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At least 793 records · Page 44

MAD2-p31comet axis deficiency reduces cell proliferation, migration and sensitivity of microtubule-interfering agents in glioma

Mitotic arrest deficient-like-1 (MAD2, also known as MAD2L1) is thought to be an important spindle assembly checkpoint protein, which ensures accurate chromosome segregation and is closely associated with poor prognosis in many cancer. As a MAD2 binding protein, p31{sup comet} counteracts the function of MAD2 and leads to mitotic checkpoint silence. In this study, we explore the function of MAD2-p31{sup comet} axis in malignant glioma cells. Our results showed that disruption of MAD2-p31{sup comet} axis by MAD2 knockdown or p31{sup comet} overexpression suppressed cell proliferation, survival and migration of glioma, indicating that MAD2-p31{sup comet} axis is required for maintaining glioma cells malignancy. It is noted that MAD2 depletion or p31{sup comet} overexpression reduced the sensitivity of glioma cells to microtubule-interfering agents paclitaxel and vinblastine, providing clinical guidance for application of such drugs. Taken together, our findings suggest that MAD2-p31{sup comet} axis may serve as a potential therapeutic target for glioma.

60 APPLIED LIFE SCIENCES↗

PUM1 promotes ovarian cancer proliferation, migration and invasion

Highlights: • This is the first investigation about PUM1 gene function in ovarian cancer. • PUM1 levels were significantly higher in ovarian cancer than in normal tissues. • PUM1 induces ovarian cancer cell growth, migration, and invasion in vitro. Abnormal expression of the PUM1 gene (pumilio RNA binding family member 1) is closely related to chromosomal mutations and carcinogenesis. However, there is no report about expression or function of PUM1 in ovarian cancer. The present study explored the role of PUM1 in the development and progression of ovarian cancer.

60 APPLIED LIFE SCIENCES↗

Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7

Highlights: • SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. • Low SPOP expression was a risk factor related to the prognosis of HCC patients. • SPOP inhibited HCC metastasis through interacting with SENP7 and promoting its degradation. Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients. Loss- and gain-of-function assays demonstrated that SPOP inhibited HCC cell migration and invasion in vitro. Mechanisitically, co-immunoprecipitation and ubiquitination assays revealed that SPOP recognized and bound SENP7 and promoted its degradation via ubiquitin-dependent proteolysis. Analysis of immunohistochemistry showed that vimentin expression was correlated negatively with SPOP and positively with SENP7. These results implied that increased degradation of SENP7 by overexpression of SPOP decreased vimentin levels, which in turn attenuated HCC cell metastasis. Moreover, in vivo assays showed that SPOP overexpression also significantly suppressed liver and lung metastases. In summary, SPOP inhibits HCC cell metastasis via ubiquitin-dependent SENP7 proteolysis and may thus serve as a new opinion for the prevention of HCC metastasis.

60 APPLIED LIFE SCIENCES↗

Circular RNA hsa{sub c}irc{sub 0}008039 promotes breast cancer cell proliferation and migration by regulating miR-432-5p/E2F3 axis

As the development of sequencing technology, more and more circular RNAs (circRNAs) are identified in human cancer tissues. Increasing evidences imply circRNAs are important regulators in tumor progression. Nevertheless, how circRNAs participate in breast cancer development and progression is not well understood. In the present study, we identified a novel circRNA hsa{sub c}irc{sub 0}008039 with upregulated expression level in breast cancer tissues. By functional experiments, we found that hsa{sub c}irc{sub 0}008039 depletion significantly suppressed the proliferation, arrested cell-cycle progression and reduced migration in breast cancer. Mechanistic investigations suggested that hsa{sub c}irc{sub 0}008039 served as a competing endogenous RNA (ceRNA) of miR-432-5p. Subsequently, E2F3 was identified as the functional target of miR-432-5p and overexpression of hsa{sub c}irc{sub 0}008039 elevated E2F3 expression in breast cancer. On the whole, our study indicated that hsa{sub c}irc{sub 0}008039 exerted oncogenic roles in breast cancer and suggested the hsa{sub c}irc{sub 0}008039/miR-432-5p/E2F3 axis might be a potential therapeutic target.

