Search Results (341)

This study improved the thermal damping of concrete with rice husk ash (RHA)–fly ash (FA) matrix and three phase-change material (PCM) aggregates with phase change temperatures between −15 and 5 °C, which are expected to reduce winter energy consumption in cold regions when used as building envelope structures. Firstly, the strength of concrete was studied. Secondly, the dynamic and transient thermal response of concrete was evaluated through thermal conductivity and thermal diffusivity. Based on nuclear magnetic resonance experiments, the changes in the pore volume and fractal dimension of RHA–FA matrix and PCM aggregate added to concrete were studied. Through correlation analysis, a macroscopic performance prediction model based on pore characteristics was obtained. The results indicated that the incorporation of PCM aggregate reduced concrete strength, while an appropriate RHA–FA matrix contributed to enhancing concrete strength. Both the PCM aggregate and RHA–FA matrix were beneficial for improving the thermal damping properties of concrete. For 15% RHA–30% FA 100% PCM concrete, the thermal conductivity can be reduced by 53%, the thermal diffusivity can be reduced by 64%, the limiting temperature decreased by 5.5 °C, and the thermal damping coefficient increased by 48%. The nuclear magnetic resonance test results showed that PCM aggregate increased the pore volume and decreased the fractal dimension, while an appropriate RHA–FA matrix helped to reduce the pore volume. The macroscopic properties of RHA–FA–PCM aggregate concrete were highly correlated with the capillary pore volume and fractal dimension. A two-parameter prediction model based on pore characteristics can effectively predict the macroscopic properties of concrete. Full article

Lithium hydride (LiH) is one promising material for nuclear reactor shielding due to its high hydrogen content, but its poor mechanical strength and thermal conductivity pose challenges for fabricating large, crack-free ceramic components via conventional sintering. This study explores microwave sintering as a potential solution to enhance heating uniformity and reduce thermal stress during densification of bulk LiH ceramics. Using implicit function and level set methods, we numerically simulated the microwave field distribution and thermal response in both stationary and rotating samples. The results show that rotational heating improves temperature uniformity by up to 12.9% for specific samples, although uniform temperature control remains difficult through rotation alone. To mitigate stress accumulation from thermal gradients, we propose a cyclic sintering–resting strategy, which leverages LiH’s tensile strength–temperature envelope to guide safe and efficient processing. This strategy successfully reduced total sintering time from several days to 1.63 h without inducing cracks. Our findings offer practical insights into optimizing microwave sintering parameters for large-scale LiH ceramic production and contribute to enabling its application in advanced nuclear shielding systems. Full article

Under the carbon neutrality framework, multiple coastal nuclear power plants in China have received construction approval. This development has drawn increased attention to the impact of thermal discharge on the marine environment. However, research on the diffusion effects caused by different thermal discharge configurations remains limited. This study focused on the Jinqimen Nuclear Power Plant. It employed the MIKE 3 (2014) three-dimensional numerical model, combined with field observations, to systematically investigate thermal plume dispersion. Specifically, it examined the effects of different jet angles at the discharge outlet (0°, 30°, 45°, 60°, 90°, and free diffusion conditions). The results indicate that the jet angle significantly influences the thermal rise envelope area and thermal stratification characteristics. Under free diffusion conditions (without jet velocity), the thermal rise area is the largest, with high-temperature zones concentrated near the surface. As the jet angle increases from 0° to 90°, the area of low-temperature rise gradually decreases, while the area of high-temperature rise expands. Among all tested configurations, the 30° jet angle exhibits the best overall performance. It demonstrates high thermal diffusion efficiency and strong heat dilution capacity. Moreover, it results in relatively smaller temperature rise areas at the surface, middle, and bottom layers. Additionally, tidal dynamics directly affect the thermal dispersion pattern. Smaller high-temperature rise areas are observed during peak flood and ebb tides. In contrast, heat accumulation is more likely to occur during slack tide periods. This study provides a scientific basis for optimizing the layout of nuclear power plant discharge outlets. It also serves as an important reference for mitigating thermal pollution and reducing ecological impacts of coastal nuclear power plants. 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 cancer chemotherapy regimen of a taxane and platinum combination was developed more than forty years ago, yet remains the cornerstone of treatment for several major cancer types today. Although many new agents targeting cancer genes and pathways have been developed and evaluated, none have been sufficient to replace the long-established taxane/platinum combination. This leads us to ponder why, after four decades of colossal efforts, multiple discoveries, and tremendous advances in understanding gene mutations and biology, the development of conceptually superior targeted therapies has not yet achieved overwhelming success in replacing cytotoxic chemotherapy. The concept of targeted therapy is based on the idea that blocking the altered pathway(s) crucial for cancer development (and maintenance), the disturbance in cellular signaling, metabolism, and functions will make the targeted cancer cells unfit and trigger programmed cell death in cancer cells, but without the significant side effects that limit chemotherapy. We propose that the lack of anticipated triumphs of targeted therapy stems from the desensitization of programmed cell death pathways during neoplastic transformation and malignant progression of cancer cells. This renders the targeting drugs largely ineffective at killing cancer cells and mostly insufficient in clinical implements. Recent advances in understanding suggest that, in contrast to targeted therapies, taxanes and platinum agents kill cancer cells by physical rupturing nuclear membranes rather than triggering apoptosis, making their effect independent of the intrinsic cellular programmed cell death mechanism. This new recognition of the non-programmed cell death mechanism in the success of chemotherapeutic agents, such as taxanes and platinum, may inspire oncologists and cancer researchers to focus their efforts more productively on developing effective non-programmed cell death cancer therapies to replace or significantly improve the application of the current standard taxane/platinum regimens. Full article

