Search Results (137)

The storage and monitoring of nuclear fuel, whether spent or fresh, are key components of the nuclear energy life cycle, with significant implications for safety and sustainability. With the global focus on carbon neutrality, interest in advanced management solutions is rising. This paper provides a comprehensive analysis of modern technologies for the design, storage, and monitoring of nuclear fuel, highlighting current trends and future challenges. The study encompasses both spent and fresh nuclear fuel, with a focus on radiological safety, structural integrity, and digital monitoring. Data were organized into the following categories: storage types (wet/dry), monitored parameters, surveillance technologies (sensors, AI, IoT, and Digital Twin), simulation models, and emerging directions. A comparison between fresh and spent fuel shows a clear shift toward intelligent systems using non-invasive sensors, deep-learning algorithms, and decentralized architectures (e.g., blockchain-IoT). Despite progress, challenges remain, such as limited interoperability across system generations and insufficient experimental validation. This paper provides a solid foundation for researchers, suggesting future directions that include the full integration of AI in monitoring, broader numerical simulations for reliability, and the standardization of digital interfaces. These measures could significantly enhance the safety and efficiency of nuclear fuel storage systems. Full article

B-raf (rapidly accelerated fibrosarcoma) is a crucial player within the ERK/MAPK signaling pathway. In the CNS, B-raf has been implicated in neuronal differentiation, long-term memory, and major depression. Mice with forebrain neuron-specific B-raf knockout show behavioral deficits in spatial learning tasks and impaired hippocampal long-term potentiation (LTP). To elucidate the mechanism(s) underlying diminished synaptic plasticity in B-raf-deficient mice, we performed whole-cell recordings from CA1 pyramidal cells in hippocampal slices of control and B-raf mutant mice. We found that the NMDA/AMPA ratio of excitatory postsynaptic currents (EPSCs) at the Schaffer collateral—CA1 pyramidal cell synapses was significantly reduced in B-raf mutants, which would at least partially account for their impaired LTP. Interestingly, the reduced NMDA component of field postsynaptic potentials in mutant preparations was partially reinstated by blocking the apamin-sensitive small-conductance Ca²⁺-activated K⁺ (SK) channels, which have also been reported to modulate hippocampal LTP and learning tasks. To determine the impact of B-raf-dependent signaling on SK current, we isolated the apamin-sensitive tail current after a strong depolarizing event and found indeed a significantly bigger SK current in B-raf-deficient cells compared to controls, which is consistent with the reduced action potential firing and the stronger facilitating effect of apamin on CA1 somatic excitability in B-raf-mutant hippocampus. Our data suggest that B-raf signaling readjusts the delicate balance between NMDA receptors and SK channels to promote synaptic plasticity and facilitate hippocampal learning and memory. Full article

Plants dynamically regulate ions in the tree to defend against abiotic stresses such as drought and saline-alkali, However, it is not clear how ‘Junzao’ jujube regulates ions to maintain a normal life cycle under saline-alkali stress. Therefore, in this study, the roots of 10-year old steer jujube trees were watered using a saline and alkaline gradient solution simulating the main salt (NaCl) and alkali (NaHCO₃) of Aral with NaCl:NaHCO₃ = 3:1 gradient of 0, 60, 180, and 300 mM, and three jujube trees with uniform growth were taken as samples in each treatment plot, and the ion contents of potassium (K), sodium (Na), calcium (Ca), magnesium (Mg), iron (Fe), manganese (Mn), zinc (Zn) and carbon (C) in each organ of the fruit at the dot red period (S1) and full-red period (S2) were determined, in order to elucidate the relationship between physiological adaptation mechanisms of saline-alkali tolerance and the characteristics of mineral nutrient uptake and utilisation in jujube fruit. The results showed that under saline-alkali stress, Na was stored in large quantities in the roots, Ca and Mg in the perennial branches at S1, Na and Fe in the leaves at S2, and K, Mg and Mn in the perennial branches. There was no significant difference in the distribution of C content in various organs of ‘Junzao’. Compared with CK (0 mM), under salinity stress, the K content in the leaves was significantly reduced at S1 and S2, and the K/Na ratios remained > 1.0. At S2, under medium and high concentrations of saline-alkali stress (180–300 mM), the K/Na is less than 1, and the ionic homeostasis was disrupted, and the leaves die and fall off, and the Na is excreted from the body. The selective transport coefficients SK/Na, SCa/Na and SMg/Na from root to leaf showed a downward trend at S1, but still maintained positive transport capacity. At S2, this stage is close to leaf fall, the nutrient transport coefficient is less than 1, and a large amount of nutrients are returned to the perennial branches and roots occurred. These results indicated that the mechanism of nutrient regulation and salt tolerance in jujube trees was different at different growth stages. Full article

