— The U.S. Department of Energy’s Microreactor Program, along with Idaho National Laboratory’s development of a nuclear microreactor applications platform named MARVEL, support research and development for deploying small, transportable reactors across civilian, industrial, and defense sectors. The MARVEL microreactor, an 85-kW(thermal) fission reactor, incorporates TRIGA nuclear fuel and a sodium-potassium eutectic as its primary coolant. It is designed for safe and efficient operation using natural circulation and a low power density core. The reliance on natural circulation for primary cooling means the reactor avoids using fuel spacers to minimize core pressure drop, which could disrupt the primary coolant’s natural flow. However, the core’s tight pitch-to-rod diameter ratio of 1.056 raises the risk of fuel rod contact and elevated peak cladding temperatures. To ensure reactor safety, this study conducted computational modeling and simulations to examine the reactor’s thermal-hydraulic-mechanical characteristics, including the reactor core heat transfer coefficients, potential for rod-to-rod contact, and its impact on peak cladding temperature. The analyses indicated that the thermal deformation of the fuel rods under a worst-case scenario may lead to fuel rod contact, but peak cladding temperatures remained well below safety criteria, ensuring safe reactor operation without fuel spacers under steady-state normal operating conditions.

Intraosseous access, the fastest access in emergencies, isexclusively used for delivering medications or fluids. The correlation between intraosseous and arterial pressures remains unclear. This study aimed to explore this correlation at baseline and in various clinical scenarios (e.g., different heart rates, arrhythmias, asystolic arrest, and CPR). In 11 male Yorkshire pigs (73.4 ± 5.9kg), femoral artery and tibial Intraosseous lines were placed under anesthesia. Pressures were recorded during hemodynamic interventions and cardiac arrest. Analyses included Pearson's r, Wilcoxon rank-sum test, and BVAR. Intraosseous pressure showed correlating pulsatility with arterial pressure, ranging from 9 to 71% of mean arterial pressure. Correlation was strong under normal conditions (r = 0.75-0.96, p < 0.001) and during CPR (r = 0.65-0.99, p < 0.001), weakened during asystole (r = 0.26 ± 0.46, p < 0.001), and wasdisrupted by epinephrine (r = 0.04, p < 0.001). Asystole was identifiable on intraosseous tracings. Intraosseous pressure effectively reflects circulatory activity and may aid in accurately identifying asystole with possible clinical implications for CPR.

Abstract We investigate certain immersions of constant curvature from Riemann surfaces into flag manifolds equipped with invariant metrics, namely primitive lifts associated to pseudoholomorphic maps of surfaces into complex Grassmannians. We prove that a primitive immersion from the two-sphere into the full flag manifold which has constant curvature with respect to at least one invariant metric is unitarily equivalent to the primitive lift of a Veronese map, hence it has constant curvature with respect to all invariant metrics. We prove a partial generalization of this result to the case where the domain is a general simply connected Riemann surface. On the way, we consider the problem of finding the invariant metric on the flag manifold, under a certain normalization condition, that maximizes the induced area of the two-sphere by a given primitive immersion.

