Search Results (1,263)

Ferritic/martensitic (F/M) steel is a candidate material for key structures in fourth-generation nuclear energy systems (such as fusion reactors and fast reactors). Irradiation hardening behavior is a core index to evaluate the material’s stable performance in a high-neutron-irradiation environment. In this study, based on 2048 composition and property data, a correlation model between key elements and their interactions and irradiation hardening in F/M steel was constructed using a Bayesian optimization neural network, which realized quantitative prediction of the effect of composition on hardening behavior. Studies have shown that the addition of about 9.0% Cr, about 0.8% Si, Mo content higher than about 0.25%, and the addition of Ti, Mn can effectively suppress the irradiation hardening of F/M steel, while the addition of N, Ta, and C will aggravate its irradiation hardening, and the addition of W and V has little effect on the irradiation hardening of F/M steel. There is an interaction between the two elements. C-Cr has a strong synergistic mechanism, which will cause serious hardening when the content is higher than 0.05% and the Cr content is higher than 10%. Cr-Si has a strong antagonistic mechanism, which can achieve the comprehensive irradiation hardening effect in the 9Cr-0.8Si combination. N-Mn needs N controlled lower than 0.01%. Mo-W needs to control Mo content higher than 0.5% to alleviate irradiation hardening. There is a weak synergistic effect in Si-V; when the content is between 0.3% and 0.8% and the V content is between 0.2% and 0.3%, it can assist in optimizing the composition of F/M steel. Through the optimization of multi-element combination, the composition of F/M steel with lower irradiation hardening can be designed. Full article

The creatinine-to-cystatin C ratio (CCR), a surrogate for skeletal muscle mass, may also be associated with liver fibrosis due to the strong link between sarcopenia and liver disease progression. We aimed to evaluate the utility of CCR as a noninvasive marker of liver fibrosis in metabolic-dysfunction-associated steatotic liver disease (MASLD). This retrospective study included 104 patients with biopsy-proven MASLD. CCR was calculated using serum creatinine and cystatin C levels. Liver fibrosis was staged histologically (F0–F4), and skeletal muscle mass was assessed using the skeletal muscle index (SMI) on computed tomography. Associations between CCR and liver fibrosis, SMI, and nonalcoholic fatty liver disease activity score were analyzed. ROC analysis evaluated CCR performance alone and in combination with FIB-4 and enhanced liver fibrosis (ELF) scores. CCR values were significantly lower in patients with significant fibrosis (≥F2). The AUROC of CCR for detecting ≥F2 fibrosis was 0.621 (95% CI: 0.509–0.733), with an optimal cutoff of 0.664. CCR alone yielded an AUC of 0.815 for predicting ≥F2 fibrosis. Combining CCR with FIB-4 and ELF substantially improved diagnostic accuracy, increasing the AUROC from 0.621 (CCR alone) to 0.820 for the combined model. CCR correlated positively with SMI (r = 0.451, p < 0.001). CCR is a simple, cost-effective biomarker reflecting muscle mass and liver fibrosis in MASLD. Combining CCR with established markers may enhance risk stratification and reduce the need for liver biopsy in selected cases. Full article

This study presents a prism-based self-referencing digital holographic microscopy (PSDHM) system that utilizes a wedge prism. The front and rear surfaces of the prism have a wedge angle of 2°, which can reflect the parallel incident light, respectively, to generate a lateral displacement that varies with the propagation distance of the optical path. Focusing on the quantitative analysis of droplets, this innovative system effectively images water droplets and their dynamic evaporation processes. Results show that the evaporation process of water droplets undergoes three stages, each stage corresponding to a theoretical model. These are the constant contact radius (CCR) mode, the stick-slip (SS) mode, and the stick-jump (SJ) mode. Furthermore, by comprehensively analyzing the contact angle and the specific morphology of the droplet’s contact area, we revealed that the hydrophilicity of the cover glass influences the droplet morphology, contact area, and the evaporation process. Full article

