SEARCH · Engineering Papers

Results for “C”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,639 records · Page 91

All sources NASA NTRS DOE OSTI

DOE OSTI2024

Measurement of C P Violation Observables in D + → K − K + π + Decays

A search for violation of the charge-parity ( C P ) symmetry in the D + → K − K + π + decay is presented, with proton-proton collision data corresponding to an integrated luminosity of 5.4 fb − 1 , collected at a center-of-mass energy of 13 TeV with the LHCb detector. A novel model-independent technique is used to compare the D + and D − phase-space distributions, with instrumental asymmetries subtracted using the D s + → K − K + π + decay as a control channel. The p value for the hypothesis of C P conservation is 8.1%. The C P asymmetry observables A C P | S ϕ π + = ( 0.95 ± 0.4 3 stat ± 0.2 6 syst ) × 10 − 3 and A C P | S K ¯ * 0 K + = ( − 0.26 ± 0.5 6 stat ± 0.1 8 syst ) × 10 − 3 are also measured. These results show no evidence of C P violation and represent the most sensitive search performed through the phase space of a multibody decay. © 2024 CERN, for the LHCb Collaboration 2024 CERN

Aaij, R. (ORCID:0000000305331952)↗

DOE OSTI2025

First Determination of the Spin-Parity of Ξ c ( 3055 ) + , 0 Baryons

The Ξ b 0 ( − ) → Ξ c ( 3055 ) + ( 0 ) ( → D + ( 0 ) Λ ) π − decay chains are observed, and the spin-parity of Ξ c ( 3055 ) + ( 0 ) baryons is determined for the first time. The measurement is performed using proton-proton collision data at a center-of-mass energy of s = 13 TeV , corresponding to an integrated luminosity of 5.4 fb − 1 , recorded by the LHCb experiment between 2016 and 2018. The spin-parity of the Ξ c ( 3055 ) + ( 0 ) baryons is determined to be 3 / 2 + with a significance of more than 6.5 σ ( 3.5 σ ) compared to all other tested hypotheses. The up-down asymmetries of the Ξ b 0 ( − ) → Ξ c ( 3055 ) + ( 0 ) π − transitions are measured to be − 0.92 ± 0.10 ± 0.05 ( − 0.92 ± 0.16 ± 0.22 ), consistent with maximal parity violation, where the first uncertainty is statistical and the second is systematic. These results support the hypothesis that the Ξ c ( 3055 ) + ( 0 ) baryons correspond to the first D -wave λ -mode excitation of the Ξ c flavor triplet. © 2025 CERN, for the LHCb Collaboration 2025 CERN

Aaij, R.↗

DOE OSTI2018

The path from litter to soil: Insights into soil C cycling from long-term input manipulation and high-resolution mass spectrometry

The pathways carbon (C) takes from plant litter to soil organic matter (SOM) underlies our understanding of how soil C stocks and microbial decomposition will respond to climate change, and determining whether natural soil C sinks can be enhanced to offset potential losses. Long-term ecosystem-scale litter manipulations and innovations in the molecular characterization of SOM provide a unique opportunity to explore these dynamics. We incubated soils from a 20-year litter-input experiment for 525 days and asked how litter quantity and source (i.e., roots versus aboveground litter) affected soil C cycling, including microbial function and the size and molecular composition of C pools defined by degree of mineral association. Input exclusion led to a 30% loss of soil C, attributable largely to the non-mineral-associated C fraction, and was accompanied by declines in soil C decomposition. The absence of roots led to a shift in the microbial catabolic profile, though there was no evidence that root litter was preferentially stabilized. Carbon did not accumulate under litter addition. However, direct examination of the finest mineral fraction with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) revealed dramatic changes to the chemical composition of carbon. In particular, lipid content increased proportionally with input addition, and was subsequently mineralized during incubation, indicating that this apparently stable fraction is metabolically active. Moreover, non-metric dimensional scaling (NMS) showed that both litter treatments and incubation caused the molecular composition of SOM to diverge, and explained 79% of the variance in soil respiration. We conclude that the path from litter to soil is more complex than previously thought and mineral-associated SOM thought to be stable may be microbially available.