ABSTRACT Objectives Reperfusion, an essential therapeutic strategy for salvaging ischemic myocardium in ischemic heart disease, paradoxically exacerbates myocardial injury. Ferroptosis is a pivotal mechanism underlying myocardial ischemia-reperfusion injury (MIRI). Nrf2 can regulate ferroptosis, which could undergo SUMOylation at lysine 110 (K110) and was subsequently de-SUMOylated by Senp1. This study aimed to determine whether Nrf2 de-SUMOylation could mitigate MIRI by inhibiting myocardial ferroptosis. Methods Nrf2 K110R mice, mimicking Nrf2 de-SUMOylation, were generated. Mice cardiac morphology and function were observed by hematoxylin–eosin staining (HE) and echocardiography under normal and MIRI conditions. Ferroptosis inhibitor liproxstatin-1 (Lip-1) was used to demonstrate ferroptosis participation in Nrf2 de-SUMOylation regulated MIRI. In vitro, SUMO1/sentrin-specific protease 1 Senp1 KO H9C2 cells were subjected to RSL3-induced ferroptosis to explore underlying mechanism. Results Nrf2 K110R mice showed normal cardiac morphology and function at baseline. However, de-SUMOylation of Nrf2 alleviated myocardial ferroptosis, resulting in a reduction of MIRI severity in MIRI mice. The administration of Lip-1 attenuated the differences in MIRI between Nrf2 wild-type and K110R mice. Mechanistically, Nrf2 de-SUMOylation was associated with a reduction in Transferrin receptor (Tfr) expression level, thereby mitigating ferroptosis in cardiomyocytes. Conclusion This study highlighted the role of Nrf2 SUMOylation in promoting ferroptosis during MIRI and identified Nrf2 de-SUMOylation as a potential therapeutic target for MIRI.

Abstract As a critical component of railway transportation systems, the turnout plays a key role in ensuring the safety of train operations and enhancing transport efficiency. The current signal of a turnout provides critical insight for identifying anomalies and exhibits distinct stage characteristics during its operation. To automatically identify these stages for equipment condition monitoring as well as intelligent operation and maintenance, accurate boundary detection is indispensable. Thus, this paper proposes a keypoint-guided stage segmentation approach for current curve images of railway turnout system. The method performs stage segmentation using solely the top-left keypoint of each region, with adjacent keypoints defining stage boundaries, dramatically reducing model complexity. To enhance boundary supervision, an anisotropic Gaussian kernel is introduced during feature map generation, and a Sobel-based auxiliary gradient constraint is incorporated to improve detection precision. Furthermore, a temporal continuity constraint is applied in the post-processing stage to ensure logical consistency between consecutive segments. Experimental results demonstrate the robust performance of the proposed method, achieving precise segmentation of turnout current-curve images under both normal and abnormal conditions. Furthermore, it maintains low computational cost and ensures the rationality of the detection results.

Introduction This experimental study aims investigates the gene expression plasticity of free-living infective third-stage larvae (L3) of Anisakis simplex in response to extreme thermal stress, potentially linked to the increasing occurrence of climate change-induced marine heatwaves. Methods Using an RNA-seq approach, the molecular transcriptomic responses of L3 larvae were analyzed under both normal (15 °C) and extreme (28 °C) heating aquarium conditions environmental stress. Data were collected from90 viable L3 in good condition, sampled from viscera of fresh European hake ( Merluccius merluccius ), and subjected to a seawater survival assay simulating the most extreme ocean warming event currently recorded whitin the Spanish Marine Demarcation. A bioinformatic pipeline involving read alignment (STAR), differential expression (DESeq2), and gene ontology enrichment was applied. Results The analysis revealed that larvae remained viable for up to 60 days at 15 °C but only a week at 28 °C. Transcriptomic data showed from 241 to 244 DEGs depending on each comparison, with a progressive downregulation of cuticle-related genes, a strong upregulation of peptidases, and coordinated neural modulation; with reduced ion channel activity and enhanced expression of key neurotransmission-related genes. Additionally, there was strong upregulation of genes involved in glycogen degradation and galactose metabolism, along with consistent downregulation of glycolysis-related genes. Discussion The transcriptomic patterns describe above indicate that short-term marine heatwave conditions (28 °C) severely compromise viability of free L3 of A. simplex, which clearly prioritize survival processes while suppressing developmental pathways. These findings suggest that the more intense, longer-lasting, and widespread marine heatwaves observed along the Spanish marine demarcation over the last 15 years may influence parasite persistence and transmission of infective stages to paratenic fish host. This highlights the One Health significance of such adaptative response, particularly regarding parasite biogeographical dispersion and associated zoonotic risk.