Cells respond to external mechanical cues and transduce these forces into biological signals. This process is known as mechanotransduction and requires a group of proteins called mechanosensors. This peculiar class of receptors include extracellular matrix proteins, plasma membrane proteins, the cytoskeleton and the nuclear envelope. These cell components are responsive to a wide spectrum of physical cues including stiffness, tensile force, hydrostatic pressure and shear stress. Among mechanotransducers, the Transient Receptor Potential (TRP) and the PIEZO family members are mechanosensitive ion channels, coupling force transduction with intracellular cation transport. Their activity contributes to embryo development, tissue remodeling and repair, and cell homeostasis. In particular, vessel development is driven by hemodynamic cues such as flow direction and shear stress. Perturbed mechanotransduction is involved in several pathological vascular phenotypes including hereditary hemorrhagic telangiectasia. This review is conceived to summarize the most recent findings of mechanotransduction in development. We first collected main features of mechanosensitive proteins. However, we focused on the role of mechanical cues during development. Mechanosensitive ion channels and their function in vascular development are also discussed, with a focus on brain vessel morphogenesis. Full article

Phosphodiesterase 4 (PDE4) is a key regulator of cyclic adenosine monophosphate (cAMP) signalling in cardiomyocytes, controlling contractility, calcium handling, and hypertrophic responses. PDE4 provides spatial and temporal precision to cAMP signalling, particularly under β-adrenergic stimulation, through its compartmentalised activity in subcellular nanodomains, including the sarcoplasmic reticulum, plasma membrane and nuclear envelope. This review highlights the cardiac PDE4 isoforms PDE4A, PDE4B and PDE4D, focusing on their distinct localisation and contributions to cardiac physiology and pathophysiology, particularly in heart failure and arrhythmias. Although PDE4 plays a smaller role in overall cAMP hydrolysis in human hearts than in rodents, its compartmentalised function remains critical. Recent therapeutic advances have shifted from pan-PDE4 inhibitors to isoform-specific approaches to enhance efficacy while minimising systemic toxicity. We discuss the potential of selective PDE4 modulators, gene therapies and combination strategies in restoring cAMP compartmentation and preventing maladaptive cardiac remodelling. By integrating rodent and human studies, this review underscores the translational challenges and therapeutic opportunities surrounding PDE4, positioning it as both a key regulator of cardiac signalling and a promising target for heart failure therapies. Full article

The open reading frame 103 (p48) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is one of the 38 core baculovirus genes. p48 has been shown to be essential for the production of infectious budded virions (BVs), nuclear egress of nucleocapsids, envelopment of the nucleocapsid, and embedding of occlusion-derived virions (ODVs) into occlusion bodies (OBs). However, the structure–function relationship of P48 remains unclear. In this study, we showed that four conserved cysteines (C127, C130, C138, and C141) in P48 may form a zinc finger motif based on a predicted structure analysis, and we investigated the roles of these cysteines in P48 function. AcMNPV bacmids lacking p48 or containing mutated p48 were generated. Transfection/infection assays showed that C127, C130, C138, and C141 in P48 were crucial for infectious BV production. Electron microscopy analysis further confirmed that these four cysteines played critical roles in the transport of nucleocapsids out of the nucleus for BV production, and in ODV envelopment. These results demonstrate that the conserved cysteines C127, C130, C138, and C141, related to the putative zinc finger motif, are critical for P48 function in baculovirus infection. Full article