Reynolds, L L.↗

DOE OSTI2014

Gas-Phase Synthesis of the Benzyl Radical (C 6 H 5 CH 2 )

Dicarbon ($C_2$), the simplest bare carbon molecule, is ubiquitous in the interstellar medium and in combustion flames. A gas-phase synthesis is presented of the benzyl radical ($C_6H_5CH_2$) by the crossed molecular beam reaction of dicarbon, $C_2(X^1Σ_g^+, a^3Π_u$), with 2-methyl-1,3-butadiene (isoprene; $C_5H_8$; X 1 A') accessing the triplet and singlet $C_7H_8$ potential energy surfaces (PESs) under single collision conditions. The experimental data combined with ab initio and statistical calculations reveal the underlying reaction mechanism and chemical dynamics. On the singlet and triplet surfaces, the reactions involve indirect scattering dynamics and are initiated by the barrierless addition of dicarbon to the carbon–carbon double bond of the 2-methyl-1,3-butadiene molecule. These initial addition complexes rearrange via multiple isomerization steps, leading eventually to the formation of $C_7H_7$ radical species through atomic hydrogen elimination. The benzyl radical ($C_6H_5CH_2$), the thermodynamically most stable $C_7H_7$ isomer, is determined as the major product.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2023

Rational Design and Reticulation of Infinite qbe Rod Secondary Building Units into Metal–Organic Frameworks through a Global Desymmetrization Approach for Inverse C 3 H 8 /C 3 H 6 Separation

Abstract The development of reticular chemistry has enabled the construction of a large array of metal–organic frameworks (MOFs) with diverse net topologies and functions. However, dominating this class of materials are those built from discrete/finite secondary building units (SBUs), yet the designed synthesis of frameworks involving infinite rod‐shaped SBUs remain underdeveloped. Here, by virtue of a global linker desymmetrization approach, we successfully targeted a novel Cu‐MOF (Cu‐ASY) incorporating infinite Cu‐carboxylate rod SBUs with its structure determined by micro electron diffraction (MicroED) crystallography. Interestingly, the rod SBU can be simplified as a unique cylindric sphere packingqbetubule made of [4 3 .6 2 ] tiles, which further connect the tritopic linkers to give a newly discovered 3,5‐connectedgfcnet. Cu‐ASY is a permanent ultramicroporous material featuring 1D channels with highly inert surfaces and shows a preferential adsorption of propane (C 3 H 8 ) over propene (C 3 H 6 ). The efficiency of C 3 H 8 selective Cu‐ASY is validated by multicycle breakthrough experiments, giving C 3 H 6 productivity of 2.2 L/kg. Density functional theory (DFT) calculations reveal that C 3 H 8 molecules form multiple C−H⋅⋅⋅π and atypical C−H⋅⋅⋅ H−C van der Waals interactions with the inner nonpolar surfaces. This work therefore highlights the linker desymmetrization as an encouraging and intriguing strategy for achieving unique MOF structures and properties.

Chemistry↗

DOE OSTI2024

Graphitic Carbon Nitride Quantum Dots (g‐C 3 N 4 QDs): From Chemistry to Applications

Since their emergence in 2014, graphitic carbon nitride quantum dots (g-C 3 N 4 QDs) have attracted much interest from the scientific community due to their distinctive physicochemical features, including structural, morphological, electrochemical, and optoelectronic properties. Owing to their desirable characteristics, such as non-zero band gap, ability to be chemically functionalized or doped, possessing tunable properties, outstanding dispersibility in different media, and biocompatibility, g-C 3 N 4 QDs have shown promise for photocatalysis, energy devices, sensing, bioimaging, solar cells, optoelectronics, among other applications. As these fields are rapidly evolving, it is very strenuous to pinpoint the emerging challenges of the g-C 3 N 4 QDs development and application during the last decade, mainly due to the lack of critical reviews of the innovations in the g-C 3 N 4 QDs synthesis pathways and domains of application. Herein, an extensive survey is conducted on the g-C 3 N 4 QDs synthesis, characterization, and applications. Scenarios for the future development of g-C 3 N 4 QDs and their potential applications are highlighted and discussed in detail. In conclusion, the provided critical section suggests a myriad of opportunities for g-C 3 N 4 QDs, especially for their synthesis and functionalization, where a combination of eco-friendly/single step synthesis and chemical modification may be used to prepare g-C 3 N 4 QDs with, for example, enhanced photoluminescence and production yields.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2016

Comparison of [ 11 C]TZ1964B and [ 18 F]MNI659 for PET imaging brain PDE10A in nonhuman primates