Since the discovery of gadolinium (Gd) in the brain following the administration of gadolinium-based contrast agents (GBCAs), considerable progress has been made in understanding their pharmacokinetics and neurotoxicology. This review summarizes animal studies assessing the presence of Gd after GBCA administration, with a specific focus on functional and behavioral outcomes, rather than providing a comprehensive overview of all aspects of Gd presence in the brain. These findings indicate that Gd accumulation in the brain depends on the chemical structure of GBCAs, with linear agents exhibiting greater retention and slower clearance than macrocyclic agents. Gd distribution is nonhomogeneous, primarily localized in deep gray matter structures, and is influenced by cerebrospinal fluid-mediated transport and perivascular deposition. Although motor and cognitive functions are generally unaffected under normal conditions, prolonged exposure to linear GBCAs or preexisting conditions such as inflammation or metabolic disorders may increase neurotoxic risks, resulting in motor and cognitive deficits. Pain and sensory hypersensitivity are frequently and reproducibly observed, particularly when linear agents are used. We will also discuss the potential mechanisms of neurotoxicity caused by free Gd3+ ion. However, these mechanistic findings are limited because the studies cannot be extrapolated to clinical practice. Future studies should investigate the potential associations between GBCA exposure and neurodegenerative diseases. These insights are essential for enhancing GBCA safety and informing clinical guidelines.

Purpose: This study aimed to quantify the severity of fear of falling (FOF) in people with low vision (LV) compared with age–gender-matched healthy individuals during gait initiation (GI). Methods: A total of 14 adults with LV and 14 age–gender-matched healthy adults were recruited from local communities. The Falls Efficacy Scale International was used to evaluate FOF. We compared temporal events between healthy and LV groups. For the healthy group, GI under normal vision was further compared to conditions using a low-vision sight simulator (SS) and an immersive virtual reality (VR) environment designed to simulate a fear-evoking experience. Independent t-test and one-way repeated measure ANOVA were conducted for statistical analysis (p &lt; 0.05). Results: People with LV showed a significantly greater FOF than healthy individuals (p &lt; 0.05). During GI, participants with LV exhibited significantly prolonged anticipatory postural adjustment (APA) durations compared to healthy normal and SS conditions (p &lt; 0.05). While VR-evoked fear in healthy participants primarily prolonged the push-off (PO) phase, the delay in the LV group was characterized by a significantly extended initial anticipation (AP) phase. Notably, the APA duration in the LV group showed no significant difference compared to the healthy VR condition, indicating that the inherent fear in LV produces postural delays as severe as those induced by extreme VR-evoked fear of heights (p &gt; 0.05). Conclusions: This study demonstrates that individuals with LV adopt a chronically conservative motor program during the transition from standing to walking. These postural hesitations are statistically comparable to those observed under fear-evoking, VR-induced environments. These findings suggest that LV is associated with a distinct biomechanical strategy that prioritizes static stability over dynamic movement. Accordingly, multidisciplinary rehabilitation approaches that emphasize sensory reweighting, including vestibular training, alongside interventions targeting FOF, may be essential for mitigating altered postural control and reducing fall risk in the LV population.

Diabetic patients are particularly vulnerable to heat exposure due to impaired thermoregulation and reduced sweating ability. The impact of heat on skin cell function, particularly keratinocytes, is poorly understood. Recent studies highlight the critical role of nitric oxide (NO) in thermoregulation and heat stress responses, but its specific involvement in keratinocyte responses and metabolic profiles remains unexplored. This proof-of-concept study investigates the metabolic profiles of HaCat keratinocytes under normal and high-glucose conditions during varied heat exposures. We conducted experiments using a metabolomics approach, NO levels assessments, western blot analysis, and evaluations of mitochondrial morphology. Our findings indicate that acute heat exposure over 90 minutes significantly alters metabolic pathways, particularly amino acid metabolism (including arginine, valine, leucine, and serine), the pyrimidine metabolite uracil, and glycolysis, notably lactate production. Arginine metabolism was uniquely affected by high glucose combined with heat, aligning with previous clinical observations. Furthermore, we discovered that changes in NO production correlated with heat exposure duration, and that NO levels in extracellular vesicles (EVs) from HaCat cells were inversely related to intracellular NO levels. Additionally, we observed alterations in HSP-70 protein expression and mitochondrial morphology, supporting cellular adaptation to thermal stress. This study is the first to demonstrate heat-induced metabolic changes in keratinocytes involving arginine and NO, highlighting their potential as clinical biomarkers for thermal stress adaptation, with implications for both healthy individuals and diabetic patients.

