The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients. We found that GAS7 was associated with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis via blocking CYFIP1 and Rac1 protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. We further demonstrated that p53 directly regulated GAS7 gene expression, which was inversely correlated with p53 mutations in breast cancer specimens. Our study uncover a novel regulatory mechanism of p53 in early onset breast cancer progression through GAS7–CYFIP1-mediated signaling pathways.
A self-assembled spongy-like (S) ultralight (ρ ≈ 140 mg cm −3 ) aerogel was fabricated through polypyrrole (PPy) and reduced graphene oxide (RGO). Firstly, the dispersed graphene oxide (GO) were locked homogeneously in those chains formed by the gelation of PPy. Then a hydrothermal process was employed to reduce GO to RGO. With a trace content of RGO (0.43 wt% in aerogel), the electromagnetic absorption (EA) performance had been significant improved. Only with a very low filler loading (10 wt%), the S-PPy/RGO aerogel based composite could reach an effective EA bandwidth (below − 10 dB) of 6.76 GHz, and the highest reflection coefficient reached − 54.4 dB at 12.76 GHz. It was demonstrated that this aerogel material can be considered as an effective route to design a light weight and high performance EA material. Furthermore, the 3D-PPy/RGO aerogel also showed a suitable pollution treatment performance with different solvents and dyes. materials, such as intercalated graphite, 14 carbon nanotubes (CNTs), 15,16 porous carbon, 17,18 carbon nanopowders, 19 carbon fibers, 20 graphene, 21 and reduced graphene oxide (RGO). 22 Benefit from the nano-structure, these above mentioned materials can reach an ideal EA performance with a fitting filler loading ratio in composites. However, metal oxide or sulfide based EA composites can't overcome high filler loading ratio, even reach 70.0 wt%; 5 pure carbon materials based EA composites can't get a sufficient broad effective EA bandwidth (below − 10 dB) with low matching thickness, though they give low loading ratio in composites (less than 20.0 wt%).Taking RGO for instance, it is a kind of two dimensional (2D) carbon material that can be synthesized from graphene oxide (GO) using chemical, 23 thermal, 24 optical, 25,26 and hydrothermal 27 methods. Dielectric loss and the low density of RGO enable it to be used as EA material. With a suitable preparation process, pure RGO based composite can display an effective EA bandwidth of 4.32 GHz with a thickness of 4 mm. 22 The development of functional RGO modified with other nanoparticles also represents an important advance to improve EA performance both in width and intensity, meanwhile reduce the thickness of the composites, such as Fe Furthermore, core-shell structures, for example, Fe 3 O 4 @ZnO, 44 SiO 2 @Fe 3 O 4 , 45 and Fe 3 O 4 @Fe, 46 can also improve the EA performance of RGO.Besides the above mentioned EA materials, recently, the intrinsically conducting polymers (ICPs) with low densities, such as PEDOT, PANi and polypyrrole (PPy), are also great interest as EA materials and EA performance are closely related to the structure. 46 However, composite only loaded with single ICP is not enough to produce sufficient electric loss, which limits its application in broadband absorber. Although the EA performance can be improved through hybridizing other semiconductors or RGO is only trace content (0.43 wt%) in aerogel to match the impedance with air, which makes this aerogel cheap enough for large-scaled use. Furthermore, the S-PP...
The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance.
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