60 APPLIED LIFE SCIENCES↗

LRP4 promotes proliferation, migration, and invasion in papillary thyroid cancer

Dysregulation of cell proliferation and death is considered the foundation of the malignant biological characteristics of cancer. In this study, we conducted a comprehensive analysis of a massively parallel whole transcriptome resequencing of paired papillary thyroid cancer and normal thyroid tissues from 19 patients. In addition, we found that LRP4, a member of the low-density lipoprotein receptor-related protein family, is significantly overexpressed in thyroid carcinoma. We demonstrated through quantitative real-time polymerase chain reaction (qRT-PCR) that LRP4 is upregulated in papillary thyroid cancer (PTC) tissues. This observation was also consistent with data analyzed from The Cancer Genome Atlas (TCGA) cohort. Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target.

60 APPLIED LIFE SCIENCES↗

miR-125b-5p inhibits breast cancer cell proliferation, migration and invasion by targeting KIAA1522

Highlights: • miR-125b-5p expression was found downregulated in breast cancer. • We explored the tumor suppressive role of miR-125b-5p in breast cancer. • KIAA1522 was reported to function as oncogene in breast cancer. • KIAA1522 was a direct target of miR-125b-5p in breast cancer. Abnormal gene expression due to the dysregulation of microRNAs (miRNAs) often occurred in the initiation or progression of cancers. The aim of this present study was to investigate the function role of miR-125b-5p in breast cancer (BC). Expression levels of miR-125b-5p were determined by quantitative Real-time PCR. Biological functions of miR-125b-5p in the progression of BC were investigated with a series of in vitro experiments including cell counting kit-8 assay, colony formation assay, wound-healing assay and transwell invasion assay. The target of miR-125b-5p in BC was validated by luciferase activity reporter assay and western blot assay. We found miR-125b-5p expression was significantly reduced in BC cell lines compared to the normal breast epithelial cell line. Functional assays showed that cell proliferation, colony formation ability, cell migration, and cell invasion can be suppressed by miR-125b-5p overexpression. Besides, KIAA1522 was validated as a direct target of miR-125b-5p in BC. Collectively, our study showed that miR-125b-5p functions as a tumor suppressor and regulates BC progression through targeting KIAA1522.

60 APPLIED LIFE SCIENCES↗

MAL2 promotes proliferation, migration, and invasion through regulating epithelial-mesenchymal transition in breast cancer cell lines

Highlights: • We discovered that MAL2 is overexpressed in breast cancer cell lines. • Knocked down MAL2 could decrease the ability of proliferation, migration, and invasion of breast cancer cell lines. • MAL2 in breast cancer cell lines might act as an oncogene in breast cancer. • The abnormal expression of MAL2 can predict the progression of breast cancer and has significant biological implications. Breast cancer is one of the most common malignant tumors in women. However, the underlying molecular mechanisms of breast cancer are still far to clear. With the development of sequencing technology, we discovered that MAL2 is overexpressed in tumor tissues. But the major function of MAL2 in breast cancer has not to be well confirmed.

60 APPLIED LIFE SCIENCES↗

β1,6 GlcNAc branches-modified protein tyrosine phosphatase Mu attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways

The metastatic potential of malignant tumor has been shown to be correlated with the increased expression of tri- and tetra-antennary β1,6-N-acetylglucosamine (β1,6-GlcNAc) N-glycans. In this study, We found that GnT-V expression was negatively correlated with receptor protein tyrosine phosphatase type μ(RPTPμ) in human glioma tissues. To study whether RPTPμ is a novel substance of GnT-V which further affect RPTPμ′s downstream dephosphorylation function, we preform lentiviral infection with GnT-V gene to construct stably transfected GnT-V glial cell lines. We found RPTPμ undergone severer cleavage in GnT-V transfected glioma cells compare to Mock cells. RPTPμ intracellular domain fragments increased while β1,6-GlcNAc-branched N-glycans increased, in consistent with the decrease of RPTPμ′s catalytic activity. The results showed that abnormal glycosylation could decrease the phosphorylation activity of PTP μ, and affect PLCγ-PKC pathways. Both protease inhibitor Furin and N-glycan biosynthesis inhibitor swainsonine could decrease cell mobility in GnT-V-U87 transfectants and other glioma cell lines. All results above suggest increased post-translational modification of RPTPμ N-glycans by GnT-V attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways, and that the β1,6-GlcNAc-branched N-glycans of RPTPμ play a crucial role in glioma invasivity.