Visual input supports locomotion through sensorimotor integration. However, the neural mechanisms underlying how the brain adapts to degraded vision are not well understood. This study investigated the effects of visual occlusion on interactions between regions within the sensorimotor network. Twelve healthy young adults (8 males, 4 females; mean age 24.0 ±2.1 years) were recruited from the Department of Ophthalmology at Peking University Third Hospital between December 2024 and September 2025. Pattern-reversal visual evoked potentials were recorded under both normal vision and visual occlusion condition (Snellen 20/60 acuity). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data to calculate the amplitude of low-frequency fluctuations (ALFF) and seed-based functional connectivity (FC) focused on visuomotor integration regions. A one-way repeated-measures analysis of variance was conducted with three within-subject conditions: seated rest, level walking with normal vision, and level walking with visual occlusion. Stimuli consisted of checkerboard patterns with large (1°) and small (15') checks. Under 1° visual stimulation, visual occlusion prolonged binocular P100 latency (117.00 ± 8.55 ms vs. 111.81 ± 5.12 ms; 116.78 ± 9.79 ms vs. 110.96 ± 4.28 ms; all P <0.05) and reduced N75-P100 amplitude (5.798 ± 2.372 μV vs. 8.613 ± 3.949 μV; 6.230 ± 2.459 μV vs. 7.453 ± 2.692 μV, all P <0.05). For 15' stimulation, occlusion decreased both binocular N75-P100 (5.935 ± 3.500 μV vs. 10.794 ± 5.249 μV; 3.991 ± 1.585 μV vs. 10.361 ± 3.143 μV, all P <0.001) and P100-N135 amplitudes (6.218 ± 3.516 μV vs. 12.499 ± 4.236 μV; 4.427 ± 2.218 μV vs. 10.767 ± 4.904 μV, all P <0.001). Rs-fMRI analysis showed reduced ALFF in the right paracentral lobule after walking (peak Montreal Neurological Institute (MNI) coordinates: 3, -39, 66; P <0.001, F = 14.009). Walking activated multiple visuomotor pathways (all P <0.001), including the bilateral calcarine and middle temporal gyri, the right calcarine and middle frontal gyri, the bilateral supplementary motor area and right cuneus, and the bilateral precentral gyrus and right cerebellar lobule VI. The visual occlusion strengthened FC between the right precentral and the right middle frontal gyri (peak MNI: 27, 57, 27; F = 16.456, P <0.001). Basic visuomotor pathways demonstrate consistent activation to maintain locomotion. Increased functional connectivity between the right precentral and middle frontal gyri serves as a compensatory mechanism for reduced visual input.

