Search Results (66,412)

Polystyrene nanoplastics (PS-NPs; nominal diameter, 100 nm; unmodified and negatively charged) and imidacloprid (IMI) are common freshwater contaminants, but little is known about their combined toxicity in benthic fish. In this study, loaches (Misgurnus anguillicaudatus) were exposed for 21 days to clean water, 100 μg/L PS-NPs, 78 μg/L IMI, or 78 μg/L IMI combined with 25, 50, or 100 μg/L PS-NPs. Each treatment contained 90 fish distributed among three replicate tanks. Survival, hepatic oxidative-stress indices, inflammatory gene expression, histopathology, and intestinal transcriptomic and metabolomic profiles were evaluated. Survival decreased across the co-exposure groups, with a significant overall difference among treatments (log-rank test, p = 0.0027). Hepatic CAT, SOD, and GSH levels decreased, whereas MDA increased, with the strongest changes observed in the higher PS-NP co-exposure groups. Pro-inflammatory genes, including IL-1β, IL-6, IL-8, and TNF-α, were upregulated, whereas IL-4 and IL-10 were downregulated. Histopathological injury of the gill, intestine, and liver was most pronounced in the NIH group. Transcriptomic analysis identified changes in pathways related to digestion, cell-cycle regulation, cholesterol metabolism, and lipid metabolism, while metabolomic analysis revealed alterations in glycerophospholipid, sphingolipid, fatty-acid, and carbohydrate metabolism. HMGCS1, CEL, CYP8B1, APOB, and APOC1 showed treatment-associated expression changes, with APOB displaying a non-linear response across the co-exposure groups. Overall, PS-NP co-exposure was associated with stronger IMI-related adverse responses under the tested conditions and substantial disruption of intestinal lipid homeostasis. Full article

This work presents the system-level design, fabrication, and experimental validation of a 1-bit reconfigurable reflectarray with a $12\times 12$ aperture operating at 15 GHz in the Ku-band. Each unit cell consists of a circular microstrip patch with four symmetrically arranged PIN diodes that are driven collectively to realize two reflection states with an approximately ${180}^{\circ }$ phase difference near the operating frequency. The fourfold-symmetric unit cell exhibits similar reflection characteristics for x- and y-polarized incidence. The complete prototype combines four reusable $6\times 6$ subarrays, a modular bias network, and an MCU-based controller that independently addresses all 144 unit cells. Measurements demonstrate beam steering from $-{50}^{\circ }$ to $+{50}^{\circ }$, a maximum measured gain of 17.9 dBi, an aperture efficiency of 17.8%, a cross-polarized level below $-25$ dB, and a 7.9% 1-dB gain bandwidth. The demonstrated combination of wide-angle beam steering, similar unit-cell characteristics for x- and y-polarized incidence, low cross-polarization, and reusable subarray construction provides a practical and scalable hardware approach for Ku-band wireless links, satellite communications, and radar systems. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disability-adjusted life years (DALYs) and all-cause mortality worldwide, imposing an increasing global health burden. Atherosclerosis (AS) is a complex multifactorial disease, and the concept of organ crosstalk has provided a new perspective for understanding its pathogenesis. Although circulating chemerin levels are closely associated with the development and adverse prognosis of ASCVD, the functional heterogeneity and regulatory characteristics of chemerin derived from different tissues have not been systematically investigated. This review elucidates the tissue-specific roles of chemerin in AS from both endocrine and paracrine perspectives, with a focus on chemerin derived from the liver, white adipose tissue, perivascular adipose tissue, and epicardial adipose tissue. Endocrine chemerin primarily contributes to systemic metabolic dysfunction and endothelial injury, whereas locally produced chemerin regulates vascular smooth muscle cell remodeling and vascular inflammation through paracrine signaling. Collectively, endocrine and paracrine chemerin constitute a dual regulatory network that links metabolic abnormalities with vascular remodeling during AS progression. Full article

The mechanical cation channel Piezo1 has been confirmed as a key membrane mechanical protein that can convert physical forces into biological signals, serving as a molecular hub linking hemodynamic stimulation with thrombotic diseases. Studying mechanical sensitive channels in the cardiovascular system is helpful for understanding the working mechanism of these channels and providing new therapeutic targets for thrombotic diseases. This article systematically summarizes the expression and functional roles of the Piezo1 channel in cell types involved in thrombosis, including platelets, endothelial cells, red blood cells, immune cells, etc. This article also discusses the mechanical gating structural basis of Piezo1 and its activation mechanism and downstream signaling pathways in the thrombosis-related mechanical microenvironment. Based on the existing evidence, Piezo1 has significant pathological significance in the occurrence and development of thrombotic diseases, and targeting Piezo1 may provide new strategies for anti-thrombotic treatment. Future research needs to further clarify the differential regulatory mechanisms of the Piezo1 channel in different hemodynamic environments and evaluate its safety and efficacy as a drug target. Full article