60 APPLIED LIFE SCIENCES↗

MiR-374b-5p-FOXP1 feedback loop regulates cell migration, epithelial-mesenchymal transition and chemosensitivity in ovarian cancer

MicroRNAs (miRNAs) are important regulators in tumorigenesis and progression of multiple human cancers, including ovarian cancer (OC). As a member of miRNAs family, miR-374b-5p has been reported to be a tumor suppressive gene in human cancers. In this study, the lower expression of miR-374b-5p was identified in OC tissues and cell liens using quantitative real time PCR (qRT-PCR). Forkhead box protein P1 (FOXP1) can act as an oncogene in human cancers. Mechanism experiments revealed that FOXP1 is a target of miR-374b-5p. Functionally, miR-374b-5p suppressed cell proliferation, migration and epithelial-mesenchymal transition (EMT) in ovarian cancer. Moreover, the sensitivity of OC cells to cisplatin was markedly enhanced by miR-374b-5p. However, FOXP1 reversed However, FOXP1 reversed miR-374b-5p-mediated biological functions. Previous reports demonstrated the inhibitory effect of FOXP1 on transcription FOXP1. Thus, we further examined the effect of FOXP1 on the transcription activity of miR-374b-5p in OC cells. The results showed that FOXP1 decreased miR-374b-5p expression by inhibiting the transcription activity of miR-374b-5p. Rescue assays revealed the regulatory effect of miR-374b-5p-FOXP1 feedback loop on ovarian cancer progression. In conclusion, miR-374b-5p-FOXP1 feedback loop regulates tumor progression and chemosensitivity in ovarian cancer.

60 APPLIED LIFE SCIENCES↗

Unravelling chloride transport/microstructure relationships for blended-cement pastes with the mini-migration method

A chloride mini-migration method is proposed to estimate effective diffusion coefficients at the scale of the cement paste and to investigate mechanisms with complementary microstructure analyses on the same material. Blended-cement pastes with a wide range of properties were investigated in this study: systems at w/b = 0.3–0.5 including Portland cement, white Portland cement, slag-Portland cement, fly ash, glass powder, and/or limestone and calcined clay. Comparisons showed the relative and combined importance of three main parameters on the effective diffusion coefficient: the porosity, the pore connectivity parameter and the conductivity of the pore solution (low values of the latter two are generally key aspects of the high resistance of blended-cement systems against chloride ingress). Notably, a general correlation for all the investigated systems was established between the effective diffusion coefficient and the bulk conductivity (whereas no simple correlation was observed between the effective diffusion coefficient and the formation factor or the pore connectivity parameter).

36 MATERIALS SCIENCE↗

Migration and accumulation of hydrous mantle incipient melt in the Earth's asthenosphere: Constraints from in-situ falling sphere viscometry measurements

The Earth's oceanic lithosphere-asthenosphere boundary (LAB) is marked by a notable decrease in seismic wave velocities and an increase in attenuation. This phenomenon is likely attributed to the accumulation of partial melt at the top of the asthenosphere. Nevertheless, the process involving the upward migration and aggregation of low-degree partial melts, highly likely to be mantle incipient melts in the asthenosphere, remains underexplored. Viscosity is a key factor controlling the flow of melts, thus in this study, we used In-situ X-ray falling sphere viscometry experiments to determine the viscosity of the mantle incipient melt containing 1.8–4.0 wt.% water at 1.5–6 GPa and 2100 K. We found that water and pressure can effectively decrease the viscosity of the mantle incipient melt. Therefore, the mantle incipient melts are highly mobile with a high segregation velocity in the deeper part of the asthenosphere. However, during ascent, their mobility diminishes due to an increase in viscosity and a decrease in water content. In conclusion, these mechanisms potentially contribute to the accumulation of partial melt at the top of the asthenosphere.