Aldehyde dehydrogenase 2 (ALDH2) is a crucial detoxifying enzyme that eliminates toxic aldehydes. ALDH2 deficiency has been linked to various human diseases, including certain cancers. We have previously reported ALDH2 downregulation in human melanoma tissues. Here, we further investigated the biological significance of ALDH2 downregulation in this malignancy. Analysis of TCGA dataset revealed that low ALDH2 expression correlates with poorer survival in metastatic melanoma. Examination of human metastatic melanoma cell lines confirmed that most had ALDH2 downregulation (ALDH2-low) compared to primary melanocytes. In contrast, a small subset of metastatic melanoma cell lines exhibited normal ALDH2 levels (ALDH2-normal). CRISPR/Cas9-mediated ALDH2 knockout in ALDH2-normal A375 cells promoted tumor growth and MAPK/ERK activation. Given the pivotal role of MAPK/ERK signaling in melanoma and cellular response to acetaldehyde, we compared A375 with ALDH2-low SK-MEL-28 and 1205Lu cells. ALDH2-low cells were intrinsically resistant to BRAF and MEK inhibitors, whereas A375 cells were not. However, A375 cells acquired resistance upon ALDH2 knockout. Furthermore, melanoma cells with acquired resistance to these inhibitors displayed further ALDH2 downregulation. Our findings indicate that ALDH2 downregulation contributes to melanoma progression and therapy resistance in BRAF-mutated human metastatic melanoma cells, highlighting ALDH2 as a potential prognostic marker and therapeutic target in metastatic melanoma. Full article

Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a severe neurodevelopmental disorder caused by a deficiency in the X-linked gene calcium/calmodulin-dependent serine protein kinase (CASK). A better understanding of the role of CASK in the pathophysiology of neurodevelopmental disorders may provide insights into novel therapeutic and diagnostic strategies for MICPCH syndrome and other neurodegenerative diseases. To investigate this, we generated CASK knockout (KO) cerebellar granule (CG) cell culture from CASK floxed (CASK^flox/flox) mice by infecting lentiviruses expressing codon-improved Cre recombinase (iCre). We performed RNA-sequencing (RNA-seq) on these cells and found that CASK-KO CG cells underwent apoptosis by activating intracellular Jun N-terminal kinase (JNK) signaling and upregulating reactive oxygen species (ROS)-related gene expression. We also performed mouse gait analysis and limb clasping behavior experiments on trans-heterozygous CASK-KO and Hprt-eGFP (CASK^+/- Hprt^eGFP/+) mice. The CASK^+/- Hprt^eGFP/+ mice exhibited cerebellar ataxic phenotypes as judged by the scores of these experiments compared to the CASK wild-type control (CASK^+/+ Hprt^eGFP/+) mice. Interestingly, the administration of the JNK inhibitor, JNK-IN-8, in CASK-KO CG cell cultures increased CG cell survival by reducing ROS generation. Moreover, injection of JNK-IN-8 into the cerebellum of CASK^+/- Hprt^eGFP/+ mice suppressed CG cell death and alleviated cerebellar ataxic phenotypes in vivo. In conclusion, JNK-IN-8 suppresses the cell death and activation of the ROS pathway in CASK-KO CG cells in both in vitro and in vivo models, suggesting its potential as a therapeutic strategy for cerebellar neurodegeneration in MICPCH syndrome. Full article

CASK-related disorders are a form of female-restricted intellectual disabilities associated with cerebellar and pontine hypoplasia. The CASK gene is regulated by X-chromosome inactivation, which results in a mosaic distribution of CASK-expressing and CASK-deficient neurons in the female brain. This mosaic distribution is believed to play a key role in the pathophysiology of X-linked neurological disorders; however, the detailed brain structure has not been extensively characterized. In this study, we used CASK heterozygous knockout (CASK-hKO) mice combined with X-linked GFP reporter mice to investigate motor abilities and the distribution of CASK-expressing cells in the brains of female CASK-hKO mice. The CASK-hKO mice exhibited motor deficits and cerebellar hypoplasia similar to those observed in patients with CASK-related disorders. Interestingly, although half of the cerebellar granule cells were CASK-negative during early postnatal development, almost all Purkinje cells and cerebellar granule cells were CASK-positive in adulthood, suggesting that CASK expression may determine the survival of cerebellar granule cells during postnatal development. We also analyzed CASK-hypomorphic mice, which express 50% less CASK than wild-type mice, and compared hemizygous males and heterozygous females. The CASK-hypomorphic heterozygous females displayed a thinner cerebellar cortex and a higher probability of CASK-positive granule cells in CASK-hKO females, suggesting that the survival of cerebellar granule cells is regulated by a combination of cell-autonomous and cell-competitive mechanisms between CASK-expressing and CASK-deficient cells, which are generated by X-chromosome inactivation. These findings provide new insights into the relationship between the mosaic distribution of cells established by X-chromosome inactivation and the pathophysiology of CASK-related disorders. Full article

