Search Results (294)

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

Nodular Cast Iron (NCI, also known as ductile iron) is widely used in important components such as crankshafts for automotive engines and internal combustion engines, as well as storage and transportation containers for spent fuel in nuclear power plants, due to its good comprehensive mechanical properties such as strength, toughness, and wear resistance. The effect of temperature on the fracture behavior of NCI was investigated using compact tensile (CT) specimens at different temperatures. The results showed that the conditional fracture toughness parameter (K_Q) of the NCI specimens firstly increased and then decreased with decreasing temperature. The crack tip opening displacement δ_m shows a significant ductile–brittle transition behavior with the decreasing of temperature. δ_m remains constant in the upper plateau region but sharply decreases in the ductile–brittle region (−60 °C to −100 °C) and stabilizes at a smaller value in the lower plateau region. Multiscale fractographic analysis indicated that the fracture mechanism changed from ductile fracture (above −60 °C) to ductile–brittle mixed (−60 °C to −100 °C) and then to completely brittle fracture (below −100 °C). As the temperature decreased, the fracture characteristics changed from ductile dimples to dimple and cleavage mixed and then to brittle cleavage. Full article

Nucleocytoplasmic transport is crucial for neuronal cell physiology and defects are involved in neurodegenerative diseases like amyotrophic lateral sclerosis and Alzheimer’s disease, but also in ageing. Recent studies have suggested, that the classic nuclear import factor adapters KPNA3 (also named importin alpha4) and KPNA4 (also named importin alpha3) could be associated with the development of motor neuron diseases, a condition specifically affecting the neurons projecting from brain to spinal cord or from spinal cord to the muscles. Here we set out to analyze the neuronal function of mice deficient in KPNA3 (Kpna3-KO) or KPNA4 (Kpna4-KO). The motoric abilities and locomotion at different time points in ageing were tested to study the role of these two genes on motor neuron function. While we did not find deficits related to motor neurons in both mouse models, we discovered a hypermotoric phenotype in KPNA4-deficient mice. Attention deficit/hyperactivity disorder (ADHD) is caused by a combination of genetic, environmental and neurobiological factors and a number of genes have been suggested in genome-wide association studies to contribute to ADHD, including KPNA4. Here we provide supportive evidence for KPNA4 as a candidate pathogenic factor in ADHD, by analysing Kpna4-KO mice which show ADHD-like symptoms. Full article

Background/Objectives: Abnormal bile acid (BA) pool may play an important role in inducing liver damage in sepsis. Farnesoid X receptor (FXR) is a main negative feedback regulator of BA metabolism. This study aims to explore the protective effect and mechanism of the FXR agonist obeticholic acid (OCA) on liver dysfunction when sepsis occurs. Methods: A rat model of sepsis was induced by cecal ligation and puncture (CLP) for 24 h. Systematic inflammation, tissue injury, hepatic FXR, and BA transporter expression were investigated in the CLP rats and sham-operated control rats with and without OCA pre-treatment (10 mg/kg, gavage) at 2 h before operation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay was performed to access BA composition in the rats’ serum and livers. The injury and inflammatory effects of the elevated unconjugated BAs found in the CLP rats was further verified in a hepatic cell line BRL-3A in vitro. Results: Hepatic FXR was repressed in CLP rats, whereas OCA upregulated liver FXR and hepatic BA transporter expression, reduced total serum BA concentration, ameliorated the elevation of serum levels of IL-1β and IL-6, and improved liver and ileal tissue injuries. OCA administration reduced the elevated unconjugated BAs in both serum and liver, and effectively inhibited increases in cholic acid (CA), deoxycholic acid (DCA), and 7-ketoDCA concentrations in CLP rat livers. These BA fractions promoted the release of aspartate aminotransferase (AST) from BRL-3A cells and increased IL-6, CXCL2, and monocyte chemoattractant protein-1 (MCP-1) expression in the cells, along with enhanced transcription factor nuclear factor-κB activation. Conclusions: Liver inflammation and dysfunction during sepsis is attributable to significant changes in bile acid composition in the blood and liver. FXR activation reduces systemic inflammation and liver dysfunction by regulating bile acid homeostasis, especially inflammatory unconjugated bile acid components. Full article