Transient receptor potential vanilloid 6 (TRPV6) is a highly Ca2+-permeable cation channel predominantly expressed in the intestinal epithelium. It plays a crucial role in maintaining systemic calcium homeostasis by regulating Ca2+ absorption in the intestine. However, its local physiological and pathophysiological roles in the intestine remain unexplored. The exact cause of inflammatory bowel disease is not fully understood; however, disruption of the intestinal epithelial barrier is a key pathogenic mechanism. In this study, we aimed to elucidate the role of TRPV6 in the pathogenesis of colitis. Experimental colitis was induced in TRPV6-deficient (KO) and wild-type (WT) mice by administering 2% dextran sulfate sodium solution (DSS) in drinking water for 7 days. DSS treatment resulted in weight loss, diarrhea/bloody stool, histological colonic injury, and colon shortening. The systemic symptoms and colonic injury were significantly worse in TRPV6KO mice than in WT mice. DSS treatment increased tumor necrotic factor-α, interleukin-1β, interleukin-6 mRNA expressions, and myeloperoxidase activity, and these responses were significantly enhanced in TRPV6KO mice compared with WT mice. Under normal (no-DSS-treated) conditions, TRPV6KO mice exhibited increased intestinal permeability compared with WT mice. No difference was observed in the number of goblet cells between WT and TRPV6KO mice; however, the expression of intercellular junction proteins, including E-cadherin, claudin-3, and occludin, was significantly suppressed in TRPV6KO mice compared with WT mice. These findings suggest that TRPV6 protects against DSS-induced colitis, potentially by regulating epithelial barrier function through intracellular junction protein expressions.

Cotton (Gossypium hirsutum L.) yield is threatened by heat stress that impair pollen development and reduce reproductive success. This study aimed to identify tolerant genotypes by integrating physiological screening with molecular analysis of key pollen development genes. Twenty cotton genotypes were evaluated in a randomized complete block design (RCBD) with three replicates at the research area of MNS-University of Agriculture Multan under normal and heat stress conditions for two consecutive years. Physiological parameters including 2,3,5 triphenyl-tetrazolium chloride (TTC), acetocarmine-based pollen viability and relative cell membrane thermo-stability were measured to assess heat tolerance and sensitive genotypes. Heat tolerant genotypes including UAM-20, FH-492, MNH-1035 and Cyto-177 exhibited higher pollen viability and reduced cell membrane injury under heat stress. Whereas, FH-901, CIM-448, JS-212 and CRIS-5A were identified as heat sensitive genotypes due to low pollen viability and higher cell membrane injury. Expression analysis of GhADF7 and GhFLA14 through RT-PCR demonstrated differential expression between heat tolerant and sensitive genotypes. Tolerant genotypes showed higher expression of both genes under heat stress as compared to the sensitive genotypes. These results suggest that integration of physiological screening and gene expression profiling provides a reliable approach to screen heat tolerant genotypes and highlights GhADF7 and GhFLA14 as key factors enabling reproductive thermotolerance.

Autophagy is a highly conserved, intracellular recycling process by which cytoplasmic contents are degraded in the lysosome. This process occurs at a low level constitutively; however, it is induced robustly in response to stressors, in particular, starvation of critical nutrients such as amino acids and glucose. That said, the relative contribution of these inputs is ambiguous, and many starvation medias are poorly defined or devoid of multiple nutrients. Here, we set out to create a quantitative dataset of autophagy across multiple stages in single, living cells, measured under normal growth conditions and during nutrient starvation of amino acids or glucose. We found that autophagy is induced by starvation of amino acids, but not glucose, in U2OS cells, and that MTORC1-mediated ULK1 regulation and autophagy are tightly linked to amino acid levels. While autophagy is engaged immediately during amino acid starvation, a heightened response occurs during a period marked by transcriptional upregulation of autophagy genes during sustained starvation. Finally, we demonstrated that cells immediately return to their initial, low-autophagy state when nutrients are restored, highlighting the dynamic relationship between autophagy and environmental conditions.

