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Pathway analysis allows us to gain insights into a comprehensive understanding of the molecular mechanisms underlying cancers. Currently, high-throughput multi-omics data and various types of large-scale biological networks enable us to identify cancer-related pathways by comprehensively analyzing these data. Combining information from multidimensional data, pathway databases and interaction networks is a promising strategy to identify cancer-related pathways. Here we present a novel network-based approach for integrative analysis of DNA methylation and gene expression data to extend original pathways. The results show that the extension of original pathways can provide a basis for discovering new components of the original pathway and understanding the crosstalk between pathways in a large-scale biological network. By inputting the gene lists of the extended pathways into the classical gene set analysis (ORA and FCS), we effectively identified the altered pathways which are correlated well with the corresponding cancer. The method is evaluated on three datasets retrieved from TCGA (BRCA, LUAD and COAD). The results show that the integration of DNA methylation and gene expression data through a network of known gene interactions is effective in identifying altered pathways.

A multidisciplinary approach was used to investigate the causes of the distributions and sinking rates of transparent exopolymer particles (TEPs) during the period of September–October (2017) in the Western Pacific Ocean (WPO); the study period was closely dated to a northwest typhoon surge. The present study discussed the impact of biogeophysical features on TEPs and their sinking rates (sTEP) at depths of 0–150 m. During the study, the concentration of TEPs was found to be higher in areas adjacent to the Kuroshio current and in the bottom water layer of the Mindanao upwelling zone due to the widespread distribution of cyanobacteria, i.e., Trichodesmium hildebrandti and T. theibauti. The positive significant regressions of TEP concentrations with Chl-a contents in eddy-driven areas (R2 = 0.73, especially at 100 m (R2 = 0.75)) support this hypothesis. However, low TEP concentrations and TEPs were observed at mixed layer depths (MLDs) in the upwelling zone (Mindanao). Conversely, high TEP concentrations and high sTEP were found at the bottom of the downwelling zone (Halmahera). The geophysical directions of eddies may have caused these conditions. In demonstrating these relations, the average interpretation showed the negative linearity of TEP concentrations with TEPs (R2 = 0.41 ~ 0.65) at such eddies. Additionally, regression curves (R2 = 0.78) indicated that atmospheric pressure played a key role in the changes in TEPs throughout the study area. Diatoms and cyanobacteria also curved the TEPs significantly (R2 = 0.5, P

Biomass gasification, especially distribution to power generation, is considered as a promising way to tackle global energy and environmental challenges. However, previous researches on integrated analysis of the greenhouse gases (GHG) abatement potentials associated with biomass electrification are sparse and few have taken the freshwater utilization into account within a coherent framework, though both energy and water scarcity are lying in the central concerns in China's environmental policy. This study employs a Life cycle assessment (LCA) model to analyse the actual performance combined with water footprint (WF) assessment methods. The inextricable trade-offs between three representative energy-producing technologies are explored based on three categories of non-food crops (maize, sorghum and hybrid pennisetum) cultivated in marginal arable land. WF results demonstrate that the Hybrid pennisetum system has the largest impact on the water resources whereas the other two technology options exhibit the characteristics of environmental sustainability. The large variances in contribution ratio between the four sub-processes in terms of total impacts are reflected by the LCA results. The Anaerobic Digestion process is found to be the main contributor whereas the Digestate management process is shown to be able to effectively mitigate the negative environmental impacts with an absolute share. Sensitivity analysis is implemented to detect the impacts of loss ratios variation, as silage mass and methane, on final results. The methane loss has the largest influence on the Hybrid pennisetum system, followed by the Maize system. Above all, the Sorghum system demonstrates the best performance amongst the considered assessment categories. Our study builds a pilot reference for further driving large-scale project of bioenergy production and conversion. The synergy of combined WF-LCA method allows us to conduct a comprehensive assessment and to provide insights into environmental and resource management.