Ecologically sustainable economic development is increasingly recognized as essential to global efforts to improve and protect environmental and socio-economic conditions. The transportation sector is also important regarding the movement of human beings and goods. Fossil fuels are primarily used in transport vehicles and emit carbon dioxide into the atmosphere. Hence, innovative investments in the transportation system and the use of renewable energy play a key role in overcoming this lingering problem. This study utilizes nonlinear autoregressive distributed lag (NARDL) methods to uncover key drivers influencing innovative investments in the transportation sector and the impact of renewable energy use on environmental sustainability in France between 1995 and 2020. The results indicate that renewable energy use and transport infrastructure innovations positively and negatively impact environmental sustainability. Both variables have different influences on the dependent variable depending on the economic shock period. Based on the outcomes, this study offers the following significant policy insights: (i) France could invest in innovations in renewable energy sourcing and incentivize switching from combustion engine-based transport systems. (ii) France should commit to the Europe 2020 strategy for green growth to ensure resource efficiency and promote environmental sustainability, which requires a coordinated effort to invest in smart transport systems that leverage technologies like the Internet of Things, artificial intelligence, and big data analytics. (iii) Given that two-thirds of France’s electricity is produced from nuclear sources, the government needs to implement policies in the renewable energy sector to reduce over-reliance on nuclear energy sourcing. Full article

Estrogen-related receptors (ERRs) are important transcription factors within the nuclear receptor family that regulate cellular energy storage and consumption by binding to estrogen-related receptor response elements (ERREs) on gene promoters. While ERRs’ role in vertebrates is well-studied, their molecular mechanisms in insect metabolism and development remain unclear. This study systematically summarizes the functions of ERRs in insects, focusing on silkworms by analyzing gene functions and comparing databases. ERRE-like elements were identified in the 2000 bp upstream promoter regions of 69 metabolism-related silkworm genes. Furthermore, electrophoretic mobility shift assays (EMSAs) revealed that ERREs within the promoters of 15 genes related to sugar, fat, and protein metabolism specifically bind to ERR. Notably, an ERRE in the promoter of the trehalose transporter 1 gene (BmTret1), crucial for trehalose homeostasis in insect hemolymph, exhibited significantly enhanced activity in ERR-overexpressing cells. These findings suggest that ERR is a potential regulatory factor in silkworm metabolism and refine its metabolic regulatory network. This study highlights the broader and more critical role of ERR in insects than that previously recognized, contributing to a deeper understanding of insect metabolism and its potential applications in related fields. Full article

With increasing exterior temperature, steel corrosion and concrete disintegration in RC (reinforced concrete) are severe due to the increased transport of harmful ions. A durability design for the intended service life should be ensured for the changing exterior conditions. In this study, for the concrete used in a UAE (United Arab Emirates) nuclear power plant structure, the diffusion coefficient of sulfate ions affected by temperature was evaluated through a natural diffusion cell test, and the service life in the structure was calculated through deterministic and probabilistic methods. As the temperature increased from 20 °C to 50 °C, the results decreased rapidly due to an enlarged diffusion coefficient, and its variation significantly increased with unstable ion transport. In the probabilistic method, the effect of the mean and COV (coefficient of variation) for each design parameter on service life was analyzed, which suggested the importance of enough cover depth design with COV under 0.2. Full article

Human papillomavirus (HPV) 16 is transported in a retrograde fashion from the cell surface to the Golgi apparatus. Prior to mitosis, the virus loses association with the Golgi and, following nuclear envelope breakdown, is found associated with the condensed mitotic chromatin. The intervening steps have not been well defined. It was previously demonstrated that the virus is transported to the mitotic chromosomes in vesicles. Here, we describe the role of the endoplasmic reticulum (ER) in the post-Golgi trafficking and the importance of the ER-generated coat protein complex II (COPII) anterograde trafficking pathway in HPV infection. HPV pseudovirus (PsV) colocalized with COPII components and silencing of this pathway inhibited HPV infection. Additionally, the inner COPII coat protein, Sec24b, could be biochemically isolated in association with HPV capsid proteins. This study provides insight into the mechanism of post-Golgi HPV trafficking. Full article

