Mouse Rad1 deletion enhances susceptibility for skin tumor development

Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. To address this question, we constructed mice with a deletion of Mrad1. Matings between heterozygous Mrad1 mutant mice produced Mrad1+/+ and Mrad1+/- but no Mrad1-/- progeny, suggesting the Mrad1 null is embryonic lethal. Mrad1+/- mice demonstrated no overt abnormalities up to one and half years of age. DMBA-TPA combinational treatment was used to induce tumors on mouse skin. Tumors were larger, more numerous, and appeared earlier on the skin of Mrad1+/- mice compared to Mrad1+/+ animals. Keratinocytes isolated from Mrad1+/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1+/+ control cells. These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells

Optimization and Implementation of a Collaborative Learning Algorithm for an AI-Enabled Real-time Biomedical System

Recent years have witnessed a rapid growth of Artificial Intelligence (AI) in biomedical fields. However, an accurate and secure system for pneumonia detection and diagnosis is urgently needed. We present the optimization and implementation of a collaborative learning algorithm for an AI-Enabled Real-time Biomedical System (AIRBiS), where a convolution neural network is deployed for pneumonia (i.e., COVID-19) image classification. With augmentation optimization, the federated learning (FL) approach achieves a high accuracy of 95.66%, which outperforms the conventional learning approach with an accuracy of 94.08%. Using multiple edge devices also reduces overall training time

Robust Vehicle-to-Grid Energy Trading Method Based on Smart Forecast and Multi-Blockchain Network

In the present era, energy issues are a significant concern, and the energy trading market is the crucial sector to facilitate supply-demand balance and sustainable development. For better demand response and grid balancing, vehicle-to-grid (V2G) technology is rapidly gaining importance in energy markets. To narrow the gap between ideal V2G goals and actual applications needs, energy trading system has to overcome the challenges of over-centralized structure, inflexible timeline adaptation, limited market scale and energy efficiency, excessive feedback time costs, and low rate of economic return. To address these issues and ensure a secure energy market, we propose a decentralized intelligent V2G system called V2G Forecasting and Trading Network (V2GFTN) to achieve efficient and robust energy trading in campus EV networks. A multiple blockchain structure is proposed in V2GFTN to ensure trading security and data privacy between energy requests and offers. V2GFTN also integrates energy forecasting functions for EVs with a smart energy trading and EV allocation mechanism called SRET so that the EVs with driving tasks can supply their extra power back to the grid and achieve higher energy efficiency and economic profit. Through rigorous experimentation and compared with equivalent studies, V2GFTN system has demonstrated higher economic profit and energy demand fill rate by up to 1.6 times and 1.9 times than the state-of-the-art V2G approaches

Size-Dependent Impact of Magnetic Nanoparticles on Growth and Sporulation of Aspergillus niger

Magnetic nanoparticles (MNPs) are becoming important DNA nanocarriers for genetic engineering of industrial fungi. However, the biological effect of MNPs on industrial fungi remains unknown. In this study, we prepared three kinds of magnetic nanoparticles with different sizes (i.e., 10 nm, 20 nm, and 200 nm) to investigate their impact on the growth and sporulation of the important industrial fungus Aspergillus niger. Transmission electron microscopy, X-ray diffraction analysis and Zeta potential analysis revealed that the three kinds of MNPs, including MNP10, MNP20 and MNP200, had uniform size distribution, regular Fe3O4 X-ray diffraction (XRD) patterns and similar Zeta potentials. Interestingly, although the three kinds of MNPs did not obviously inhibit growth of the fungus, the MNP20 at 500 mg/L strongly attenuated sporulation, leading to a remarkable decrease in spore numbers on culturing plates. Further investigation showed that MNP20 at the high concentration led to drastic chitin accumulation in the cell wall, indicating cell wall disruption of the MNP20-treated fungal cells. Moreover, the MNPs did not cause unusual iron dissolution and reactive oxygen species (ROS) accumulation, and the addition of ferrous ion, ferric ion or the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) had no impact on the sporulation of the fungus, suggesting that both iron dissolution and ROS accumulation did not contribute to attenuated sporulation by MNP20. This study revealed the size-dependent effect of MNPs on fungal sporulation, which was associated with MNP-induced cell wall disruption

Diminished α7 nicotinic acetylcholine receptor (α7nAChR) rescues amyloid-β induced atrial remodeling by oxi-CaMKII/MAPK/AP-1 axis-mediated mitochondrial oxidative stress

The potential coexistence of Alzheimer's disease (AD) and atrial fibrillation (AF) is increasingly common as aging-related diseases. However, little is known about mechanisms responsible for atrial remodeling in AD pathogenesis. α7 nicotinic acetylcholine receptors (α7nAChR) has been shown to have profound effects on mitochondrial oxidative stress in both organ diseases. Here, we investigate the role of α7nAChR in mediating the effects of amyloid-β (Aβ) in cultured mouse atrial cardiomyocytes (HL-1 cells) and AD model mice (APP/PS1). In vitro, apoptosis, oxidative stress and mitochondrial dysfunction induced by Aβ long-term (72h) in HL-1 cells were prevented by α-Bungarotoxin(α-BTX), an antagonist of α7nAChR. This cardioprotective effect was due to reinstating Ca2+ mishandling by decreasing the activation of CaMKII and MAPK signaling pathway, especially the oxidation of CaMKII (oxi-CaMKII). In vivo studies demonstrated that targeting knockdown of α7nAChR in cardiomyocytes could ameliorate AF progression in late-stage (12 months) APP/PS1 mice. Moreover, α7nAChR deficiency in cardiomyocytes attenuated APP/PS1-mutant induced atrial remodeling characterized by reducing fibrosis, atrial dilation, conduction dysfunction, and inflammatory mediator activities via suppressing oxi-CaMKII/MAPK/AP-1. Taken together, our findings suggest that diminished α7nAChR could rescue Aβ-induced atrial remodeling through oxi-CaMKII/MAPK/AP-1-mediated mitochondrial oxidative stress in atrial cells and AD mice

Synthesis of Phenylboronic Acid-Functionalized Magnetic Nanoparticles for Sensitive Soil Enzyme Assays

Soil enzymes, such as invertase, urease, acidic phosphatase and catalase, play critical roles in soil biochemical reactions and are involved in soil fertility. However, it remains a great challenge to efficiently concentrate soil enzymes and sensitively assess enzyme activity. In this study, we synthesized phenylboronic acid-functionalized magnetic nanoparticles to rapidly capture soil enzymes for sensitive soil enzyme assays. The iron oxide magnetic nanoparticles (MNPs) were firstly prepared by the co-precipitation method and then functionalized by (3-aminopropyl)triethoxysilane, polyethyleneimine and phenylboric acid in turn, obtaining the final nanoparticles (MNPPBA). Protein-capturing assays showed that the functionalized MNPs had a much higher protein-capturing capacity than the naked MNPs (56% versus 6%). Moreover, MNPPBA almost thoroughly captured the tested enzymes, i.e., urease, invertase, and alkaline phosphatase, from enzyme solutions. Based on MNPPBA, a soil enzyme assay method was developed by integration of enzyme capture, magnetic separation and trace enzyme analysis. The method was successfully applied in determining trace enzyme activity in rhizosphere soil. This study provides a strategy to sensitively determine soil enzyme activity for mechanistic investigation of soil fertility and plant–microbiome interaction

Enhancers Improve the AID-Induced Hypermutation in Episomal Vector for Antibody Affinity Maturation in Mammalian Cell Display

The induction of somatic hypermutation (SHM) in various cell lines by activation-induced cytidine deaminase (AID) has been used in protein-directed selection, especially in antibody affinity maturation. Several antibody affinity maturation systems based on mammalian cells have been developed in recent years, i.e., 293T, H1299, Raji and CHO cells. However, the efficiency of in vitro AID-induced hypermutation is low, restricting the application of such systems. In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. The plasmid containing the two enhancers exhibited two-fold improvement of mutation rate over pCEP4 in an AID expression H1299 cell line (H1299-AID). With the engineered episomal vector, we improved the affinity of this antibody in H1299-AID cells by 20-fold

Mouse <it>Rad1 </it>deletion enhances susceptibility for skin tumor development

Abstract Background Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. Results To address this question, we constructed mice with a deletion of Mrad1. Matings between heterozygous Mrad1 mutant mice produced Mrad1+/+ and Mrad1+/- but no Mrad1-/- progeny, suggesting the Mrad1 null is embryonic lethal. Mrad1+/- mice demonstrated no overt abnormalities up to one and half years of age. DMBA-TPA combinational treatment was used to induce tumors on mouse skin. Tumors were larger, more numerous, and appeared earlier on the skin of Mrad1+/- mice compared to Mrad1+/+ animals. Keratinocytes isolated from Mrad1+/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1+/+ control cells. Conclusion These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells.</p

Inactivation of E. coli, S. aureus, and Bacteriophages in Biofilms by Humidified Air Plasma

In this study, humidified air dielectric barrier discharge (DBD) plasma was used to inactivate Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and bacteriophages in biofilms containing DNA, NaCl, carbohydrates, and proteins. The humidified DBD plasma was very effective in the inactivation of microbes in the (&le;1.0 &mu;m) biofilms. The number of surviving E. coli, S. aureus, and bacteriophages in the biofilms was strongly dependent on the constituent and thickness of the biofilms and was greatly reduced when the plasma treatment time increased from 5 s to 150 s. Our analysis shows that the UV irradiation was not responsible for the inactivation of microbes in biofilms. The short-lived RONS generated in the humidified air DBD plasma were not directly involved in the inactivation process; however, they recombined or reacted with other species to generate the long-lived RONS. Long-lived RONS diffused into the biofilms to generate very active species, such as ONOOH and OH. This study indicates that the geminated NO2 and OH pair formed due to the homolysis of ONOOH can cause the synergistic oxidation of various organic molecules in the aqueous solution. Proteins in the biofilm were highly resistant to the inactivation of microbes in biofilms, which is presumably due to the existence of the unstable functional groups in the proteins. The unsaturated fatty acids, cysteine-rich proteins, and sulfur&ndash;methyl thioether groups in the proteins were easily oxidized by the geminated NO2 and OH pair