Microbially induced carbonate precipitation (MICP) is the precipitation of CaCO₃ crystals, induced by microbial metabolic activities such as ureolysis. Various applications of MICP have been proposed as innovative biocementation techniques. This study aimed to verify the feasibility of ureolysis-driven MICP applications in deep-subsurface environments (e.g., enhanced oil recovery and geological carbon sequestration). To this end, we screened sludge collected from a high-temperature anaerobic digester for facultatively anaerobic thermophilic bacteria possessing ureolytic activity. Then, we examined the ureolysis-driven MICP using a representative isolate, Bacillus haynesii strain SK1, under aerobic, anoxic, and strict anaerobic conditions at 30 °C, 40 °C, and 50 °C. All cultures showed ureolysis and the formation of insoluble precipitates. Fourier transform infrared spectroscopy analysis revealed precipitates comprising CaCO₃ at 30 °C, 40 °C, and 50 °C under aerobic conditions but only at 50 °C under anoxic and strict anaerobic conditions, suggesting efficient MICP at 50 °C. Interestingly, an X-ray diffraction analysis indicated that calcium carbonate crystals that were produced under aerobic conditions were in the form of calcite, while those that were produced under anoxic and strict anaerobic conditions at 50 °C were mostly in the form of vaterite. Thus, we demonstrated ureolysis-driven MICP under high-temperature and O₂-depletion conditions, suggesting the potential of MICP applications in deep-subsurface environments. Full article

Many popular alcoholic beverages, such as Brazilian sugar cane spirit (cachaça), are aged in wood casks to achieve a smoother and more pleasant taste. The type of wood plays an important role in improving the quality of the spirit, with oak being the most widely used. Due to its elevated price and poor local availability, oak has been gradually replaced in Brazil by other woods, such as Amburana cearensis (Amburana), Cariniana legalis (Jequitibá), Hymenaea courbaril (Jatobá), and Ocotea odorifera (Cinnamon sassafras). For general purposes in beverage quality control and wood identification, and using ethanol/water extracts (cachaça 47% v/v) as a model, this article describes the construction of a low-cost electronic nose that quickly identifies the wood species that was used for aging a cachaça sample. The nose is made of an array of four chemoresistive conductive polymer gas sensors. Principal component and leave-one-out analyses showed perfect classification of all tested samples. Full article

Background and Objectives: Cutaneous melanoma (CM) poses a continuous challenge in oncology due to the developing resistance to available treatments. Doxorubicin (DOX) is noted as one of the most effective chemotherapeutics, although associated toxicity and resistance limit its use in CM treatment. Consequently, DOX has become a promising candidate for combination therapies targeting this neoplasm. Genistein (GEN) gathered significant attention due to its anti-neoplastic properties and ability to enhance the effects of DOX against several cancers, yet this association remains underexplored in CM. Therefore, this study investigated the combination therapy regimen comprising GEN and DOX in terms of anti-melanoma activity and safety profile. Materials and Methods: The in vitro experiments were performed on SK-MEL-28 and HaCaT cells. Cell viability was determined using MTT assay. Cell morphology and confluence were inspected microscopically. Nuclear and cytoskeletal aspects were assessed via immunofluorescence. Apoptosis and oxidative stress were quantified through caspase activity and intracellular reactive oxygen species (ROS) production, respectively. The irritant effect was evaluated on the chorioallantoic membrane. Results: The results revealed that the combination of GEN 10 µM with DOX (0.5 and 1 µM) provided augmented cytotoxic events (e.g., reduced cell viability, altered cell morphology and confluence, apoptotic-like impairments in nuclear shape and cytoskeletal network, increased caspases-3/7 and -9 activity, and elevated ROS) in SK-MEL-28 cells, compared to individual treatments, and exerted a strong synergistic interaction. Simultaneously, GEN 10 µM efficiently surpassed the toxic effects (e.g., viability and confluence loss, hypertrophy, and cytoskeletal condensation) of DOX (0.5 and 1 µM) in HaCaT cells. In ovo, GEN 10 µM + DOX 1 µM treatment was classified as non-irritant. Conclusions: These findings stand as one of the first contributions revealing the beneficial therapeutic interplay between GEN and DOX at physiologically achievable concentrations that resulted in elevated anti-tumor properties in CM cells and alleviated toxicity in keratinocytes. Full article