Biomass gasification, especially distribution to power generation, is considered as a promising way to tackle global energy and environmental challenges. However, previous researches on integrated analysis of the greenhouse gases (GHG) abatement potentials associated with biomass electrification are sparse and few have taken the freshwater utilization into account within a coherent framework, though both energy and water scarcity are lying in the central concerns in China’s environmental policy. This study employs a Life cycle assessment (LCA) model to analyse the actual performance combined with water footprint (WF) assessment methods. The inextricable trade-offs between three representative energy-producing technologies are explored based on three categories of non-food crops (maize, sorghum and hybrid pennisetum) cultivated in marginal arable land. WF results demonstrate that the Hybrid pennisetum system has the largest impact on the water resources whereas the other two technology options exhibit the characteristics of environmental sustainability. The large variances in contribution ratio between the four sub-processes in terms of total impacts are reflected by the LCA results. The Anaerobic Digestion process is found to be the main contributor whereas the Digestate management process is shown to be able to effectively mitigate the negative environmental impacts with an absolute share. Sensitivity analysis is implemented to detect the impacts of loss ratios variation, as silage mass and methane, on final results. The methane loss has the largest influence on the Hybrid pennisetum system, followed by the Maize system. Above all, the Sorghum system demonstrates the best performance amongst the considered assessment categories. Our study builds a pilot reference for further driving large-scale project of bioenergy production and conversion. The synergy of combined WF-LCA method allows us to conduct a comprehensive assessment and to provide insights into environmental and resource management.

This paper describes a recent landslide event, which occurred at Liucheng village in Tianquan County, Sichuan Province, China, on July 15, 2018. The Laochang landslide described in this research is an outstanding and valuable reference for understanding the characteristics of such kind of landslides that are geologically similar to the landslide. The deformation characteristics of the landslide are investigated based on field investigations, drilled boreholes, and exploratory trenches. The 225 residents of 64 households living on the flat platform were threatened by the landslide. Therefore, to guarantee the safety of human life and property becomes the primary emergency task. The anti-sliding piles were taken to stabilize the landslide and mitigate impacts caused by the landslide. Based on the analysis of the monitoring data, the effectiveness of anti-sliding piles is evaluated. The results indicate that the anti-sliding piles are effective in increasing the stability of the landslide, and this work can provide a reference for similar slope engineering projects.

A facile one-step supramolecular assembly method is adopted to modify reduced graphene oxide (rGO) with functional organic molecule pyranine for achieving comprehensive humidity sensing performance. The fabricated humidity sensor based on pyranine modified-reduced graphene oxide (Pyr-rGO) exhibits excellent sensing performance with ultrafast (L/IH = 6000 as relative humidity (RH) consecutively changes between 11% and 95%; small hysteresis of 8% RH; reliable repeatability and stability. In addition, a detailed mechanism analysis is performed to investigate the difference in water adsorption and ions transfer under various RH levels. Notably, the one-step supramolecular assembly method to prepare Pyr-rGO provides a new insight into developing novel functional humidity sensing materials with enhanced device performance.

Epidermal growth factor receptor (EGFR) T790M acquired drug-resistance mutation has become a major clinical challenge for the therapy of non-small cell lung cancer. Here, we applied a structure-guided approach on the basis of the previous reported EGFR inhibitor (compound 9), and designed a series of C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives as novel mutant-selective EGFR inhibitors. Finally, the most representative compound 20a was identified, which showed high selectivity at both enzymatic and cellular levels against EGFRL858R/T790M (H1975 cell lines) over EGFRWT (A431 cell lines). The representative compound 20a also showed promising antitumor efficiency in the in vivo antitumor efficacy study of H1975 xenograft mouse model driven by EGFRL858R/T790M. These results provide a new scaffold for the treatment of dual-mutant-driven non-small cell lung cancer.