Structural virology has emerged as the foundation for the development of effective antiviral therapeutics. It is pivotal in providing crucial insights into the three-dimensional frame of viruses and viral proteins at atomic-level or near-atomic-level resolution. Structure-based assessment of viral components, including capsids, envelope proteins, replication machinery, and host interaction interfaces, is instrumental in unraveling the multiplex mechanisms of viral infection, replication, and pathogenesis. The structural elucidation of viral enzymes, including proteases, polymerases, and integrases, has been essential in combating viruses like HIV-1 and HIV-2, SARS-CoV-2, and influenza. Techniques including X-ray crystallography, Nuclear Magnetic Resonance spectroscopy, Cryo-electron Microscopy, and Cryo-electron Tomography have revolutionized the field of virology and significantly aided in the discovery of antiviral therapeutics. The ubiquity of chronic viral infections, along with the emergence and reemergence of new viral threats necessitate the development of novel antiviral strategies and agents, while the extensive structural diversity of viruses and their high mutation rates further underscore the critical need for structural analysis of viral proteins to aid antiviral development. This review highlights the significance of structure-based investigations for bridging the gap between structure and function, thus facilitating the development of effective antiviral therapeutics, vaccines, and antibodies for tackling emerging viral threats. Full article

One of the primary challenges for future nuclear fusion power plants is understanding how neutron irradiation affects reactor materials. To tackle this issue, the IFMIF-DONES project aims to build a facility capable of generating a neutron source in order to irradiate different material samples. This will be achieved by colliding a deuteron beam with a lithium jet. In this work, within the DONES-FLUX project, deep learning surrogate models are applied to the design and optimization of the IFMIF-DONES linear accelerator. Specifically, neural operators are employed to predict deuteron beam envelopes along the longitudinal axis of the accelerator and neutron irradiation effects at the end, after the beam collision. This approach has resulted in models that are able of approximating complex simulations with high accuracy (less than 17% percentage error for the worst case) and significantly reduced inference time (ranging from 2 to 6 orders of magnitude) while being differentiable. The substantial speed-up factors enable the application of online reinforcement learning algorithms, and the differentiable nature of the models allows for seamless integration with differentiable programming techniques, facilitating the solving of inverse problems to find the optimal parameters for a given objective. Overall, these results demonstrate the synergy between deep learning models and differentiable programming, offering a promising collaboration among physicists and computer scientists to further improve the design and optimization of IFMIF-DONES and other accelerator facilities. This research will lay the foundations for future projects, where optimization efforts with differentiable programming will be performed. Full article

Some Pseudococcidae species interact with Coffea arabica’s roots and are associated with basidiomycete fungi. The fungal mycelium envelops the roots, which hinders their water and nutrient absorption. Combined with the feeding activity of the insects, this results in chlorosis, defoliation, and even plant death. Despite the significance of these interactions, they remain under-studied. To investigate the relationship between sporocarps found at the base of coffee trees, the cysts covering their roots, and the mealybug insects within them, samples of these three organisms—sporocarps, cysts, and mealybugs—were collected from 27 coffee plants across three farms in the departments of Norte de Santander and Quindío, Colombia. Fungi and cysts were identified by sequencing a nuclear gene region of the 28S large ribosomal subunit (28S rDNA) using the primers LSU200-F and LSU481-R. Fungal identification was further confirmed through classical taxonomy. Mealybugs were identified by sequencing a region of the mitochondrial gene Cytochrome C oxidase subunit I (COI) with CIF-CIR primers, corroborated through classical taxonomy. This study identified four fungal species associated with four species of Pseudococcidae. The fungus Phlebopus beniensis was associated with the mealybugs Pseudococcus elisae, Dysmicoccus neobrevipes, D. brevipes, and Pseudococcus nr. sociabilis. Phlebopus portentosus was linked to D. neobrevipes, while Xerophorus olivascens and Boletinellus rompelii were associated with other Pseudococcidae species. Additionally, the fungus Pseudolaccaria pachyphylla was found in coffee plants harboring mealybugs. These findings confirm the existence of specific associations between fungal species and mealybug insects that affect coffee plants. Full article