Metastatic spread remains the primary cause of mortality in melanoma. Our aim was to investigate the role of dermal endothelial cells in modulating melanoma cell invasiveness and cytokine/chemokine pattern. Primary melanoma cell lines were co-cultured with human dermal endothelial cells and assessed using Matrigel invasion assays. Invasive and non-invasive subpopulations were separated for gene expression analyses, and candidate molecules were further evaluated in patient tissue and plasma samples. Co-culture of melanoma and dermal endothelial cells revealed altered expression of several cytokine receptor genes (CCR5, CXCR7, IL1RAPL2, IL4R, IL6ST, IL18R1, IL22RA2, TNFRSF10A, TNFRSF11B, and TNFRSF21). Analysis of clinical melanoma samples showed significant downregulation of IL1RAPL2 and TNFRSF10A in cutaneous metastases, whereas IL6ST expression correlated with Breslow thickness of the primary tumor rather than metastatic site. Proteome profiling of dermal endothelial cells revealed alterations in Midkine, GROα, MIP-3α, IL-8, and SDF-1 following co-culture with melanoma cells. Plasma measurements in melanoma patients confirmed elevated Midkine levels in skin metastases and decreased MIP-3α in metastatic disease. These results highlight potential cytokine and chemokine-mediated pathways involved in melanoma dermal invasion and cutaneous metastasis. While some findings did not reach statistical significance, concordant trends between in vitro and patient-derived data suggest their relevance and warrant further investigation in larger cohorts. Full article

Mitochondria possess their own genome, which encodes subunits of the electron transport chain, rendering mitochondrial protein translation essential for cellular energy metabolism. Mitochondrial dysfunction affects nuclear transcription through the retrograde response. We applied RNA-seq to investigate whether and how the inhibition of mitochondrial translation by chloramphenicol (CAP) affects transcriptome regulation in proliferating or stationary-phase cells of Schizosaccharomyces pombe growing in fermentative or respiratory media. Stationary-phase cells in glucose medium exhibited the strongest transcriptome response to CAP, characterized by expression signatures similar to those observed under other stresses, including the retrograde response. The induced genes were also significantly enriched in cytoplasmic carbon metabolism pathways, reflecting a transcriptional reprogramming from respiration to fermentation. The transcription factors Scr1 and Rst2, regulators of carbon catabolite repression (CCR), controlled a common set of carbon metabolism genes in CAP-treated stationary-phase cells, and they showed opposing effects on the lifespan of these cells. Rst2 was required for the induction of carbon metabolism genes and maintained nuclear localization in CAP-treated stationary-phase cells. A systematic genetic interaction screen revealed functional relationships of Rst2 with processes related to stress and starvation responses. These findings uncover a complex transcriptional program in stationary-phase cells that adapt to inhibited mitochondrial translation, including stress- and retrograde-like responses, contributions of the CCR factors Scr1 and Rst2, and adjustment of carbon metabolism to deal with mitochondrial dysfunction. Full article

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. We have previously shown that Depo-Provera administration increases immune markers for HIV preference on peripheral and cervical CD4⁺ T cells but decreases the levels of most immune mediators at vaginal and cervical mucosa. In this study, we determined the effect of cervicovaginal secretions from women before (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment on HIV infectivity ex vivo. The effect of supernatants from vaginal, endocervical, and rectal swabs and from cervical cytobrush on HIV infectivity were assessed by a single-cycle infection assay using CCR5-using HIV-luciferase reporter viruses. We found that endocervical secretions from women after Depo-Provera treatment promoted HIV infectivity. When analyzing the association between endocervical mediator changes in response to Depo-Provera, available in our previous study, and the changes in HIV infectivity pre- and post-treatment, we found that changes in IL-17 and VEGF were positively associated with changes in HIV infectivity at visit 2 compared with visit 1, whereas changes in RANTES and IL-4 were negatively associated with HIV infectivity. The negative association between RANTES and HIV infectivity was also observed at visit 3 compared with visit 1. Additionally, changes in IL-1α at visit 3 were positively associated with changes in HIV infectivity compared with visit 1. These findings suggest that Depo-Provera may increase the HIV risk by shifting the mucosal milieu that promotes HIV infectivity. Full article

