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.

No abstract

The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR-128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of fibrosis, and attenuating cardiac dysfunction in response to MI. These results suggest that miR-128 serves as a critical regulator of endogenous CM proliferation, and might be a novel therapeutic target for heart repair.

BackgroundOvarian cancer (OCa) peritoneal metastasis is the leading cause of cancer–related deaths in women with limited therapeutic options available for treating it and poor prognosis, as the underlying mechanism is not fully understood.MethodThe clinicopathological correlation of G9a expression was assessed in tumor specimens of ovarian cancer patients. Knockdown or overexpression of G9a in ovarian cancer cell lines was analysed with regard to its effect on adhesion, migration, invasion and anoikis-resistance. In vivo biological functions of G9a were tested by i.p. xenograft ovarian cancer models. Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream target genes.ResultsWe found that the expression of histone methyltransferase G9a was highly correlated with late stage, high grade, and serous-type OCa. Higher G9a expression predicted a shorter survival in ovarian cancer patients. Furthermore, G9a expression was higher in metastatic lesions compared with their corresponding ovarian primary tumors. Knockdown of G9a expression suppressed prometastatic cellular activities including adhesion, migration, invasion and anoikis-resistance of ovarian cancer cell lines, while G9a over-expression promoted these cellular properties. G9a depletion significantly attenuated the development of ascites and tumor nodules in a peritoneal dissemination model. Importantly, microarray and quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer. Expression of these genes was also inversely correlated with G9a expression in OCa specimens.ConclusionWe propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-189) contains supplementary material, which is available to authorized users.

Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C=C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C=C isomer compositions associated with diseases, while the biochemistry has not been fully understood due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy, MELDI (mCPBA Epoxidation for Lipid Double-bond Identification), which enables both large-scale identification and spatial mapping of biological C=C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among mono-and poly-unsaturated fatty acids and glycerophospholipids in both human serum, where novel isomers of low abundance were unambiguously quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate underlying lipid biochemistry.

The geometric stability, electronic structure and catalytic properties of a single Pd atom deposited on a pristine MoCO monolayer and a defective MoCO monolayer with an oxygen vacancy (denoted as Pd/O-MoCO) are systematically investigated through density functional theory. We find that the oxygen vacancy (O) can stabilize the single Pd atom and make the Pd/O-MoCO system an excellent mono-dispersed atomic catalyst. The Pd dopant serves as an active center which makes the intermediates react productively around it. Three reaction mechanisms are considered for CO oxidation to test the catalytic activity of Pd/O-MoCO, which exhibits high activity for CO oxidation via a tri-molecular Eley-Rideal (TER) mechanism with a rate-limiting energy barrier of 0.49 eV. The pre-adsorbed CO molecules on the Pd dopant could transfer electrons to the O-2π* orbitals, which would promote O molecule activation and induce O-O bond scission. This work demonstrates that the defective monolayer MXene may serve as a promising sort of support to fabricate single atomic catalysts (SACs) for CO oxidation or other reactions, agreeing well with the experimental reports, which opens up a new avenue for the design and fabrication of SACs of MXene-based materials.