Emery–Dreifuss muscular dystrophy type 1 (EDMD1) is a rare genetic disease caused by mutations in the EMD gene, which encodes the nuclear envelope protein emerin. Despite understanding the genetic basis of the disease, the molecular mechanism underlying muscle and cardiac pathogenesis remains elusive. Progress is restricted by the limited availability of patient-derived samples; therefore, there is an urgent need for human-specific cellular models. In this study, we present the generation and characterization of induced pluripotent stem cell (iPSC) lines derived from EDMD1 patients carrying EMD mutations that lead to truncated or absent emerin, together with iPSCs from healthy donor. The patient-specific iPSCs exhibit stable karyotypes, maintain appropriate morphology, express pluripotency markers, and demonstrate the ability to differentiate into three germ layers. To model EDMD1, these iPSCs were differentiated into myogenic progenitors, myoblasts, and multinucleated myotubes, which represent all stages of myogenesis. Each developmental stage was validated by the presence of stage-specific markers, ensuring the accuracy of the model. We present the first iPSC-based in vitro platform that captures the complexity of EDMD1 pathogenesis during myogenesis. This model can significantly contribute to understanding disease mechanisms and develop the targeted therapeutic strategies for EDMD1. Full article

Non-centrosomal microtubule-organizing centers (ncMTOCs) are important for the function of differentiated cells. Yet, ncMTOCs are poorly understood. Previously, several components of the nuclear envelope (NE)-MTOC have been identified. However, the temporal localization of MTOC proteins and Golgi to the NE and factors controlling the switch from a centrosomal MTOC to a ncMTOC remain elusive. Here, we utilized the in vitro differentiation of C2C12 mouse myoblasts as a model system to study NE-MTOC formation. We find based on longitudinal co-immunofluorescence staining analyses that MTOC proteins are recruited in a sequential and gradual manner to the NE. AKAP9 localizes with the Golgi to the NE after the recruitment of MTOC proteins. Moreover, siRNA-mediated depletion experiments revealed that Mbnl2 is required for proper NE-MTOC formation by regulating the expression levels of AKAP6β. Finally, Mbnl2 depletion affects Pcnt isoform expression. Taken together, our results shed light on how mammals post-transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify Mbnl2 as a novel modulator of ncMTOCs in skeletal muscle cells. Full article

In the last decades, the study of many nuclear envelope components in Dictyostelium amoebae has revealed conserved mechanisms of nuclear envelope dynamics that root back unexpectedly deep into the eukaryotic tree of life. In this review, we describe the state of the art in nuclear envelope research in this organism starting from early work on nuclear pore complexes to characterization of the first true lamin in a non-metazoan organism and its associated nuclear envelope transmembrane proteins, such as the HeH-family protein Src1 and the LINC complex protein Sun1. We also describe the dynamic processes during semi-closed mitosis, including centrosome insertion into the nuclear envelope, and processes involved in the restoration of nuclear envelope permeability around mitotic exit and compare them to the situation in cells with open or fully closed mitosis. Full article

Cardiac laminopathies encompass a wide range of diseases caused by defects in nuclear envelope proteins, including cardiomyopathy, atrial and ventricular arrhythmias and conduction system abnormalities. Two genes, namely LMNA and EMD, are typically associated with these disorders and are part of the routine genetic panel performed in affected patients. Yet, there are other markedly fewer known proteins, the nesprins, encoded by SYNE genes, that play a pivotal role in connecting the nuclear envelope to cytoskeletal elements. So far, SYNE gene variants have been described in association with neurodegenerative diseases; their potential association with cardiac disorders, albeit anecdotally reported, is still largely unexplored. This review focuses on the role of nesprins in cardiomyocytes and explores the potential clinical implications of SYNE variants by presenting five unrelated patients with distinct cardiac manifestations and reviewing the literature. Emerging research suggests that SYNE-related cardiomyopathies involve disrupted nuclear–cytoskeletal coupling, leading to impaired cardiac function. Understanding these mechanisms is critical for furthering insights into the broader implications of nuclear envelope proteins in cardiac health and for potentially developing targeted therapeutic strategies. Additionally, our data support the inclusion of SYNE genes in the cardiac genetic panel for cardiomyopathies and cardiac conduction disorders. Full article