This study examines the long-run relationship between carbon dioxide (CO₂) emissions and key macroeconomic and sectoral drivers in ten ASEAN economies from 1995 to 2023. Employing Driscoll–Kraay standard errors, Prais–Winsten regression, heteroskedastic panel-corrected standard errors, Fully Modified Ordinary Least Squares (FMOLS), Dynamic Ordinary Least Squares (DOLS), and Canonical Cointegrating Regression (CCR) estimators, the analysis accounts for cross-sectional dependence, slope heterogeneity, and endogeneity. Results indicate that GDP exerts a more-than-unitary positive effect on emissions, with a negative GDP-squared term supporting the Environmental Kuznets Curve. Agriculture raises emissions through land-use change and high-emission cultivation practices, while tourism shows a negative association likely reflecting territorial accounting effects. Trade openness increases emissions, highlighting the carbon intensity of export structures, whereas foreign direct investment exerts no significant net effect. These results suggest that ASEAN economies must accelerate renewable energy adoption, promote climate-smart agriculture, embed enforceable environmental provisions in trade policy, and implement rigorous sustainability screening for FDI to achieve low-carbon growth trajectories. Full article

In the context of China’s “double carbon” goals, examining the spatial–temporal characteristics and influencing factors of the synergistic effect of pollution control and carbon reduction (SEPCR) in the Chengdu–Chongqing region (CCR) is crucial for advancing both air pollution (AP) control and carbon emissions (CE) mitigation. This study uses data on AP and CE from 2007 to 2022 and employs the coupling coordination degree (CCD) model, spatial autocorrelation analysis, and kernel density estimation to investigate the spatial–temporal distribution and dynamic evolution of the CCD between AP and CE in the CCR. Additionally, the Tobit regression model is applied to identify the key factors influencing this synergy. The results indicate that (1) during the study period, the air pollutant equivalents (APE) in the CCR showed a declining trend, while CE continued to increase; (2) the overall level of coupling coordination remained low, exhibiting an evolutionary pattern of initial increase, subsequent decrease, and then recovery, with synergistic effects showing slight improvement but significant fluctuations; (3) the SEPCR in the CCR was generally dispersed, exhibiting no significant spatial autocorrelation. A “core–periphery” structure emerged, with Chongqing and Chengdu as the core and peripheral cities forming low-value zones. Low–low clusters indicative of a “synergy poverty trap” also appeared; (4) economic development (PGDP), openness level (OP), and environmental regulation intensity (ER) are significant positive drivers, while urbanization rate (UR), industrial structure upgrading (IS), and energy consumption intensity (EI) exert significant negative impacts. Full article

Glioblastoma (GBM) is an aggressive brain tumor with a highly immunosuppressive microenvironment that promotes tumor progression and therapy resistance. Tumor-associated macrophages (TAMs), comprising up to 50% of the tumor mass, are recruited via chemokine axes such as CCL2/CCR2, CX3CL1/CX3CR1, and CXCL12/CXCR4 and adopt an M2-like immunosuppressive phenotype, facilitating immune escape and angiogenesis. Key signaling pathways, including CSF1R, STAT3, NF-κB, PI3K/Akt, and HIF-1α, regulate TAM function, making them promising therapeutic targets. Strategies such as TAM depletion, reprogramming, and immune checkpoint blockade (PD-1/PD-L1, and CD47-SIRPα) have shown potential in preclinical models. Emerging approaches, including CAR-macrophage (CAR-M) therapy, nanotechnology-based drug delivery, and exosome-mediated modulation, offer new avenues for intervention. However, clinical translation remains challenging due to GBM’s heterogeneity and adaptive resistance mechanisms. Future research should integrate multi-omics profiling and AI-driven drug discovery to refine TAM-targeted therapies and improve patient outcomes. This review provides a comprehensive analysis of TAM-mediated immune regulation in GBM and explores evolving therapeutic strategies aimed at overcoming its treatment barriers. Full article