Abstract Phosphodiesterase 10A ( PDE 10A) inhibitors show therapeutic effects for diseases with striatal pathology. PET radiotracers have been developed to quantify in vivo PDE 10A levels and target engagement for therapeutic interventions. The aim of this study was to compare two potent and selective PDE 10A radiotracers, [ 11 C] TZ 1964B and [ 18 F] MNI 659 in the nonhuman primate ( NHP ) brain. Double scans in the same cynomolgus monkey on the same day were performed after injection of [ 11 C] TZ 1964B and [ 18 F] MNI 659. Specific uptake was determined in two ways: nondisplaceable binding potential ( BP ND ) was calculated using cerebellum as the reference region and the PDE ‐10A enriched striatum as the target region of interest ( ROI ); the area under the time–activity curve ( AUC ) for the striatum to cerebellum ratio was also calculated. High‐performance liquid chromatography ( HPLC ) analysis of solvent‐extracted NHP plasma identified the percentage of intact tracer versus radiolabeled metabolites samples post injection of each radiotracer. Both radiotracers showed high specific accumulation in NHP striatum. [ 11 C] TZ 1964B has higher striatal retention and lower specific striatal uptake than [ 18 F] MNI 659. The BP ND estimates of [ 11 C] TZ 1964B were 3.72 by Logan Reference model (Logan REF ) and 4.39 by simplified reference tissue model ( SRTM ); the BP ND estimates for [ 18 F] MNI 659 were 5.08 (Logan REF ) and 5.33 ( SRTM ). AUC ratios were 5.87 for [ 11 C] TZ 1964B and 7.60 for [ 18 F] MNI 659. Based on BP ND values in NHP striatum, coefficients of variation were ~10% for [ 11 C] TZ 1964B and ~30% for [ 18 F] MNI 659. Moreover, the metabolism study showed the percentage of parent compounds were ~70% for [ 11 C] TZ 1964B and ~50% for [ 18 F] MNI 659 60 min post injection. These data indicate that either [ 11 C] TZ 1964B or [ 18 F] MNI 659 could serve as suitable PDE 10A PET radiotracers with distinguishing features for particular clinical application.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Photodepositing CdS on the Active Cyano Groups Decorated g‐C 3 N 4 in Z‐Scheme Manner Promotes Visible‐Light‐Driven Hydrogen Evolution

Abstract g‐C 3 N 4 /CdS heterojunctions are potential photocatalysts for hydrogen production but their traditional type‐II configuration generally leads to weak oxidative and reductive activity. How to construct the novel Z‐scheme g‐C 3 N 4 /CdS counterparts to address this issue remains a great challenge in this field. In this work, a new direct Z‐scheme heterojunction of defective g‐C 3 N 4 /CdS is designed by introducing cyano groups (NC‐) as the active bridge sites. Experimental observations in combination with density functional theory (DFT) calculations reveal that the unique electron‐withdrawing feature of cyano groups in the defective g‐C 3 N 4 /CdS heterostructure can endow this photocatalyst with numerous advantageous properties including high light absorption ability, strong redox performance, satisfactory charge separation efficiency, and long lifetime of charge carriers. Consequently, the resultant photocatalytic system exhibits more active performance than CdS and g‐C 3 N 4 under visible light and reaches an excellent hydrogen evolution rate of 1809.07 µmol h −1 g −1 , which is 6.09 times higher than pristine g‐C 3 N 4 . Moreover, the defective g‐C 3 N 4 /CdS photocatalyst maintains good stability after 40 h continuous test. This work provides new insights into design and construction of Z‐scheme heterojunctions for regulating the visible‐light‐induced photocatalytic activity for H 2 evolution.

Wang, Zhipeng↗

DOE OSTI2022

Exploring Material Solutions for Supercritical CO 2 Applications above 800 °C

There has been recent interest in exploring revolutionary supercritical CO 2 (sCO 2 ) power cycles, and this exploratory investigation was seeking materials with CO 2 compatibility at up to 1200 °C. Here, initial exposures were conducted at 0.1 and 2 MPa CO 2 for up to 1000 h at 900–1200 °C. As expected, specimens of Mo and W that might be used as matrix materials in cermets were rapidly attacked under these conditions. Even an alumina-forming FeCrAlMo alloy showed high mass gains in less than 100 h at 1200 °C due to the formation of Fe-rich oxide. However, at 900–1100 °C, more protective behavior was observed for FeCrAlMo specimens, with or without pre-oxidation, in 0.1 MPa CO 2 , but increased attack was observed in 2 MPa CO 2 . In contrast, most Ni-based alloys exposed at 900–1100 °C showed higher mass gains and thicker reaction products than formed in air. Thus, Ni-based alloys appear less compatible with CO 2 environments above 800 °C compared to lower temperatures. Low mass gains were observed for CVD SiC at 900–1200 °C, but MoSi 2 and Mo(Si,Al) 2 specimens did not form protective scales under these conditions at 1000 and 1100 °C.