Boron nitride nanosheets (BNNS) hold the similar two-dimensional structure as graphene and unique properties complementary to graphene, which makes it attractive in application ranging from electronics to energy storage. The exfoliation of boron nitride (BN) still remains challenge and hinders the applications of BNNS. In this work, the preparation of BNNS has been realized by a shear-assisted supercritical CO2 exfoliation process, during which supercritical CO2 intercalates and diffuses between boron nitride layers, and then the exfoliation of BN layers is obtained in the rapid depressurization process by overcoming the van der Waals forces. Our results indicate that the bulk boron nitride has been successfully exfoliated into thin nanosheets with an average 6 layers. It is found that the produced BNNS is well-dispersed in isopropyl alcohol (IPA) with a higher extinction coefficient compared with the bulk BN. Moreover, the BNNS/epoxy composite used as thermal interface materials has been prepared. The introduction of BNNS results in a 313% enhancement in thermal conductivity. Our results demonstrate that BNNS produced by supercritical CO2 exfoliation show great potential applications for heat dissipation of high efficiency electronics.

Klf5, a member of the Krüppel-like transcription factor family, has essential roles during embryonic development, cell proliferation, differentiation, migration and apoptosis. This study was to define molecular mechanism of Klf5 during the odontoblastic differentiation. The expression of Klf5, odontoblast-differentiation markers, Dspp and Dmp1 was co-localized in odontoblastic cells at different stages of mouse tooth development and mouse dental papilla mesenchymal cells. Klf5 was able to promote odontoblastic differentiation and enhance mineral formation of mouse dental papilla mesenchymal cells. Furthermore, overexpression of Klf5 could up-regulate Dspp and Dmp1 gene expressions in mouse dental papilla mesenchymal cells. In silico analysis identified that several putative Klf5 binding sites in the promoter and first intron of Dmp1 and Dspp genes that are homologous across species lines. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Klf5 bound to these motifs in vitro and in intact cells. The responsible regions of Dmp1 gene were located in the promoter region while effect of Klf5 on Dspp activity was in the first intron of Dspp gene. Our results identify Klf5 as an activator of Dmp1 and Dspp gene transcriptions by different mechanisms and demonstrate that Klf5 plays a pivotal role in odontoblast differentiation.

We theoretically investigate light absorption by a graphene monolayer that is coated on the outside of dielectric-metal core-shell resonators (DMCSRs). We demonstrate that light absorption of graphene can be greatly enhanced in such multi-layered core-shell architectures as a result of the excitation of the hybridized bonding plasmon resonance supported by the DMCSRs. We also demonstrate that the absorption enhancement in graphene can be easily tuned over a wide range from the visible to the near-infrared, and particularly the enhancement factor can be optimally maximized at any selective wavelength, by simultaneously varying the dielectric core size and the metal shell thickness. Our results suggest that the graphene-wrapped DMCSRs with strong and highly wavelength-tunable absorption enhancement in graphene could be attractive candidates for applications in graphene-based photodetectors and image sensors.

Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1.

Crosslinking is an effective way to fabricate high-selective CO2 separation membranes because of its unique crosslinking framework. Thus, it is essentially significant to study the influence of crosslinking degree on the permeation selectivities of CO2. Herein, we report a successful and facile synthesis of a series of polyethylene oxide (PEO)-based diblock copolymers (BCP) incorporated with an unique UV-crosslinkable chalcone unit using Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) process. The membranes of as-prepared BCPs show superior carbon dioxide (CO2) separation properties as compared to nitrogen (N2) after UV-crosslinking. Importantly, the influence of different proportions of crosslinked chalcone on CO2 selectivities was systematically investigated, which revealed that CO2 selectivities increased obviously with the enhancement of chalcone fractions within a certain limit. Further, the CO2 selectivities of block copolymer with the best block proportion was studied by varying the crosslinking time which confirmed that the high crosslinking degree exhibited a better CO2/N2 (αCO2/N2) selectivities. A possible mechanism model revealing that the crosslinking degree played a key role in the gas separation process was also proposed.