Electroacupuncture (EA) has shown analgesic potential for neuropathic pain, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether EA relieves neuropathic pain by modulating CCL2/CCR2 signaling and microglial activation in the spinal cord. Neuropathic pain was induced in rats by L5 spinal nerve ligation. EA was administered at acupoints ST36 and GB34 (1 mA, 2 Hz, 30 min) daily from postoperative days 3 to 7. Rats were assigned to anesthetized control (ANE), non-acupoint stimulation (NAP), and acupoint stimulation (ACU) groups. Pain behavior was evaluated using paw withdrawal threshold and latency. Western blot and immunofluorescence were used to assess CCL2, CCR2, Iba1, IL-1β, and TNF-α expression in the L4–L6 spinal cord. EA significantly attenuated mechanical allodynia and thermal hyperalgesia in the ACU group, accompanied by reductions in CCL2, CCR2, microglial marker Iba1, and pro-inflammatory cytokines. Most importantly, intrathecal administration of recombinant CCL2 completely abolished EA’s analgesic effects, establishing the causal necessity of CCL2/CCR2 signaling in EA-mediated analgesia. These findings suggest that EA exerts its analgesic effects through downregulation of the CCL2/CCR2 pathway and inhibition of microglial activation. The reversal of EA’s effects by exogenous CCL2 supports the critical role of spinal chemokine signaling in EA-mediated analgesia. Full article

Global cerebral hypoxia triggers (mal-)adaptive responses that can lead to neuronal damage. This study evaluated edaravone’s neuroprotective effects in a rat hypoxia model, focusing on sex differences, treatment durations, and behavioral outcomes. Male and female rats underwent global cerebral hypoxia induced by rocuronium, with post-hypoxia edaravone treatment. Motor coordination and activity were assessed through exploratory behavior tests. Histological analyses evaluated neuronal integrity and apoptosis, while microglial activity and gene expression were analyzed via immunofluorescence and qPCR. Edaravone showed transient neuroprotective effects on motor behavior and early immune responses, particularly in the cerebellum and hippocampus. No gross morphological damage was observed, though functional impairments occurred despite preserved cytoarchitecture. Microglial activity was initially suppressed in treated and later activated in untreated hypoxic brains, suggesting modulating immune responses. Gene expression analysis revealed region-specific, time-dependent, and sex-specific changes, including early upregulation of CCR7, S100B, and NSE in treated animals. Males were more susceptible to hypoxic damage, while females showed higher baseline resistance and better functional recovery. Seven-day edaravone treatment increased apoptotic markers in male cerebellum, indicating sex-specific differences in cell death mechanisms. These findings highlight the potential for personalized therapy and underscore the importance of considering sex differences in both research and clinical practice. Full article

We investigate the key factors that shape the dynamic evolution of Day-Ahead spot prices of seven European interconnected electricity markets of the Core Capacity Calculation Region, Core CCR (Austria AT, Hungary HU, Slovenia SI, Romania RO), the Southeast CCR (Bulgaria BG, Greece GR) and the Greece-Italy CCR (GRIT CCR), with emphasis on price surges and discrepancies observed in SEE CCR markets, during the period 2022–2024. The high differences in the prices of the two groups have generated political reactions from the countries that ‘suffer’ from these price discrepancies. By applying Machine Learning (ML) approaches, as Markov Blanket (MB) and Local, causal structures learning (LCSL), we are able of ‘revealing’ the entire path of volatility spillover of both spot price and the Cross-Border Transfer Availabilities (CBTA) between the countries involved, from north to south, thus uncovering i.e., ‘lifting the blanket’, to discover the ‘true’ structure’ of the path of causalities, responsible for the price disparity. The above methods are supported by the ‘mainstream’ approach of computing the correlation of the spot price and CBTA’s volatility curves of all markets, to detect volatility spillover effects across markets. The main findings of this hybrid approach are (a) the volatility of some Core CCRs (AT, HU, RO) markets’ spot price and CBTAs with neighboring countries, ‘uncovered’ to be pivotal, operating as a ‘transmitter’ of volatility ‘disturbances’, over its entire connection and causal path from Core CCR to SEE CCR markets, partially contributing to their price surge, (b) reduced available capacity for cross-border trading of some Core and SEE CCRs (they have not satisfied the minimum 70% requirement margin available for cross-zonal trade, MACZT), combined with local weather and geopolitical conditions, could have exacerbated the impact of the Flow-based Market coupling method (FBMC) used in the Core CCRs, on the prices’ surge of SEE CCR’s countries, e.g., via induced non-intuitive flows. This phenomenon questions the efficiency and reliability of the European Target’s model (TM) in securing ‘homogeneous’ power prices across all interconnected markets, core and peripheral. Full article