Cancer is the second leading cause of death in both developed and developing countries. In cancer cells, hemostasis is disrupted, a process that is maintained under normal conditions in healthy cells. Transcription factors that play a crucial role in preserving this hemostasis have been linked to cancer. In recent years, the involvement of proteins from the FOX transcription factor family in cancer development has been extensively studied, highlighting their potential relevance for therapeutic research. Although one of these proteins, Forkhead Box K2 (FOXK2), was identified in the early 1990s, its biological functions in cellular processes remain incompletely understood. Research has highlighted the roles of FOXK2 in critical molecular processes, including de novo nucleotide synthesis, the expression of metabolic-related enzymes, DNA mismatch repair, cell proliferation, differentiation, apoptosis, and autophagy. Furthermore, it has been shown that FOXK2 mediates the binding of transcription factors that do not directly interact with methylated DNA to methylated regions, and also influences the DNA methylation process. Studies investigating its role in cancer indicate that FOXK2 functions as an oncogenic in certain tissues while acting as a tumor suppressor in others. The role of FOXK2 is particularly controversial, especially in hormone-dependent diseases. In this review, the roles of FOXK2 in various cancer cell types were analysed. Additionally, Gene Ontology (GO) enrichment analyses of miRNAs targeting FOXK2 were conducted, highlighting aspects of FOXK2 that have yet to be explored. GO analysis revealed that miRNAs targeting FOXK2 are particularly involved in regulatory processes. In conclusion, FOXK2 may represent a potential therapeutic target in certain cancer types, although its context-dependent roles require further investigation.

Crop quality arises from the interplay of genetics and environment. While moderate salt stress is known to enhance fruit sweetness, the underlying molecular mechanisms remain unclear. Using tomato (Solanum lycopersicum) as a model, this study investigates how salt stress promotes fruit sugar accumulation. Root-derived abscisic acid (ABA) transport to fruit acts as the key signal under salt stress. Elevated fruit-ABA activates the kinase SlSnRK2.6, which phosphorylates the SlZHD8 transcription factor. This phosphorylation inhibits SlZHD8 function by reducing its protein stability and DNA-binding, thereby relieving its repression of SlSUS3 and SlSWEET12 to enhance fruit-sugar accumulation. Furthermore, the SlSnRK2.6-SlZHD8-SlSWEET12 module also regulates root-sugar accumulation and confers salt tolerance. Evolutionary analysis revealed a beneficial ZHD8 haplotype, whose reduced promoter-binding affinity promotes fruit-sugar accumulation under normal conditions and enhances salt tolerance. These findings explain how stress enhances quality and highlight the potential of key mutations of ZHD8, particularly the beneficial haplotype, for breeding tomatoes with improved sugar content and salt tolerance.

Ribonucleases are associated with processing and degradation of diverse RNA substrates. These enzymes act on the substrate with high specificity, often in association with their interacting partners. Functionally redundant exoribonucleases are indispensable for maintaining the physiological homeostasis under normal and challenging conditions for growth. In this review article, we will report the comprehensive role of exoribonucleases in RNA metabolism especially the processing, maturation and degradation. Structural aspects of exonucleases, tendency to oligomerize, and their association with other cellular proteins that facilitate their interaction with RNA substrate and modulate their activity have also been highlighted. Transcription and post-transcriptional regulatory mechanisms of gene expression that are crucial for maintaining levels of exoribonuclease expression has been briefly discussed.

Extreme weather can cause urban groundwater levels (GWLs) to rise sharply, making anti-uplift performance critical for underground structures. We present a drainage-pressure relief anti-uplift technique (DPRAT) that integrates the Dupuit circular island model, the Thiem equation, and GWL distribution assumptions into an intelligent control system. The system activates automatically when the measured water head exceeds a design threshold, draining groundwater to relieve hydrostatic pressure on buried structures. Tests and simulations in Chengdu's expansive soil areas confirm that anti-uplift failure results primarily from buoyant forces and soil expansion. To ensure adequate safety margins, the target drainage level is calibrated to maintain system inactivity approximately 80% of the time under normal conditions. Four years of field monitoring demonstrate that DPRAT effectively maintains GWLs below the design datum during extreme rainfall events. A 50-year life cycle assessment reveals that DPRAT reduces cradle-to-grave carbon emissions by up to 97.5% compared with conventional uplift anchors, representing a substantial shift from high-energy construction methods to low-carbon alternatives.

Impact of fluoride on antioxidant activity and mitochondrial homeostasis in fetal rat kidney.

Orthogonal biosimilarity testing of etanercept: A green and white analytical approach.

The involvement of Na,K-ATPase enzyme in the development of Alzheimer's disease.