Aspergillus flavus is a pathogenic fungus that produces toxic and carcinogenic aflatoxins and is the causative agent of aflatoxicosis. A growing body of evidence indicates that reversible phosphorylation plays important roles in regulating diverse functions in this pathogen. However, only a few phosphoproteins of this fungus have been identified, which hampers our understanding of the roles of phosphorylation in A. flavus. So we performed a global and site-specific phosphoproteomic analysis of A. flavus. A total of 598 high-confidence phosphorylation sites were identified in 283 phosphoproteins. The identified phosphoproteins were involved in various biological processes, including signal transduction and aflatoxins biosynthesis. Five identified phosphoproteins associated with MAPK signal transduction and aflatoxins biosynthesis were validated by immunoblotting using phospho-specific antibodies. Further functional studies revealed that phosphorylation of the MAP kinase kinase kinase Ste11 affected aflatoxins biosynthesis in A. flavus. Our data represent the results of the first global survey of protein phosphorylation in A. flavus and reveal previously unappreciated roles for phosphorylation in the regulation of aflatoxins production. The generated dataset can serve as an important resource for the functional analysis of protein phosphorylation in A. flavus and facilitate the elucidation of phosphorylated signaling networks in this pathogen.

N, N-diethyl-m-toluamide (DEET) is one of the important emerging contaminants that are being increasingly detected in reclaimed water as well as in drinking water sources. However, DEET is refractory to conventional biological treatment and pure ozone which is absent of hydroxyl radical. Current researches on the efficient removal of DEET are still quite limited. This study utilizes a novel method, namely ozone/graphene oxide (O3/GO), to investigate the effects on DEET removal in aqueous systems, especially in reclaimed water. The results indicate that the DEET degradation rate was significantly accelerated through the combined effect of GO and ozonation which can yield abundant hydroxyl radical, compared to pure ozone condition. According to hydroxyl radical scavenging experiments, hydroxyl radical was found to play a dominant role in synergistic removal of DEET. These findings can offer sound suggestions for future research on the removal of emerging organic contaminants. The information could also be beneficial to reclaimed water safety and sustainable management.

Plasmonic hot-electron generation has recently come into focus as a new scheme for solar energy conversion. So far, however, due to the relatively narrow bandwidth of the surface plasmon resonances and the insufficient resonant light absorption, most of plasmonic photocatalysts show narrow-band spectral responsivities and small solar energy conversion efficiencies. Here we experimentally demonstrate that a three-layered nanostructure, consisting of a monolayer gold-nanoparticles and a gold film separated by a TiO2 gap layer (Au-NPs/TiO2/Au-film), is capable of near-completely absorbing light within the whole visible region. We show that the Au-NPs/TiO2/Au-film device can take advantage of such strong and broadband light absorption to enhance the generation of hot electrons and thus the photocurrent under visible irradiation. As compared to conventional plasmonic photocatalysts such as Au-NPs/TiO2 nanostructures, a 5-fold-enhanced incident photon-to-current conversion efficiency is achieved within the entire wavelength range 450–850 nm in the Au-NPs/TiO2/Au-film device. Simulations show good agreements with the experimental results, demonstrating that only the plasmon-induced losses contribute to the enhanced photocurrent generation of the Au-NPs/TiO2/Au-film device.

We investigated the influence of gut microbiotal metabolism on the pharmacokinetics of berberine in healthy male Africans and Chinese. The Cmax and AUC in the Africans were 2.67-fold and 2.0-fold higher than the Chinese, respectively. Microbiotal compositions by 16S rRNA pyrosequencing showed higher abundance of the genera Prevotella, Bacteroides and Megamonas (34.22, 13.88 and 10.68%, respectively) in the Chinese than the Africans (30.08, 9.43 and 0.48%, respectively). Scatter plot showed a strong negative correlation between the microbiotal abundance and the berberine AUC, especially for the genus Prevotella (r = −0.813) and its species. A more extensive metabolism was observed in Chinese with 1.83-fold higher metabolites, possibly contributing to the lower AUC than the Africans. In conclusion, significant PK differences of berberine were observed between Africans and Chinese, which is partly attributable to variations in gut microbiota and its corresponding metabolic capacity.

The photo-reduction of metal ions in solution induced by femtosecond laser is an important and novel method for fabricating three-dimensional metal microstructures. However, the nonlinear absorption cross section of metal ions remains unknown because its measurement is difficult. In the present study, a method based on Two-Photon Excited Sedimentation (TPES) is proposed to measure the two-photon absorption cross section (TPACS) of metal ions in solution. The power-squared dependence of the amount of sediment on the excitation intensity was confirmed, revealing that 800 nm femtosecond laser induced reduction of metal ions was a two photon absorption process. We believe that the proposed method may be applied to measure the TPACS of several metal ions, thereby opening a new avenue towards future analysis of two-photon absorption materials.