36 MATERIALS SCIENCE↗

DOE OSTI2019

Co-adsorption of O{sub 2} and C{sub 2}H{sub 4} on a Free Gold Dimer Probed via Infrared Photodissociation Spectroscopy

Infrared multiple photon dissociation (IR-MPD) spectroscopy in conjunction with density functional theory (DFT) calculations has been employed to study the activation of molecular oxygen and ethylene co-adsorbed on a free gold dimer cation Au{sub 2}{sup +}. Both studied complexes, Au{sub 2}O{sub 2}(C{sub 2}H{sub 4}){sup +} and Au{sub 2}O{sub 2}(C{sub 2}H{sub 4}){sub 2}{sup +}, show distinct features of both intact O{sub 2} and ethylene co-adsorbed on the cluster. However, the ethylene C=C double bond is activated, increasing in length by up to 0.07 Å compared with the free molecule, and the red shift of the O–O vibration frequency increases with the number of adsorbed ethylene molecules, indicating a small but increasing activation of the O–O bond. The small O{sub 2} activation and the rather weak interaction between O{sub 2} and C{sub 2}H{sub 4} are also reflected in the calculated electronic structure of the co-adsorption complexes which shows only a small occupation of the empty anti-bonding O{sub 2} 2π{sup *}{sub 2p} orbital as well as the localization of most of the Kohn–Sham orbitals on O{sub 2} and C{sub 2}H{sub 4}, respectively, with only limited mixing between O{sub 2} and C{sub 2}H{sub 4} orbitals. The results are compared with theoretical studies on neutral Au{sub x}O{sub 2}(C{sub 2}H{sub 4}) (x = 3, 5, 7, 9) complexes. .

74 ATOMIC AND MOLECULAR PHYSICS↗

DOE OSTI2013

C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells

Highlights: •The c-Myc oncogene directly upregulates miR-26a expression in GBM cells. •ChIP assays demonstrate that c-Myc interacts with the miR-26a promoter. •Luciferase reporter assays show that PTEN is a specific target of miR-26a. •C-Myc–miR-26a suppression of PTEN may regulate the PTEN/AKT pathway. •Overexpression of c-Myc enhances the proliferative capacity of GBM cells. -- Abstract: The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

The p-ERK–p-c-Jun–cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract

Highlights: • Smooth muscle cells proliferated after exposure to cigarette smoke extract. • The p-ERK, p-c-Jun, and cyclinD1 expressions increased in the process. • The p-ERK inhibitor, U0126, can reverse these effects. • The p-ERK → p-c-Jun → cyclinD1 pathway is involved in the process. - Abstract: An epidemiological survey has shown that smoking is closely related to atherosclerosis, in which excessive proliferation of vascular smooth muscle cells (SMCs) plays a key role. To investigate the mechanism underlying this unusual smoking-induced proliferation, cigarette smoke extract (CSE), prepared as smoke-bubbled phosphate-buffered saline (PBS), was used to induce effects mimicking those exerted by smoking on SMCs. As assessed by Cell Counting Kit-8 detection (an improved MTT assay), SMC viability increased significantly after exposure to CSE. Western blot analysis demonstrated that p-ERK, p-c-Jun, and cyclinD1 expression increased. When p-ERK was inhibited using U0126 (inhibitor of p-ERK), cell viability decreased and the expression of p-c-Jun and cyclinD1 was reduced accordingly, suggesting that p-ERK functions upstream of p-c-Jun and cyclinD1. When a c-Jun over-expression plasmid was transfected into SMCs, the level of cyclinD1 in these cells increased. Moreover, when c-Jun was knocked down by siRNA, cyclinD1 levels decreased. In conclusion, our findings indicate that the p-ERK–p-c-Jun–cyclinD1 pathway is involved in the excessive proliferation of SMCs exposed to CSE.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Investigation of the redox-dependent modulation of structure and dynamics in human cytochrome c