58 GEOSCIENCES↗

MOOSE-based Tritium Migration Analysis Program, Version 8 (TMAP8) for advanced open-source tritium transport and fuel cycle modeling

Tritium management is critical for the safety, sustainability, and economics of fusion energy systems, and advanced and reliable modeling tools help accelerate the development of tritium technologies. This paper presents the Tritium Migration Analysis Program, Version 8 (TMAP8), an open-source, MOOSE-based application developed to provide state-of-the-art tritium transport and fuel cycle modeling capabilities. TMAP8 aims to expand the capabilities of previous versions (i.e., TMAP4 and TMAP7) by leveraging modern computational techniques, ensuring high software quality assurance standards (key to building trust), and enabling multispecies, multiscale, and multiphysics simulations for integrated tritium transport modeling in complex geometries. This paper outlines TMAP8’s scope and rigorous development practices, emphasizing its transparency, accessibility, modularity, and reliability. We present the current suite of verification and validation cases based on those from TMAP4, demonstrating TMAP8’s accuracy and reliability against analytical solutions and experimental data. Additionally, the paper showcases TMAP8’s integrated fuel cycle modeling capabilities, highlighting its applicability at various scales and levels. The TMAP8 code and documentation are openly available, promoting collaborative development and widespread adoption within the fusion community. Future work will soon expand TMAP8’s verification and validation suite to include those from TMAP7 and other recent experimental studies for validation.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Hydromechanical modelling to evaluate impact of fault structure on CO 2 migration in stacked storage system

Faulting processes produce a complex fault damage zone (FDZ) having permeability variations over several orders of magnitude within a very short distance. In this study we use an example normal fault system from a depleted oil field in southern Louisiana with multiple stacked sand beds along the fault structure. Geostatistical techniques are used to introduce heterogeneities of several orders of magnitude over very short distances that honor the across- and along-fault architecture of the system. A total of 15 cases are simulated to account for the impact of a fragmented core, an intact core and a naturally fractured core on inter-sand leakage rates. The presented results show the complex nature of CO 2 migration within the fault structure, where an interplay between overcoming the fault core’s high capillary entry pressure and stress propagation in the vertical direction dictates the leakage direction and rates. It is observed that hydromechanical evolution of fracture flow properties may result in significant leakage from the storage zone. In one case with small caprock thickness, a loss of 18% of the total injected mass is observed. The results presented highlight some unique features of representative fault related leakage in stacked sand systems and thus will be beneficial for storage integrity analysis in these systems.

58 GEOSCIENCES↗

Tracking natural CO 2 migration through a sandstone aquifer using Sr, U and C isotopes: Chimayó, New Mexico, USA

The geochemical and isotopic characteristics of groundwaters in Chimayó, New Mexico, reflect processes that affect water quality in the Tesuque Aquifer, which overlies a leaking natural CO 2 source in a structurally complex region. In this study, select isotopes (δ 13 C, 87 Sr/ 86 Sr, 234 U/ 238 U) are applied to groundwaters to better understand CO 2 transport mechanisms and related water-rock interactions that impact Chimayó groundwater. Carbon stable isotope ratios of dissolved inorganic carbon (DIC; δ 13 CDIC = -15.10‰ to 4.50‰) identify a distinct source of upward-migrating CO 2 that interacts with the groundwater. Additionally, groundwater 87 Sr/ 86 Sr compositions (0.7098 to 0.7154) reflect intrusion of varying amounts of saline water associated with the high CO 2 source, while 234 U/ 238 U ratios corroborate presence of deep groundwater and suggest impacts from distinctive natural uranium sources are affecting groundwater. Previous work proposed two CO 2 transport mechanisms at the site: (1) dissolved in deep brine that underlies the aquifer and (2) in the gas phase; this study uses isotope mixing models to identify wells that are affected by these CO 2 transport mechanisms and demonstrates that both transport mechanisms are associated with impaired groundwaters. Overall, this study demonstrates that applying multiple isotope systems (δ 13 CDIC, 87 Sr/ 86 Sr, 234 U/ 238 U) is a dynamic tool for identifying and measuring the impact of CO 2 leakage from a sequestration site.

58 GEOSCIENCES↗

Formation, migration, and clustering energies of interstitial He in α-quartz and β-cristobalite

Precipitation of implanted helium (He) is detrimental to many nuclear materials. A solid in which implanted He does not precipitate, but rather remains in solution and diffuses readily is potentially of interest for applications requiring resistance to He-induced damage. Here we use density functional theory (DFT) calculations to examine He interstitial formation, migration, and clustering energies in two SiO 2 polymorphs: α-quartz and β-cristobalite. Our findings show greater He solubility and mobility in the latter than in the former. This difference appears to be due primarily to the unlike atomic-level structures of α-quartz and β-cristobalite, rather than their differing densities. Our findings also suggest that He is unlikely to cluster in either material. The behavior of He in α-quartz and β-cristobalite, and similar forms of silica make them promising materials for further investigation for potential use in applications requiring resistance to He-induced damage.