Small conductance Ca²⁺-activated K⁺ (SK) channels are expressed in atria and ventricles. However, the data on the contribution of SK channels to atrial action potential (AP) repolarization are inconsistent. We investigated the effect of SK channel modulators on AP morphology in rabbit atrial myocytes and tested the hypothesis that pharmacological activation of SK channels suppresses pacing-induced Ca²⁺ transient (CaT) and AP duration (APD) alternans. At the cellular level, alternans are observed as beat-to-beat alternations in contraction, APD, and CaT amplitude, representing a risk factor for arrhythmias, including atrial fibrillation. Our results show that SK channel inhibition by apamin did not affect atrial APD under basal conditions. However, SK channel activation by NS309 significantly shortened APD, indicating the expression of functional SK channels. Moreover, the activation of SK channels reduced CaT amplitude and sarcoplasmic reticulum Ca²⁺ load. Activation of SK channels also suppressed pacing-induced CaT and APD alternans. K_V7.1 potassium channel inhibition, simulating long QT syndrome type-1 conditions, increased the risk of atrial CaT alternans, which was abolished by the activation of SK channels. In summary, our data suggest that pharmacological modulation of SK channels can potentially reduce atrial arrhythmia risk arising from pathological APD prolongation. Full article

Aging spirits in wooden casks is a traditional and mandatory process for the production of certain products, such as whisky. The physicochemical and sensory changes that occur during aging are shaped by the characteristics of the barrels and the aging method used. In this paper, we examined the behavior of the same malt spirit when aged using two different Sherry Casks^® methods. The first one was static aging, with the distillate remaining still in the cask, and the second one was a dynamic system, characterized by the regular racking of the spirit between casks at different aging stages (Criaderas and Solera). For 36 months, the aging spirits were sampled and analyzed to determine any changes in acidity, volatile, and phenolic compound content that might indicate changes in their chemical profile. The spirits were also subjected to sensory evaluations. The analysis revealed a significant evolution of the distillate in either system, although with different chemical profiles. Multiple Linear Regression Models (MLR and PLS) were successfully used to estimate the age of the distillates at a high level of confidence. Although, after the first racking operation, the distillates in the dynamic system had an average age greater than the theoretical one, these differences tended to fade away as the system gradually stabilized. Full article

As yet, there is no systematic review focusing on benefits and issues of commercial deep learning-based auto-segmentation (DLAS) software for prostate cancer (PCa) radiation therapy (RT) planning despite that NRG Oncology has underscored such necessity. This article’s purpose is to systematically review commercial DLAS software product performances for PCa RT planning and their associated evaluation methodology. A literature search was performed with the use of electronic databases on 7 November 2024. Thirty-two articles were included as per the selection criteria. They evaluated 12 products (Carina Medical LLC INTContour (Lexington, KY, USA), Elekta AB ADMIRE (Stockholm, Sweden), Limbus AI Inc. Contour (Regina, SK, Canada), Manteia Medical Technologies Co. AccuContour (Jian Sheng, China), MIM Software Inc. Contour ProtégéAI (Cleveland, OH, USA), Mirada Medical Ltd. DLCExpert (Oxford, UK), MVision.ai Contour+ (Helsinki, Finland), Radformation Inc. AutoContour (New York, NY, USA), RaySearch Laboratories AB RayStation (Stockholm, Sweden), Siemens Healthineers AG AI-Rad Companion Organs RT, syngo.via RT Image Suite and DirectORGANS (Erlangen, Germany), Therapanacea Annotate (Paris, France), and Varian Medical Systems, Inc. Ethos (Palo Alto, CA, USA)). Their results illustrate that the DLAS products can delineate 12 organs at risk (abdominopelvic cavity, anal canal, bladder, body, cauda equina, left (L) and right (R) femurs, L and R pelvis, L and R proximal femurs, and sacrum) and four clinical target volumes (prostate, lymph nodes, prostate bed, and seminal vesicle bed) with clinically acceptable outcomes, resulting in delineation time reduction, 5.7–81.1%. Although NRG Oncology has recommended each clinical centre to perform its own DLAS product evaluation prior to clinical implementation, such evaluation seems more important for AccuContour and Ethos due to the methodological issues of the respective single studies, e.g., small dataset used, etc. Full article