Redox-dependent changes in the structure and dynamics of human cytochrome c (Cyt c) were investigated by solution NMR. We found significant structural changes in several regions, including residues 23–28 (loop 3), which were further corroborated by chemical shift differences between the reduced and oxidized states of Cyt c. These differences are essential for discriminating redox states in Cyt c by cytochrome c oxidase (CcO) during electron transfer reactions. Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments identified that the region around His33 undergoes conformational exchanges on the μs-ms timescale, indicating significant redox-dependent structural changes. Because His33 is not part of the interaction site for CcO, our data suggest that the dynamic properties of the region, which is far from the interaction site for CcO, contribute to conformational changes during electron transfer to CcO. - Highlights: • Solution structure and dynamics analysis for human Cyt c by NMR. • Structural changes responsible for the discrimination of the redox state in Cyt c. • Conformational exchange in the region outside of the interaction site for CcO. • Less flexibility and rigid structure of the interaction site on Cyt c for CcO.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2016

Functional interaction between nonreceptor tyrosine kinase c-Abl and SR-Rich protein RBM39

RBM39, also known as splicing factor HCC1.4, acts as a transcriptional coactivator for the steroid nuclear receptors JUN/AP-1, ESR1/ER-α and ESR2/ER-β. RBM39 is involved in the regulation of the transcriptional responses of these steroid nuclear receptors and promotes transcriptional initiation. In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner. The results suggest that mammalian c-Abl plays an important role in steroid hormone receptor-mediated transcription by regulating RBM39. - Highlights: • c-Abl interacts with RBM39. • RBM39 is phosphorylated by c-Abl. • c-Abl regulates transcriptional coactivation activity of RBM39 on the ERα and PRβ.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

C-terminal tail of NADPH oxidase organizer 1 (Noxo1) mediates interaction with NADPH oxidase activator (Noxa1) in the NOX1 complex

NOX1 (NADPH oxidase) similar to phagocyte NADPH oxidase, is expressed mainly in the colon epithelium and it is responsible for host defense against microbial infections by generating ROS (reactive oxygen species). NOX1 is activated by two regulatory cytosolic proteins that form a hetero-dimer, Noxo1 (NOX organizer 1) and Noxa1 (NOX activator 1). The interaction between Noxa1 and Noxo1 is critical for activating NOX1. However no structural studies for interaction between Noxa1 and Noxo1 has not been reported till date. Here, we studied the inter-molecular interaction between the SH3 domain of Noxa1 and Noxo1 using pull-down assay and NMR spectroscopy. {sup 15}N/{sup 13}C-labeled SH3 domain of Noxa1 has been purified for hetero-nuclear NMR experiments (HNCACB, CBCACONH, HNCA, HNCO, and HSQC). TALOS analysis using backbone assignment data of the Noxa1 SH3 domain showed that the structure primarily consists of β-sheets. Data from pull-down assay between the Noxo1 and Noxa1 showed that the SH3 domains (Noxa1) is responsible for interaction with Noxo1 C-terminal tail harboring proline rich region (PRR). The concentration-dependent titration of the Noxo1 C-terminal tail to Noxa1 shows that Noxo1 particularly in the RT loop: Q407*, H408, S409, A412*, G414*, E416, D417, L418, and F420; n-Src loop: C430, E431*, V432*, A435, W436, and L437; and terminal region: I447; F448*, F452* and V454 interact with Noxa1. Our results will provide a detailed understanding for interaction between Noxa1 and Noxo1 at the molecular level, providing insights into their cytoplasmic activity-mediated functioning as well as regulatory role of C-terminal tail of Noxo1 in the NOX1 complex. - Highlights: • C-terminal of Noxo1 harboring PRR motif is important for Noxa1 interaction. • Noxa1 SH3 binds C-terminal region of Noxo1with K{sub d} of 8.2 ± 1.41 μM. • Data from NMR experiments determined secondary structures of Noxa1 SH3. • Noxa1 interacts with PRR region of Noxo1, however, binding affinity is weaker than C-terminal tail of Noxo1. • Our results provide insights into regulatory role of C-terminal tail of Noxo1 in the NOX1 complex.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Enhancement of TGF-β-induced Smad3 activity by c-Abl-mediated tyrosine phosphorylation of its coactivator SKI-interacting protein (SKIP)