The type IV secretion system (T4SS) is an important virulence factor of Brucella. T4SS secretes 16 effector proteins, which affect the intracellular transport of Brucella-containing vacuoles and regulate the host immune response, helping Brucella survive and replicate in host cells. In our previous crotonylation proteomics data of HEK-293T cell proteins triggered by BspF, we found BspF crotonylated on TRIM38, which is an important modulator in the pathways of inflammation, and the crotonylation site is K142. Therefore, it is speculated that BspF may be involved in the regulation of host inflammatory response during Brucella infection. In this study, we found that BspF-mediated TRIM38K142 crotonylation promotes the ubiquitination of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6), leading to the degradation of TRAF6 and thereby inhibiting the transduction of Nuclear factor-kappaB (NF-κB), p38 Mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinases (JNK) MAPK signaling pathways and the secretion of pro-inflammatory factors IL-6 and IL-8, which finally helps Brucella promote intracellular survival. This study provides a new theoretical basis for the intracellular survival of host innate immunity through the T4SS, provides new insights into the pathogenic mechanism and treatment of Brucella, and provides an important reference for the study of non-histone crotonylation function. Full article

With the transformation of the world’s energy structure and the promotion of clean energy, nuclear power has come to the fore as an efficient and environmentally friendly form of energy. As critical components in the operation of nuclear power plants (NPPs), suction and transportation devices for thermal traps—designed to prevent and control floating bodies—are directly linked to the safety of power generation, the stability of operations, and the reliability of the power grid in NPPs. Technical research and advancements in these devices play a crucial role in enhancing their effectiveness. In view of the intrusion and blockage of floating bodies in the sewage network pocket of the water intake with the cold-source system for coastal NPPs, the key technologies to prevent and control floating bodies that may impair cooling resources in NPPs’ thermal traps is discussed. This paper introduces the safety risks and social impacts associated with water intake, highlights the importance of the water-intake system, and discusses the interception and transportation mechanisms in NPPs. The progress of explosive floating bodies’ interception, cleaning, suction, transportation, and intelligent monitoring technology is introduced through the technical progress in the types of floating bodies, as well as cutting, crushing, suction, and transportation devices. The technical progress of efficient treatment is realized, which provides reference for the research and practice of the key technologies for suction and transportation devices to prevent and control floating bodies’ suction and transportation devices in NPPs’ thermal traps. Full article

As one of the important components of placental structure, the integrity of placental trophoblast cells is crucial for placental function. When oxidative stress continues to act on placental trophoblast cells, it can cause changes in placental structure and function. Research has shown that folic acid (FA) has a certain alleviating effect on the functional damage of trophoblast cells caused by oxidative stress, but the mechanism of action is still unclear. Therefore, this study focuses on bovine placental trophoblast cells (BPTCs) to explore the effects and mechanisms by which FA regulates oxidative stress in cells, with the aim of providing a theoretical foundation for improving the reproductive performance of cows. The results show that, compared with the H₂O₂ group, the FA+ H₂O₂ group showed an increase in the cell proliferation index (PI), superoxide dismutase 2 (SOD2), glutathione peroxidase (GSH-px), and catalase (CAT) mRNA expression and total antioxidant capacity (T-AOC) of cells, while the content of reactive oxygen species (ROS) decreased. In addition, the mRNA expression of tight junction factors, nutrient transporters, placental functional factors, mammalian rapamycin (mTOR) and its downstream factors, and nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream factors in the FA+ H₂O₂ group increased, while the protein abundance of nuclear NRF2 decreased. After treatment with the inhibitor ML385, it was found that the protective effect of FA on H₂O₂-induced cellular oxidative damage was alleviated. These results indicate that FA can regulate the NRF2/mTOR signaling pathway, promote the expression of antioxidant factors, and alleviate the damage to the cell barrier and nutrient transport function in BPTCs caused by oxidative stress. Full article

Karyopherins, carrier proteins that recognize particular cargo protein patterns known as nuclear localization signals (NLSs), mediate the nuclear translocation of big proteins. In order to better understand the process of nuclear transport of proteins and create the groundwork for the development of innovative treatments that specifically target importins, it is imperative to clarify the intricate interactions between nuclear transporters and their cargo proteins. Until recently, very few NLSs have been documented. In the current work, an in silico method was used to identify NLSs for importin 8. It was determined that the sequence RRKLPVGRS serves as a recognition motif for importin 8 binding a karyopherin that is involved in the nuclear transportation of several important proteins like AGOs, SMADs, RPL23A, and TFE3. The sequence was validated in vitro in the breast cancer cell line T47D. This work subscribes to the effort to clarify the intricate relationships between nuclear transporters and their cargo proteins, in order to better understand the mechanism of nuclear transport of proteins and lay the groundwork for the development of novel therapeutics that target particular importins and have an immediate translational impact. Full article

