Key Role of Porcine Cytochrome P450 2A19 in the Bioactivation of Aflatoxin B₁ in the Liver

The metabolic transformation of aflatoxin B1 (AFB1) in pigs remains understudied, presenting a gap in our toxicological understanding compared with extensive human-based research. Here, we found that the main products of AFB1 in porcine liver microsomes (PLMs) were AFB1-8,9-epoxide (AFBO), the generation of which correlated strongly with the protein levels and activities of cytochrome P450 (CYP)3A and CYP2A. In addition, we found that porcine CYP2A19 can transform AFB1 into AFBO, and its metabolic activity was stronger than the other CYPs we have reported, including CYP1A2, CYP3A29, and CYP3A46. Furthermore, we stably transfected all identified CYPs in HepLi cells and found that CYP2A19 stable transfected HepLi cells showed more sensitivity in AFB1-induced DNA adducts, DNA damage, and γH2AX formation than the other three stable cell lines. Moreover, the CYP2A19 N297A mutant that lost catalytic activity toward AFB1 totally eliminated AFB1-induced AFB1-DNA adducts and γH2AX formations in CYP2A19 stable transfected HepLi cells. These results indicate that CYP2A19 mainly mediated AFB1-induced cytotoxicity through metabolizing AFB1 into a highly reactive AFBO, promoting DNA adduct formation and DNA damage, and lastly leading to cell death. This study advances the current understanding of AFB1 bioactivation in pigs and provides a promising target to reduce porcine aflatoxicosis

Direct Synthesis of Large-Scale <i>Ortho</i>-Iodinated Perylene Diimides: Key Precursors for Functional Dyes

A highly regioselective tetra-<i>ortho</i>-iodination reaction of perylene diimides (PDIs) has been developed, which could be conducted on a multigram scale (>10 g), featuring a column chromatography-free workup and purification. The <i>ortho</i>-iodinated-PDIs serve as key intermediates for the preparation of a variety of <i>ortho</i>-functionalized PDIs and PDI-based conjugated polymers

Preparation of 5′-O-(1-Thiotriphosphate)-Modified Oligonucleotides Using Polymerase-Endonuclease Amplification Reaction (PEAR)

<div><p>Antisense oligonucleotides (ASODNs) have been widely used as an important tool for regulating gene expression, and developed into therapeutics. Natural ODNs are susceptible to nuclease degradation, nucleic acid analogues, however, have less side effects, stronger stability and more potent activities. Large-scale <i>de novo</i> synthesis of a certain oligonucleotide has been very difficult and costly. In a previous preliminary study, we developed the polymerase-endonuclease amplification reaction (PEAR) for amplification and large-scale preparation of natural antisense ODNs. Here we extended the method in preparation of a widely used modified oligonucleotide with 5′-O-(1-Thiotriphosphate) modifications. Using electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS) detection, the purity of the PEAR product was measured as high as 100.0%. Using PEAR a large amount of a specific oligonucleotide can be produced starting from a small amount of synthetic seeds. It is suggested that PEAR can be a useful tool for large-scale production of modified oligonucleotides.</p></div

Molecular structure representation of dNTPαSs.

<p>Molecular structure representation of dNTPαSs.</p

The LC/UV Chromatogram and Deconvoluted Mass Spectrum of the *A*G PEAR product.

<p>Components: (A) RT = 7.45 min: MW = 6742.0; (B) RT = 8.00 min; (C) RT = 8.38 min; (D) RT = 8.76 min; (E) RT = 9.05 min; See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067558#pone.0067558.s001" target="_blank">Table S2 in File S1</a> for detailed characterization of components.</p

Additional file 1: of Defective autophagy leads to the suppression of stem-like features of CD271+ osteosarcoma cells

Cell viaiblities of OS cells after chemotherapeutics treatments. (A, B) The indicated SaoS2 and MNNG/HOS cells were treated with Cisplatin (A) or Epicubicin (B) of different doses for 48 h. Then, the cell viability of the indicated cells was detected by CCK8 assay. The data are showen as the mean ± S.D. (n = 3). (PPTX 232 kb

Vanadium Dioxide Nanosheets Supported on Carbonized Cotton Fabric as Bifunctional Textiles for Flexible Pressure Sensors and Zinc-Ion Batteries

Flexible pressure sensors and aqueous batteries have been widely used in the rapid development of wearable electronics. The synergistic functionalities of versatile materials with multidimensional architectures are recognized to have a significant impact on the performance of flexible electronics. Herein, a facile hydrothermal strategy was demonstrated to conformally grow vanadium dioxide nanosheets on carbonized cotton fabrics (VO2/CCotton), which is a candidate material used in flexible piezoresistive sensors. As a result, the VO2/CCotton-based pressure sensor behaved with high sensitivity (S = 7.12 kPa–1 in the pressure range of 0–2.0 kPa) and a stable sensing ability in a wide pressure scale of 0–120 kPa. Further practical applications were performed in monitoring delicate physiological signals as well, such as twisting, blowing, and voice vibration recognitions. In addition, another application for energy storage was investigated as well. A quasi-solid-state aqueous zinc-ion battery was assembled with VO2/CCotton as the cathode and a film of Zn nanosheets/carbon nanotube as the anode. A capacity as high as 301.5 mAh g–1 and remarkable durability of 88.7% capacity retention after 5000 cycles at 10 A g–1 were found. These exceptional outcomes are attributed to the unique three-dimensional architecture and the prominent synergetic effects of CCotton and VO2 and allow for the proposal of novel guidelines for next-generation multifunctional flexible electronics

Table_1_Seasonal drivers of productivity and calcification in the coral Platygyra carnosa in a subtropical reef.docx

Scleractinian corals are increasingly subjected to local stressors combined with global changes. In subtropical areas, corals exhibit metabolic plasticity and resilience in response to variability and extremes in local temperature, salinity, and light; however, the physiological mechanisms by which corals acclimate or adapt to these changing conditions remain disputed. We assessed the physiological status of the coral Platygyra carnosa during a two-year in situ monitoring survey. To obtain metabolic rates (respiration and photosynthesis), photochemical efficiency (Fv / Fm), and biocalcification measurements, non-invasive techniques such as underwater respirometry, Pulse Amplitude Modulated (PAM) fluorometry, total alkalinity measurements, and digital photography were used. Our findings show clear seasonality in water quality parameters, which affected coral health. Elevated temperatures during the summer were below the maximum monthly mean < 31°C) but reduced the energetic productivity of corals (-44% relative to winter). Fluctuations in salinity (25–38 ppt) and pH (7.65–8.44) were linked to rainfall and reduced calcification rates. The conditions during the spring were favorable for coral metabolism and calcification (+20% relative to summer). Overall, our research demonstrates that the metabolic plasticity of P. carnosa in response to shifts in seawater quality allows this species to survive ongoing environmental change. Our in situ observations provide fundamental insights into coral response mechanisms under changing environmental conditions and contribute to projections of coral health under future scenarios of global change.</p

Data_Sheet_1_Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection.docx

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.</p