c-Abl is a non-receptor-type tyrosine kinase that plays an important role in cell proliferation, migration, apoptosis, and fibrosis. Furthermore, although c-Abl is involved in transforming growth factor-β (TGF-β) signaling, its molecular functions in TGF-β signaling are not fully understood. Here, we found that c-Abl phosphorylates SKI-interacting protein (SKIP), a nuclear cofactor of the transcription factor Smad3. The c-Abl inhibitor imatinib suppressed TGF-β-induced expression of Smad3 targets as well as SKIP/Smad3 interaction. TGF-β-stimulation induced tyrosine phosphorylation of SKIP, and this phosphorylation was suppressed by imatinib. Tyr{sup 292}, Tyr{sup 430}, and Tyr{sup 433} residues in SKIP were shown to be involved in c-Abl-mediated phosphorylation. Phosphomimetic glutamic acid substitution at Tyr{sup 292} in SKIP enhanced, whereas its phospho-dead phenylalanine substitution attenuated TGF-β-induced SKIP/Smad3 interaction. Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3. Taken together, these results suggest that c-Abl phosphorylates SKIP mainly at Tyr{sup 292} and promotes SKIP/Smad3 interaction for the full activation of TGF-β/Smad3 signaling. - Highlights: • c-Abl promotes TGF-β-induced SKIP/Smad3 interaction. • c-Abl phosphorylates SKIP upon TGF-β stimulation. • Phosphorylation of SKIP at Tyr{sup 292} enhances SKIP/Smad3 binding and Smad3 activity.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell

Current therapies available for the treatment of human osteosarcoma, an aggressive bone tumor, are insufficient. To examine an alternative approach of integrin-based anti-osteosacoma strategy, acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin, was isolated and evaluated for its application in combination with two potent inhibitors of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8). The investigation of human osteosarcoma MG-63 cells pre-incubated with a FGF receptor-1 (FGFR-1) blocker AZD4547, a CXC-chemokine receptor-1/-2 (CXCR1/2) antagonist reparixin, and acurhagin-C via two given modes of separation and combination was executed. Detected by flow cytometry, integrins-α2/-α5/-αv/-β1, FGFR-1, CXCR1 and CXCR2 constitutively express on the resting membrane. However, bFGF/IL-8-activated MG-63 cells only statistically enhanced the surface exposure of integrins-α5/-β1, FGFR-1 and CXCR2. In activated MG-63 cells, acurhagin-C targeting integrin-α5 not only might potentiate the inhibitory effect of AZD4547 and reparixin on the surface expression of integrin-α5, FGFR-1 and CXCR2, but also acurhagin-C used alone remained effectively to diminish the surface exposure of those targeted receptors. Hence, a complicated crosstalk mechanism should be involved in the membrane interactions. Furthermore, co-administration of acurhagin-C with AZD4547 and reparixin also showed to have the synergistic suppression toward cell proliferation and the gene expression of matrix metalloproteinase-2. Also, the administration of three-in-one mode could nearly abrogate the cellular attachment onto collagen-IV- and fibronectin-coated wells, as well as penetration into Matrigel-barrier. These data supported an ECD-disintegrin acurhagin-C targeting integrin-α5 upon combined used with AZD4547 and reparixin may become a promising therapeutic approach for attenuating osteosarcoma development. - Highlights: • Acurhagin-C against integrins exerts the application in anti-osteosacoma therapy. • Acurhagin-C in combination with AZD4547 and reparixin has synergistic inhibitions. • The 3 in 1 treatment can diminish MG-63 cells proliferation and MMP-2 expression. • The 3 in 1 treatment can effectively disturb MG-63 cells adhesion and invasion.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Overexpressing circular RNA hsa{sub c}irc{sub 0}002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, whose importance in cancer has been gradually acknowledged. However, the functions of circRNAs in tumorigenesis have not been fully understood. In the present study, we identified a novel circRNA hsa{sub c}irc{sub 0}002052 significantly downregulated in osteosarcoma (OS) tissues and cell lines. Moreover, we found that hsa{sub c}irc{sub 0}002052 could act as a biomarker to indicate the prognosis of OS patients. Functionally, we showed that hsa{sub c}irc{sub 0}002052 overexpression significantly suppressed OS cell proliferation, migration and invasion while promoting apoptosis in vitro. Similarly, in vivo assay indicated that ectopic expression of hsa{sub c}irc{sub 0}002052 impaired OS cell growth. In terms of mechanism, we found that hsa{sub c}irc{sub 0}002052 inhibited miR-1205 while miR1205 targeted APC2, a negative regulator of Wnt/β-catenin signaling pathway. By releasing the inhibition of miR-1205 on APC2 expression, hsa{sub c}irc{sub 0}002052 suppressed the activation of Wnt/β-catenin signaling pathway, leading to attenuated OS progression. Taken together, our study for the first time revealed a suppressive circRNA hsa{sub c}irc{sub 0}002052 involved in OS progression. Our study suggested hsa{sub c}irc{sub 0}002052/miR-1205/APC2/Wnt/β-catenin axis might be a potential target for OS therapy.

60 APPLIED LIFE SCIENCES↗