Complex chromosomal rearrangements (CCRs) are rare structural abnormalities involving at least three chromosomal breakpoints and often two or more chromosomes. Owing to their inherent genomic complexity, CCRs are frequently associated with abnormal phenotypes, including developmental delay, congenital anomalies, and infertility. In this study, we report four male patients, three of them with de novo rare structural chromosomal rearrangement detected through a combination of Giemsa-Trypsin (GTG) banding, fluorescence in situ hybridization (FISH), and high-resolution microarray techniques (SNP array and array CGH). Each of the four cases turned out to be of a different type: in addition to two exceptional CCRs, an inv dup del 18q and a cluster rearrangement involving the long arm of chromosome 4 were identified. Despite the limitations of the testing methods, we performed a detailed analysis of the relationship between the most detailed genotype data and the associated phenotype. Our study provides further valuable evidence that the use of molecular cytogenetic methods is of paramount importance even in cases with abnormal karyotypes detected by light microscopy, as high-resolution data may reveal unsuspected genomic complexity, which is essential for genetic counseling in these patients. Full article

Considering the contemporary, rapidly evolving society, renewable energy emerges as a key element in advancing both environmental resilience and energy independence. The current study aims to undertake a comparative analysis of the renewable energy adoption between the Old Member States (OMSs) and New Member States (NMSs) of the European Union (EU). This study focuses on regional heterogeneity as well as the role of economic, social, and environmental determinants in shaping effective energy transition policies. This study uses advanced long-term panel estimates such as Dynamic Ordinary Least Squares (DOLS), Fully Modified Least Squares (FMOLS) and Canonical Cointegration Regression (CCR) on a dataset covering the 2010–2023 period. Moreover, this study utilizes quantile regression methods such as Quantile Regression (QREG) and Method of Moments Quantile Regression (MMQR). Finally, this study employs the Dumitrescu–Hurlin test to assess panel causality. The empirical findings reveal notable discrepancies between the two samples when it comes to fossil fuel reliance, income inequality, financial and economic development, the existing level of greenhouse gas emissions, and green finances influencing renewable energy adoption. In the OMS region, a 1% increase in GHG and income inequality reduces the adoption of renewable energy by 0.80–1.14% and 0.61–0.67%, respectively, while a 1% increase in GDP increases the adoption of renewable energy by 0.72–0.92%. In the NMS region, GHG inhibits renewable energy transition by 0.27–0.30%, while fossil fuel energy share, income inequality, green finance, GDP and financial development do not have a significant effect. These results highlight economic development as the key to renewable energy transition in OMSs, while in NMSs, GHG and financial development are key levers. This research seeks to support the developing and restructuring of the existing green framework to enhance its overall effectiveness. Full article

Background: CLEC5A is a C-type lectin expressed by monocytes and neutrophils, playing an important role in innate immunity. Although it has been shown to interact with the spike protein of SARS-CoV-2, its role during vaccination remains poorly understood. Methods: To address this question, we combined in vitro assays to characterize CLEC5A and spike expression and their impact on monocyte differentiation and T-cell activation; in vivo studies to evaluate CLEC5A expression, immune responses, and vaccine efficacy in a murine model; and in silico analyses to identify potential spike epitopes and CLEC5A interaction sites. Results: The Pfizer-BioNTech bivalent mRNA vaccine induced spike expression and CLEC5A upregulation in THP-1 monocytes, promoting M1-like differentiation and CD86⁺ activation. In PBMC co-cultures, CLEC5A⁺ monocytes acted as antigen-presenting cells, releasing inflammatory chemokines and activating both CD4⁺ and CD8⁺ T cells, thereby linking CLEC5A expression to adaptive immunity. In mice, CLEC5A expression was observed on inflammatory monocytes (CCR2⁺CX3CR1^low) within two days of vaccination. In vivo, CLEC5A expression increased during SARS-CoV-2 infection and after immunization, but declined following viral challenge in vaccinated animals. Consistently, robust humoral and cellular responses were detected post-immunization. In silico analysis further suggested differential CLEC5A binding across B- and T-cell epitopes within the spike glycoprotein. Conclusions: These findings suggest that CLEC5A may play a role in bridging innate and adaptive immune responses during SARS-CoV-2 vaccination. Although further studies with different vaccine platforms are necessary to confirm and expand these observations, our results provide preliminary evidence supporting the potential of CLEC5A as an exploratory biomarker of vaccine-induced immunity. Full article