ABO blood group system, a well-known genetic risk factor, has clinically been demonstrated to be linked with thrombotic vascular diseases. However, the relationship between ABO blood group and coronary artery disease (CAD) is still controversial. We here performed an updated meta-analysis of the related studies and tried to elucidate the potential role of ABO blood group as a risk factor for CAD. All detectable case-control and cohort studies comparing the risk of CAD in different ABO blood groups were collected for this analysis through searching PubMed, Embase and the Cochrane Library. Ultimately, 17 studies covering 225,810 participants were included. The combined results showed that the risk of CAD was significantly higher in blood group A (OR = 1.14, 95% CI = 1.03 to 1.26, p = 0.01) and lower in blood group O (OR = 0.85, 95% CI = 0.78 to 0.94, p = 0.0008). Even when studies merely about myocardial infarction (MI) were removed, the risk of CAD was still significantly higher in blood group A (OR = 1.05, 95% CI = 1.00 to 1.10, p = 0.03) and lower in blood group O (OR = 0.89, 95% CI = 0.85 to 0.93, p

Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life and further implying that ‘obesity’ might be an indicator of good health for cetaceans.

Efficient control of optical radiation at subwavelength scales plays important roles for various applications. Dielectric nanoparticles or dielectric shells with a large refractive index of n ~ 3–4, which are only achievable for limited semiconductors, are involved in most designs so far to control the scattering by overlapping the electric and magnetic dipolar modes of the same magnitude. Here we propose a new mechanism based on the interplay between dipolar and quadrupolar resonances of different amplitudes, both magnetic and electric, to suppress the backward scattering or the forward scattering by using metallo-dielectric core-shell nanoparticles with a dielectric shell layer having a refractive index of n = 2.0. We demonstrate that broadband zero-backward or near-zero-forward scattering can be achieved by optimizing the structural parameters. We also demonstrate that the core-shell nanoparticles with identical dielectric shells but metal cores with various sizes are able to suppress the backward or forward scattering at the same wavelength, thus revealing a large tolerance to fabrication errors induced by the size distributions in the metal cores. These features make the proposed core-shell nanoparticles beyond the dipole limit more easily realized in practical experiments.

Using nanomaterials to develop multimodal systems has generated cutting-edge biomedical functions. Herein, we develop a simple chemical-vapor-deposition method to fabricate graphene-isolated-Au-nanocrystal (GIAN) nanostructures. A thin layer of graphene is precisely deposited on the surfaces of gold nanocrystals to enable unique capabilities. First, as surface-enhanced-Raman-scattering substrates, GIANs quench background fluorescence and reduce photocarbonization or photobleaching of analytes. Second, GIANs can be used for multimodal cell imaging by both Raman scattering and near-infrared (NIR) two-photon luminescence. Third, GIANs provide a platform for loading anticancer drugs such as doxorubicin (DOX) for therapy. Finally, their NIR absorption properties give GIANs photothermal therapeutic capability in combination with chemotherapy. Controlled release of DOX molecules from GIANs is achieved through NIR heating, significantly reducing the possibility of side effects in chemotherapy. The GIANs have high surface areas and stable thin shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.

We have demonstrated the plasmonic characteristics of an ultrathin tetrahedral amorphous carbon (ta-C) film coated with Ag nanoparticles. The simulation result shows that, under resonant and non-resonant excitations, the strongest plasmonic electric field of 1 nm ta-C coated Ag nanoparticle is not trapped within the ta-C layer but is released to its outside surface, while leaving the weaker electric field inside ta-C layer. Moreover, this outside plasmonic field shows higher intensity than that of uncoated Ag nanoparticle, which is closely dependent on the excitation wavelength and size of Ag particles. These observations are supported by the SERS measurements. We expect that the ability for ultrathin ta-C coated Ag nanoparticles as the SERS substrates to detect low concentrations of target biomolecules opens the door to the applications where it can be used as a detection tool for integrated, on-chip devices.