Monoclonal antibody (mAb) and cell-based immunotherapies represent cutting-edge strategies for cancer treatment. However, safety concerns persist due to the potential targeting of normal cells that express reactive antigens. Therefore, it is crucial to develop cancer-specific mAbs (CasMabs) that can bind to cancer-specific antigens and exhibit antitumor activity in vivo, thereby reducing the risk of adverse effects. We previously screened mAbs targeting human epidermal growth factor receptor 2 (HER2) and successfully developed a cancer-specific anti-HER2 mAb, H₂Mab-250/H₂CasMab-2 (mouse IgG₁, kappa). In this study, we assessed both the in vitro and in vivo antitumor efficacy of the humanized H₂Mab-250 (humH₂Mab-250). Although humH₂Mab-250 showed lower reactivity to HER2-overexpressed Chinese hamster ovary-K1 (CHO/HER2) and breast cancer cell lines (BT-474 and SK-BR-3) than trastuzumab in flow cytometry, both humH₂Mab-250 and trastuzumab showed similar antibody-dependent cellular cytotoxicity (ADCC) against CHO/HER2 and the breast cancer cell lines in the presence of effector splenocytes. In addition, humH₂Mab-250 exhibited significant complement-dependent cellular cytotoxicity (CDC) in CHO/HER2 and the breast cancer cell lines compared to trastuzumab. Furthermore, humH₂Mab-250 possesses compatible in vivo antitumor effects against CHO/HER2 and breast cancer xenografts with trastuzumab. These findings highlight the distinct roles of ADCC and CDC in the antitumor effects of humH₂Mab-250 and trastuzumab and suggest a potential direction for the clinical development of humH₂Mab-250 for HER2-positive tumors. Full article

Breast Cancer (BrCa) exhibits a high phenotypic heterogeneity, leading to the emergence of aggressive clones and the development of drug resistance. Considering the BrCa heterogeneity and that metabolic reprogramming is a cancer hallmark, we selected seven BrCa cell lines with diverse subtypes to provide their comprehensive metabolome characterization: five lines commonly used (SK-Br-3, T-47D, MCF-7, MDA-MB-436, and MDA-MB-231), and two patient-derived xenografts (Hbcx39 and Hbcx9). We characterized their endometabolomes using ¹H-NMR spectroscopy. We found distinct metabolite profiles, with certain metabolites being common but differentially accumulated across the selected BrCa cell lines. High levels of glycine, lactate, glutamate, and formate, metabolites known to promote invasion and metastasis, were detected in all BrCa cells. In our experiment setting were identified unique metabolites to specific cell lines: xanthine and 2-oxoglutarate in SK-Br-3, 2-oxobutyrate in T-47D, cystathionine and glucose-1-phosphate in MCF-7, NAD⁺ in MDA-MB-436, isocitrate in MDA-MB-231, and NADP⁺ in Hbcx9. The unique and enriched metabolites enabled us to identify the metabolic pathways modulated in a cell-line-specific manner, which may represent potential candidate targets for therapeutic intervention. We believe this study may contribute to the functional characterization of BrCa cells and assist in selecting appropriate cell lines for drug-response studies. Full article

Spent nuclear fuel (SNF) from the United States’ nuclear power plants has been placed in dry cask storage systems since the 1980s. Due to the lack of a clear path for permanent geological repository for SNF, consolidated and long-term storage solutions that use durable concrete and avoid current aging and licensing challenges are becoming indispensable. Ultra-high-performance concrete (UHPC) is a rapidly growing advanced concrete solution with superior mechanical and durability properties that can help realize future resilient nuclear storage facilities. Thus, the overall goal of this review study is to demonstrate the viability of UHPC as a long-term solution for future nuclear storage facilities. The paper first identifies all possible non-nuclear (environmental) and nuclear (thermal and radiation-induced) degradation mechanisms in concrete overpacks and storage modules with critical assessment and projections on UHPC performance in comparison to current conventional concrete solutions. Next, since concrete serves as a shielding material in nuclear settings, the preliminary attenuation properties of UHPC from emerging studies are synthesized along with the possible mix modifications to improve its attenuation performance. The paper identifies the major knowledge gaps to inform future research and development, aimed at rethinking the design of SNF dry storage facilities by incorporating UHPC. Full article