Phylogeny and species reassessment of Hyalopterus (Aphididae,Aphidinae)

The broadly distributed genus Hyalopterus currently comprises three formally recognized species that are highly similar morphologically and hence difficult to be identified with certainty. This group has undergone multiple revisions in the past century, but none of these has assessed species from Asia, which has hampered our understanding of the species diversity within this genus. Based on a comprehensive data set from morphological data and host-associated data, and by coalescent-based delimitation approaches, the Hyalopterus species boundaries, distribution and diversity were clarified here to further reveal the composition of the species. Two single-locus (ML-GMYC and mPTP) and two multilocus (BPP and STACEY) delimitation methods were conducted based on extensive sampling. Then, the phylogenetic relationships and morphological divergence were assessed. Our data strongly supported that the number of recognized species in Hyalopterus had likely been underestimated. The phylogenetic analyses recovered four major clades, which corresponded to distinct host-plant preferences. Also, the morphological analyses showed significant differentiation for only one of the newly recognized candidate species uncovered by the delimitation approaches, suggesting the existence of at least two independent evolutionary lineages within Hyalopterus arundiniformis, which showed different patterns of host association. Moreover, based on our data, the taxonomic misidentification of H. arundiniformis in China was corrected here. This study lays the groundwork for the thorough taxonomic revision of Hyalopterus and for future evolutionary studies and underlines the importance of an integrated framework for species determination.     

CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression

CircRNAs (circular RNA) are reported to regulate onset and progress multiple cancers. Nonetheless, the function along with the underlying mechanisms of circRNAs in HER-2-positive breast cancer (BC) remains unclear. CircRNA microarrays were performed to elucidate expression profiles of HER-2-positive BC cells. circRNA levels were quantified using qRT-PCR assay. Various in vitro along with in vivo assays were employed to further explore the effects of circGFRA1 in the progress of HER-2-positive BC and interactions of circGFRA1, miR-1228 and AIFM2 in Her-2-positive BC. CircGFRA1 was remarkably upregulated in HER-2-positive BC. Knockdown of circGFRA1 could attenuate HER-2-positive BC progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. In summary, circGFRA1-miR-1228-AIFM2 axis regulates HER-2-positive BC. CircGFRA1 is a novel promising treatment option for HER-2-positive BC.     

A New 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) Derivative Overcomes Paclitaxel Resistance by Inhibiting MAPK Signaling and Increasing Paclitaxel Accumulation in Breast Cancer Cells

Tumor resistance due to multiple mechanisms seriously hinders the efficacy of chemotherapy drugs such as paclitaxel. The most widely studied P-glycoprotein inhibitors still have limited ability to reverse resistance in the clinic. In this study, NPB304, a novel Sinenxan A (SIA) derivative, was found to significantly sensitize resistant breast cancer cells to paclitaxel in vitro and in vivo. Treatment with NPB304 increased paclitaxel-induced apoptosis in a p53-dependent manner through PARP cleavage. Importantly, NPB304 enhanced the antitumor effect of paclitaxel in resistant breast tumor xenografts in nude mice without significantly affecting weight loss. NPB304 regulated cell resistance through inhibition of MAPK pathway components, including p-ERK and p-p38. Moreover, NPB304 increased paclitaxel accumulation by affecting P-gp function. In addition to increasing Rhodamine 123 accumulation, NPB304 promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model, thereby increasing the intracellular concentration of paclitaxel. Similarly, NPB304 increased the concentration of paclitaxel in the resistant tumor tissue. Hence, NPB304 is a novel compound that promotes the sensitization of resistant cells to paclitaxel through multiple mechanisms and has the potential for use in combination therapies to treat resistant breast cancer.     

Integrating Multi-Omics for Uncovering the Architecture of Cross-Talking Pathways in Breast Cancer

Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer.     

The Impacts of Dispositional Optimism and Psychological Resilience on the Subjective Well-Being of Burn Patients: A Structural Equation Modelling Analysis

Burn wounds are severely stressful events that can have a significant impact on the mental health of patients. However, the impact of burns on individuals with different personality traits can be different. The present study aimed to investigate the impact of dispositional optimism on the subjective well-being of burn patients, and mainly focused on the confirmation of the mediator role of psychological resilience. 410 burn patients from five general hospitals in Xi''an accomplished the revised Life Orientation Test, Connor-Davidson Resilience Scale, and Subjective Well-Being (SWB) scale. The results revealed that both dispositional optimism and psychological resilience were significantly correlated with SWB. Structural equation modelling indicated that psychological resilience partially mediated the relationship between dispositional optimism and SWB. The current findings extended prior reports and shed some light on how dispositional optimism influenced SWB. Limitations of the study were considered and suggestions for future studies were also discussed.     

Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53

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Complement-Related Proteins Control the Flavivirus Infection of Aedes aegypti by Inducing Antimicrobial Peptides

The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.     

Nitric oxide regulates ganoderic acid biosynthesis by the S-nitrosylation of aconitase under heat stress in Ganoderma lucidum

Nitric oxide (NO) is an important signalling molecule in stress response of organisms. We previously reported that NO decreases heat stress (HS)-induced ganoderic acid (GA) accumulation in Ganoderma lucidum. To explore the mechanisms by which NO modulates GA biosynthesis under HS, the effect of NO on the reactive oxygen species (ROS) content was examined. The results showed that NO decreased the production of mitochondrial ROS (mitROS) by 60% under HS. Further research revealed that NO reduced the mitROS content by inhibiting aconitase (Acon) activity. The GA content in Acon-silenced (Aconi) strains treated with NO donor did not differ significantly from that in untreated Aconi strains. To study the mechanism by which Acon activity is inhibited, the S-nitrosylation level of Acon was determined. Biotin-switch technology and mass spectrometry analysis were used to show that Acon is S-nitrosylated at the Cys-594 amino acid residue. Substitution of Cys-594 with a Ser, which cannot be S-nitrosylated, abolished the responsiveness of Acon to the NO-induced reduction in its enzymatic activity. These findings demonstrate that NO inhibits Acon activity through S-nitrosylation at Cys-594. In summary, these findings describe mechanism by which NO regulates GA biosynthesis via S-nitrosylation of Acon under HS condition in G. lucidum.