Solar thermal energy is one of the most interesting sustainable solutions for decarbonizing the energy sector. Integrating solar collectors with other energy sources is common, as seen in domestic heating, where solar collectors are combined with common heaters to reduce fuel consumption (gasoline, electricity, gas, and biomass) and therefore, the energy cost. Similarly, this concept can be applied to nuclear energy, where the reduction in nuclear fuel consumption is very strategic for decreasing not only its cost but also the risk in handling, transportation, and storage (both the fuel and the nuclear waste as well). Nuclear energy, on the other hand, seems to be very useful in reducing the land occupation of concentrated solar power plants (CSPs) and helping a more constant production of electricity, both points being two important bottlenecks of CSP technologies. CSP and nuclear reactors, on the other hand, share common heating technologies and both can produce energy without CO₂ emissions. Solar and nuclear energy, especially with the advent of the fourth generation of small modular reactors (SMRs), present a compelling opportunity for sustainable electricity generation. In this work, we present a brief review of CSP technology, a brief review of SMR concepts and development, and a brief overview of the combination of these two technologies. The review shows that in general, combined SMR + CSP technologies offer several advantages in terms of a strong reduction in the solar field extension areas, improved dispatchability of energy, improved efficiency of the SMRs, and, in particular, lower nuclear fuel consumption (hence, e.g., with a lowered refueling frequency). Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its dense fibrotic stroma that promotes drug resistance and tumor progression. While patient-derived organoids (PDOs) have emerged as promising tools for modeling PDAC and evaluating therapeutic responses, the current PDO models grown in soft matrices fail to replicate the tumor’s stiff extracellular matrix (ECM), limiting their predictive value for advanced disease. Methods: We developed a biomimetic model using gelatin-based matrices of varying stiffness, achieved through modulated transglutaminase crosslinking rates, to better simulate the desmoplastic PDAC microenvironment. Using this platform, we investigated organoid morphology, proliferation, and chemoresistance to gemcitabine (Gem) and its lipophilic derivative, 4-N-stearoyl gemcitabine (Gem-S). Mechanistic studies focused on the interplay between ECM stiffness, hypoxia-inducible factor (HIF) expression, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in drug resistance. Results: PDAC organoids in stiffer matrices demonstrated enhanced stemness features, including rounded morphology and elevated cancer stem cell (CSC) marker expression. Matrix stiffness-induced gemcitabine resistance correlated with the upregulation of ABC transporters and oxidative stress adaptive responses. While gemcitabine activated Nrf2 expression, promoting oxidative stress mitigation, Gem-S suppressed Nrf2 levels and induced oxidative stress, leading to increased reactive oxygen species (ROS) and enhanced cell death. Both compounds reduced HIF expression, with gemcitabine showing greater efficacy. Conclusions: Our study reveals ECM stiffness as a critical mediator of PDAC chemoresistance through the promotion of stemness and modulation of Nrf2 and HIF pathways. Gem-S demonstrates promise in overcoming gemcitabine resistance by disrupting Nrf2-mediated adaptive responses and inducing oxidative stress. These findings underscore the importance of biomechanically accurate tumor models and suggest that dual targeting of mechanical and oxidative stress pathways may improve PDAC treatment outcomes. Full article

A nuclear export signal (NES) is a cluster of hydrophobic amino acids that can maintain the dynamic shuttling of target proteins between the nucleus and cytoplasm. Bioinformatics analysis showed that the hydrophobic region of ⁹²PLLLHKFLLA in Bm65 is very likely to be an NES and may be involved in the production of infectious virions. In this study, we generated several mutations in ⁹²PLLLHKFLLA of Bm65, which were further used to generate recombinant viruses to study their roles in viral propagation. Subcellular analysis revealed that the ⁹²PLLLHKFLLA sequence was an NES involved in the dynamic transport of Bm65. Mutations in the hydrophobic region could block the formation and accumulation of Bm65 aggregates, resulting in a uniform distribution of Bm65 in BmN cells. The ribosomal protein L13 (RPL13) of silkworms was previously reported to interact with Bm65. Here, intracellular co-localization analysis showed that the interaction between Bm65 and RPL13 was regulated by the ⁹²PLLLHKFLLA of Bm65. In summary, the interaction between Bm65 and RPL13 is essential for the production and accumulation of Bm65 aggregates and may play an important role in the regulation of viral propagation. Full article