from the mathematic model show good agreements with each other. This paper provides a novel precisely controlling method for thermoelectric cooling

Phenotypic and functional modulation of porcine monocyte-derived dendritic cells for foot-and-mouth disease virus

Dendritic cells (DCs) play an important role in inducing primary antigen-specific immune responses to viral antigens. In this study, the peripheral blood monocyte-derived (PBMC) were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. After 6 days of culture, immature monocyte-derived dendritic cells (Mo-DCs) were generated. The addition of lipopolysaccharide (LPS) during differentiation of Mo-DCs enhanced their ability to stimulate allogeneic mixed lymphocyte reaction (MLR) and alter their ability to produce cytokines. Then, we investigated the interaction between foot-and-mouth disease virus (FMDV) and porcine Mo-DCs in vitro and confirmed that the immunological phenotype and function of porcine Mo-DCs were modulated during FMDV infection. A down-regulated expression of MHC II and CD1 were observed at 48 h post FMDV infection. In addition, the infected porcine Mo-DCs exhibited ultrastructural morphological changes, FMDV-infected porcine Mo-DCs failed to stimulate T cell proliferation in vitro. Moreover, infection of porcine Mo-DCs in vitro induced the secretion of IFN-γ and the suppressive cytokine IL-10 in porcine Mo-DCs. Results indicated that the down-regulation of MHC II and CD1 molecules and the increased secretion of the IFN-γ and IL-10 cytokines might be the mechanisms that FMDV uses to evade the host immune responses.Key words: Dendritic cells, foot-and-mouth disease virus, MHC II, modulation, cytokines

High-Speed Photography and Digital Optical Measurement Techniques for Geomaterials: Fundamentals and Applications

Geomaterials (i.e. rock, sand, soil and concrete) are increasingly being encountered and used in extreme environments, in terms of the pressure magnitude and the loading rate. Advancing the understanding of the mechanical response of materials to impact loading relies heavily on having suitable high-speed diagnostics. One such diagnostic is high-speed photography, which combined with a variety of digital optical measurement techniques can provide detailed insights into phenomena including fracture, impact, fragmentation and penetration in geological materials. This review begins with a brief history of high-speed imaging. Section 2 discusses of the current state of the art of high-speed cameras, which includes a comparison between charge-coupled device and complementary metal-oxide semiconductor sensors. The application of high-speed photography to geomechanical experiments is summarized in Sect. 3. Section 4 is concerned with digital optical measurement techniques including photoelastic coating, Moiré, caustics, holographic interferometry, particle image velocimetry, digital image correlation and infrared thermography, in combination with high-speed photography to capture transient phenomena. The last section provides a brief summary and discussion of future directions in the field.This work was supported by the Australian Research Council (LE150100058) and Engineering Seed Funding Scheme of Monash University. The first author would like to acknowledge the financial support by the China Scholarship Council

Antifatigue Effect of Millettiae speciosae Champ (Leguminosae) Extract in Mice

Purpose: To evaluate whether Millettiae Speciosae Champ. (Leguminosae) can enhance exercise performance as well as ascertain if it a potential functional food material.Methods: The extract of Millettia speciosa Champ. (MSE) was orally administered to mice in 500, 1000, 2000 mg/kg doses to investigate its anti-fatigue effect in both forced swimming and climbing tests. Glycogen, triglyceride (TG), blood urea nitrogen (BUN) and creatine phosphokinase (CK) levels in plasma which can indicate alterations in energy utilization during exercise performance, were determined to analyze the operating exercise mechanisms.Results: The results showed that swimming time to exhaustion was longer in all treated groups (41.06 ± 1.92, 47.84 ± 1.60, 54.00 ± 2.45 min for 500, 10000 and 2000 mg/kg doses, respectively) than for control (19.45 ± 0.62 min, p < 0.05). The middle and high doses of MSE-treated groups significantly prolonged the climbing time compared with control (p < 0.05). Furthermore, MSE reduced the content of TG significantly by increasing fat utilization, delayed the accumulation of BUN and decreased the level of CK (p < 0.05). In addition, administration of MSE significantly protected the depletion of muscle glycogen when compared with control (p < 0.05).Conclusion: The results show for the first time that Millettia speciosa Champ. (Leguminosae) has significant anti-fatigue activity, and also suggest that it is a potential functional food material.Keywords: Radix millettiae speciosae, Anti-fatigue activity, Exercise performance, Serum urea nitrogen, Gastrocnemius muscle glycogen, Triglyceride, Functional foo

Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients

<p>Abstract</p> <p>Background</p> <p>Glutathione S-transferases (GSTs) play an important role in metabolizing anti-epileptic drugs (AEDs) in liver. Expressions of GSTs in brain, which may result in poor efficacy of AEDs, have not been well studied. Using clinical cortex specimen from 32 intractable epileptic subjects and 8 non-epileptic controls, the present study investigated the correlation between GSTs and intractable epilepsy.</p> <p>Results</p> <p>Three different GST isoforms (α, μ, and π) were detected with immunohistochemistry. GST-α expression was not seen in any cortex specimens. Sixty three percent (63%) of control and 53% of intractible epileptic specimens showed GST-μ immunoreactivity. No significant difference in intensity of GST-μ staining was observed between these two groups. GST-π expression was found in endothelial cells and glial cells/astrocytes. Fifty percent (50%) of the control patients and 66% of the epileptic patients were GST-π positive. The grading of epileptic patients was significantly higher than that of control patients (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>High levels of GST-π in endothelial cells and glial cells/astrocyte correlate to medical intractable epilepsy, suggesting that GST-π contributes to resistance to AED treatment.</p

RXRα acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells

Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid receptors and other hormone receptors including the orphan receptor TR3, forming different heterodimers that transduce diverse steroid/thyroid hormone signaling. Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRalpha, shuttling is energy-dependent through a nuclear pore complex (NPC)mediated pathway for its import and an intact DNA binding domain-mediated pathway for its export. In the presence of its ligand 9-cis retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More importantly, we also show that RXRalpha. acts as a carrier to assist translocation of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3 colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depends on RXRalpha as in living cells GFP-TR3 alone did not result in export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP-TR3 cotransfected with RXRalpha was exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti-sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid. In addition, mitochondrial TR3, but not RXRalpha was critical for apoptosis, as TR3 mutants that were distributed in the mitochondria induced apoptosis in the presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of RXRalpha function, in which it acts as a carrier for nucleocytoplasmic translocation of orphan receptors

Antagonism between ambient ozone increase and urbanization-oriented population migration on Chinese cardiopulmonary mortality

Ever-increasing ambient ozone (O3) pollution in China has been exacerbating cardiopulmonary premature deaths. However, the urban-rural exposure inequity has seldom been explored. Here, we assess population-scale O3 exposure and mortality burdens between 1990 and 2019 based on integrated pollution tracking and epidemiological evidence. We find Chinese population have been suffering from climbing O3 exposure by 4.3 ± 2.8 ppb per decade as a result of rapid urbanization and growing prosperity of socioeconomic activities. Rural residents are broadly exposed to 9.8 ± 4.1 ppb higher ambient O3 than the adjacent urban citizens, and thus urbanization-oriented migration compromises the exposure-associated mortality on total population. Cardiopulmonary excess premature deaths attributable to long-term O3 exposure, 373,500 (95% uncertainty interval [UI]: 240,600–510,900) in 2019, is underestimated in previous studies due to ignorance of cardiovascular causes. Future O3 pollution policy should focus more on rural population who are facing an aggravating threat of mortality risks to ameliorate environmental health injustice

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition