Characterization of the Complete Mitochondrial Genome of Pleurogenoides japonicus (Digenea, Pleurogenidae): Comparison With the Members of Microphalloidea and Phylogenetic Implications.

Pleurogenoides japonicus (Trematoda: Microphalloidea) is an important parasite in wood frogs with high infection rates and significant ecological, economic, and societal importance. The scarcity of molecular data for these parasites severely limits population genetics and phylogenetic studies. In the present study, for the first time, we determined and described the entire mitochondrial (mt) genome of P. japonicus as the first representative of the family Pleurogenidae. The entire mt genome of P. japonicus was circular, with 15,043 bp (GenBank accession number OR900118), containing 36 genes, comprising 12 protein-coding genes (cox1-3, nad1-6, nad4L, cytb, and atp6), two ribosomal RNA genes, 22 transfer RNA genes, and two non-coding regions. There were 23 intergenic spacers, ranging from 2 to 162 bp, and only one 40 bp overlap between nad4L and nad4 genes in the P. japonicus mt genome. The nucleotide composition of P. japonicus mt genome exhibited a strong AT bias with a 63.75% A + T content, while the AT- and GC-skews were - 0.435 and 0.407, respectively. Comparative analysis demonstrated that the P. japonicus mt genome shared the most common characteristics with Microphalloidea trematodes, and the cox1 gene was the longest and most conserved gene in Microphalloidea trematodes. The gene arrangements of Xiphidiata trematodes were of the same order based on protein-coding genes and rRNA genes, except for tRNA. More than two gene arrangement types exist in Echinostomata and Xiphidiata, and the gene rearrangement events mainly occurred in "trnE-trnG" and "trnG-trnE". Phylogenetic analysis suggested that trematodes of the family Pleurogenidae clustered more with Prosthogonimidae than Eucotylidae. The mt genome data of P. japonicus provide an accurate genetic marker for further studies of Xiphidiata trematodes.

Tuning Interface Mechanics Via ß-Configuration Dominant Amyloid Aggregates for Lithium Metal Batteries.

Owing to abundant polar groups and good lithiophilicity, protein materials regain interest for application in lithium metal batteries (LMBs). Current proteins with an α-conformation for modifying lithium (Li) anodes possess typically poor mechanical properties, and there is therefore a significant need for advanced protein materials. Herein, a lysozyme-modified layer is coated onto the poly(vinylidene fluoride) electrospun mat for high mechanical strength and uniform Li-ion flux. The lysozyme membrane can regulate Li+ deposition behavior due to complete ß-sheet configuration, high lithiophilicity sulfhydryl groups, and columnar nanopores. As a result, the lysozyme-modified Li metal anode exhibits a high stability performance of Li-Li symmetric cells (2800 h) and Li-LiFePO4 full cell (1450 cycles). Our strategy pushes the protein with ß-sheet configuration toward the applications of next-generation LMBs.

MXene/TiO2 Heterostructure-Decorated Hard Carbon with Stable Ti-O-C Bonding for Enhanced Sodium-Ion Storage.

Hard carbon (HC) has attracted considerable attention in the application of sodium-ion battery (SIB) anodes, but the poor realistic capacity and low rate performance severely hinder their practical application. Herein we report a solvent mechanochemical protocol for the in situ fabrication of the HC-MXene/TiO2 electrode by functionalizing MXene to improve the electrochemical performance of the batteries. MXene (Ti3C2Tx) with abundant oxygen-containing functional groups reacts with HC particles in the ball milling process to form a Ti-O-C covalent cross-linked HC-MXene composite, in which the edge of the MXene nanosheets is in situ oxidized by air to form TiO2 nanorods, forming a regular 1D/2D MXene/TiO2 heterojunction structure. Ti-O-C covalent bonding can protect the heterojunction structures from pulverization and detachment from the current collector during charge/discharge cycles due to sodium-ion intercalation/detachment, thus improving the stability of the electrode structure. Meanwhile, the MXene/TiO2 heterojunction can form a 3D conductive network and provide more active sites. The resulting HC-MXene/TiO2 electrode exhibits superior electrode capacity (660 mAh g-1), making it a promising anode material for SIBs. This simple and efficient method for preparing MXene/TiO2 heterojunction-decorated HC provides a new perspective on the structural design of MXene and carbon material composites for SIBs.

Mechanistic Insights into the Structural Modulation of Transition Metal Selenides to Boost Potassium Ion Storage Stability.

Atomic-level structure engineering is an effective strategy to reduce mechanical degradation and boost ion transport kinetics for battery anodes. To address the electrode failure induced by large ionic radius of K+ ions, herein we synthesized Mn-doped ZnSe with modulated electronic structure for potassium ion batteries (PIBs). State-of-the-art analytical techniques and theoretical calculations were conducted to probe crystalline structure changes, ion/electron migration pathways, and micromechanical stresses evolution mechanisms. We demonstrate that the heterogeneous adjustment of the electronic structure can relieve the potassiumization-induced internal strain and improve the structural stability of battery anodes. Our work highlights the importance of the correlation between doping chemistry and mechanical stability, inspiring a pathway of structural engineering strategy toward a highly stable PIBs.

Reduce and concentrate graphene quantum dot size via scissors: vacancy, pentagon-heptagon and interstitial defects in graphite by gamma rays.

Graphene quantum dots (GQDs) with ultrafine particle size and centralized distribution have advantages of small size, narrow size distribution and large specific surface area, which make it be better applied in bioimaging, drug delivery and so on. In our research, we used graphite irradiated byγ-rays to successfully prepare GQDs with ultrafine particle size, narrow size distribution and high quantum yields through solvothermal method. Vacancy defects, pentagon-heptagon defects and interstitial defects were introduced to graphite structure after irradiation, which caused the abundance and concentrated distribution of defects. The defects generated by irradiation could damage the lattice structure of graphite to make it easy for introduction of C-O-C inside graphite sheets. The oxygen-containing functional groups in graphene oxide (GO) increased and centrally distributed after irradiation in graphite, especially for C-O-C group, which were beneficial for cutting of GO and grafting of functional groups in GQDs. Therefore, average size of GQDs was successfully reduced to 1.43 nm and concentrated to 0.6-2.4 nm. After irradiation in graphite, the content of carbonyl and C-N in GQDs had a promotion, which suppressed non-radiative recombination and upgraded the quantum yields to 13.9%.

Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR.

Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.

Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity.

Ribavirin has been proven to be an antiviral treatment, whereas there are still risks of hemolysis and congenital malformation. Abnormal cardiac development contributes to the occurrence and development of many heart diseases. However, there is so far no evidence that ribavirin induces human cardiac developmental toxicity. Herein, we employed the cardiac differentiation model of human induced pluripotent stem cells (hiPSCs) to determine the impact of ribavirin on heart development. Our data showed that ribavirin at clinically high concentrations (5 and 10 µM) significantly inhibited the proliferation and differentiation of hiPSCs from mesoderm to cardiac progenitor cells and cardiac progenitor cells to cardiomyocytes, but not from pluripotent status to mesoderm. Meanwhile, DCFH-DA staining revealed that ribavirin could increase ROS content in the mid-phase of differentiation. In addition, ribavirin treatment (1, 5 and 10 µM) remarkably caused DNA damage which was shown by the increase of γH2AX-positive cells and upregulation of the p53 during the differentiation of hiPSCs from mesoderm to cardiac progenitor cells. Moreover, exposuring to ribavirin (5 and 10 µM) markedly upregulated the expression of lncRNAs Gas5 in both mid-phase and late phase of differentiation and HBL1 in the mid-phase. In conclusion, our results suggest that ribavirin is detrimental in cardiac differentiation of hiPSCs, which may be associated with DNA damage, upregulated p53 and increased Gas5. It may provide the evidence for the rational clinical application of ribavirin.

m6A Methylation of Precursor-miR-320/RUNX2 Controls Osteogenic Potential of Bone Marrow-Derived Mesenchymal Stem Cells.

Methyltransferase-like 3 (METTL3) is the main enzyme for N6-methyladenosine (m6A)-based methylation of RNAs and it has been implicated in many biological and pathophysiological processes. In this study, we aimed to explore the potential involvement of METTL3 in osteoblast differentiation and decipher the underlying cellular and molecular mechanisms. We demonstrated that METTL3 is downregulated in human osteoporosis and the ovariectomized (OVX) mouse model, as well as during the osteogenic differentiation. Silence of METTL3 by short interfering RNA (siRNA) decreased m6A methylation levels and inhibited osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and reduced bone mass, and similar effects were observed in METTL3+/- knockout mice. In contrast, adenovirus-mediated overexpression of METTL3 produced the opposite effects. In addition, METTL3 enhanced, whereas METTL3 silence or knockout suppressed, the m6A methylations of runt-related transcription factor 2 (RUNX2; a key transcription factor for osteoblast differentiation and bone formation) and precursor (pre-)miR-320. Moreover, downregulation of mature miR-320 rescued the decreased bone mass caused by METTL3 silence or METTL3+/- knockout. Therefore, METTL3-based m6A modification favors osteogenic differentiation of BMSCs through m6A-based direct and indirect regulation of RUNX2, and abnormal downregulation of METTL3 is likely one of the mechanisms underlying osteoporosis in patients and mice. Thus, METTL3 overexpression might be considered a new approach of replacement therapy for the treatment of human osteoporosis.

Synergistic anti-tumor effects of arsenic trioxide and blue LED irradiation on human osteosarcoma.

Arsenic trioxide (ATO) has been well recognized as an anti-tumor agent for various human cancers. Recently, the blue light emitting diodes (LEDs)-based therapy has also been demonstrated to be potential therapeutic strategies for several cancers. However, the combination effects of ATO and blue LED on tumor suppression are still unclear. In this study, we determined whether combination of ATO and blue LED irradiation at 470 nm in wavelength exhibited superior anti-tumor activity in human osteosarcoma (OS). We observed that combination treatments of ATO and blue LED much more significantly decreased the percentages of proliferative cells, and increased apoptotic rate compared with any single treatments in U-2 OS cells. Furthermore, we found suppression of cell migration and invasion were much more pronounced in ATO plus blue LED treated group than single treated groups. Moreover, reactive oxygen species (ROS) assay and immunostaining of γ-H2A.X and p53 indicated that the combined treatments resulted in further markedly increases in ROS accumulation, DNA damage and p53 activity. Taken together, our study demonstrated synergistical anti-tumor effects of combined treatments of ATO and blue LED on human OS cells, which were associated with an increased ROS accumulation, DNA damaged mediated p53 activation.