36 MATERIALS SCIENCE↗

Plutonium migration and phase evolution in irradiated U-Pu-Zr metallic fuels: An integrated EPMA-SEM-TEM study

Constituent redistribution is a defining feature of irradiated U-Pu-Zr metallic fuels, yet its mechanisms and effects on fuel performance are not sufficiently resolved to guide model development. Although decades of irradiation testing have established broad trends, a true mechanistic understanding of constituent redistribution has not been achieved. Here, in this study, we use electron probe microanalysis (EPMA), scanning electron microscopy (SEM), and transmission electron microscopy-based (TEM) selective area electron diffraction (SAED) on a EBR-II irradiated U-19 wt.% Pu-6 wt.% Zr fuel pin cross-section to correlate the composition, porosity, and crystallographic phases formed after irradiation. Constituent redistribution is thought to consist of three distinct zones, in which uranium and zirconium migrate while plutonium remains relatively unchanged. Our EPMA results resolve eight distinct compositional regions, and more importantly, show that plutonium redistributes alongside zirconium, contrary to historical assumptions. The distribution of fission products was highly asymmetric with a few large lanthanide precipitates observed at isolated sites on the pin periphery instead of a uniform distribution of smaller precipitates around the periphery. Using thermodynamic data from TAF-ID and the measured EPMA compositions, matrix phase fractions were predicted across the fuel radius. Phase predictions based on composition did not match TEM/SAED results, which revealed a much higher fraction of α−U phase than would be expected if phases were retained from reactor temperatures. These findings highlight the need for expanded SAED phase identification to capture post-irradiation and storage effects, as well as rigorous uncertainty quantification in fuel performance and phase diagram modeling to better constrain predictions from compositional data.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Bi{sub 1−x}Nb{sub x}O{sub 1.5+x} (x=0.0625, 0.12) fast ion conductors: Structures, stability and oxide ion migration pathways

A combined experimental and computational study of Bi{sub 1−x}Nb{sub x}O{sub 1.5+x} (x=0.0625 and 0.12) has been carried out using laboratory X-ray, neutron and electron diffraction, impedance measurements and ab-initio molecular dynamics. We demonstrate that Bi{sub 0.9375}Nb{sub 0.0625}O{sub 1.5625}, previously reported to adopt a cubic fluorite-type superstructure, can form two different polymorphs depending on the synthetic method: a metastable cubic phase is produced by quenching; while slower cooling yields a stable material with a tetragonal √2×√2×1 superstructure, which undergoes a reversible phase transition into the cubic form at ~680 °C on subsequent reheating. Neutron diffraction reveals that the tetragonal superstructure arises mainly from ordering in the oxygen sublattice, with Bi and Nb remaining disordered, although structured diffuse scattering observed in the electron diffraction patterns suggests a degree of short-range ordering. Both materials are oxide ion conductors. On thermal cycling, Bi{sub 0.88}Nb{sub 0.12}O{sub 1.62} exhibits a decrease in conductivity of approximately an order of magnitude due to partial transformation into the tetragonal phase, but still exhibits conductivity comparable to yttria-stabilised zirconia (YSZ). Ab-initio molecular dynamics simulations performed on Bi{sub 0.9375}Nb{sub 0.0625}O{sub 1.5625} show that oxide ion diffusion occurs by O{sup 2−} jumps between edge- and corner-sharing OM{sub 4} groups (M=Bi, Nb) via tetrahedral □M{sub 4} and octahedral □M{sub 6} vacancies. - Graphical abstract: Oxide ion migration in tetragonal Bi{sub 0.9375}Nb{sub 0.0625}O{sub 1.5625} occurs by O{sup 2−} jumps between edge- and corner-sharing OM{sub 4} groups (M=Bi, Nb) via tetrahedral M{sub 4} and octahedral M{sub 6} vacancies. - Highlights: • Bi{sub 0.9375}Nb{sub 0.0625}O{sub 1.5625} adopts a tetragonal √2×√2×1 fluorite superstructure. • Superstructure is due to ordering in the O-sublattice, with Bi/Nb disordered. • Bi{sub 0.9375}Nb{sub 0.0625}O{sub 1.5625} is a good oxide ion conductor. • O{sup 2−} jump between OM{sub 4} groups (M=Bi, Nb) via tetrahedral and octahedral vacancies.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