In this paper, the solar irradiance is investigated in a part of central Serbia, where a low-cost IoT sensor network was deployed at three locations: a mountain slope, an open field near a village, and an obstructed position in the city center. All three locations are in the same NASA POWER grid cell. After multi-stage quality control, 26,145 valid daytime records were compared to the satellite reference. The satellite assigns identical values to all three positions but the measured mean daytime irradiances are 267.7, 351.5 and 19.6 W/m², respectively. The rural station is in the best agreement with the reference (R² = 0.567); the mountain station suffers from a persistent shading bias (MBE = −138.9 W/m²); the signal at the urban station is attenuated by surrounding buildings and vegetation by a factor of ~12. Also, 25 regression models (gradient boosting, recurrent, convolutional, fully connected and graph-based) were trained on the 25-year monthly NASA POWER record for the same cell. XGBoost obtained R² = 0.998, the hybrid TCN-GNN R² = 0.968 and a plain ReLU network R² = 0.912, and a seasonal model with calendar features was used to reconstruct the satellite reference for two months of 2026 not yet available in the archive. The deployed hardware, network and energy behavior are documented quantitatively: per-site link delivery ratios of 96.8%, 83.5% and 58.2%, the photovoltaic harvesting record of the nodes, and the absence of any energy-aware transmission scheduling. Two of the trained models were compiled for the ESP32 nodes and measured on the deployment hardware: a depth-limited gradient-boosted corrector runs in 46.3 µs using 11.1 kB of flash, and an INT8 fully connected network in 138.1 µs using 3.0 kB, while the graph hybrid cannot be converted for microcontroller execution at all. This defines an edge–cloud partition in which local inference performs bias correction and fault detection while the cloud tier retains the heavy models and periodic retraining. To the best of the authors’ knowledge, this is the first multi-site ground-based IoT irradiance record for central Serbia with such different terrain types. Full article

Background: Cellular heterogeneity limits causal inference in complex diseases. We applied an established cell-type-stratified Mendelian randomization (csMR) framework, originally developed by Hao et al. (2024), to investigate whether lipid phenotypes affect kidney disease through distinct brain cell populations, extended by a proteome-wide mediation component. Methods: Using Bayesian colocalization (posterior probability of hypothesis 4 [PPH4], ≥0.8) and multidimensional instrumental variable selection, we evaluated cell-type-stratified MR-supported associations of five lipid traits across ten brain cell or tissue strata with kidney disease risk. Instrumental variables were derived from published genome-wide association studies and human brain single-cell expression quantitative trait locus (eQTL) maps. An exploratory proteomic mediation analysis using the Difference Method was performed with UKB-PPP as the discovery resource and deCODE as the external validation resource, with mediation signals interpreted as hypothesis-generating. For the primary csMR analysis, multiple testing was corrected separately within each lipid trait using a Bonferroni threshold of 3.33 × 10⁻⁴, corresponding to 150 cell/tissue-by-outcome tests per lipid trait. Results: In csMR analyses, cholesterol-related lipids showed cell-type-stratified associations with kidney disease, most prominently in oligodendrocyte-related analyses (max β on the log-odds scale = 1.025). LDL-related associations with broad chronic glomerular disease were most evident in excitatory neuron-related analyses. Dual-cohort proteomic analysis prioritized plasma proteins, including SNAP29 and ICAM4, as candidate protein-associated signals for exploratory mediation analysis. These findings represent genetic colocalization and Mendelian randomization-supported associations, not experimentally established mechanisms, and should be interpreted as hypothesis-generating. Conclusions: This study provides a cell-type-resolved genetic and proteomic association map linking lipid traits, brain cell strata, and kidney disease outcomes, offering hypotheses for future experimental validation. Full article

High-dimensional monitoring and subspace analysis require contamination-resistant dependence summaries with subquadratic state complexity. Coordinatewise clipping limits individual entries but allows total row contribution to grow with dimension. Dual-Bound Fast Outlier-Robust Correlation Estimation combines fixed median-based calibration, coordinate clipping, parallel and residual contraction, and Frequent Directions sketching to estimate a normalized transformed second moment. Conditional on calibration, an exact-arithmetic companion has a simultaneous row envelope and an error decomposition for sampling, whole-row replacement, and sketch approximation. The implemented dense output is the Gram matrix of a column-normalized sketch factor, which is positive semidefinite in exact arithmetic and shares its factor with the subspace route. Active and peak calibration states are linear in dimension for fixed rank and calibration size before dense-output materialization. Minimax development over 112 configurations selected the reported parameter tuple. In matched-window synthetic experiments, Dual-Bound reduced mean projection error by 0.0858 under casewise and 0.0150 under coordinatewise Cauchy replacement relative to a tuned median-absolute-deviation version of Sketch-based Fast Outlier-Robust Correlation Estimation; clean and bounded structural differences were $-0.0015$ and $-0.0020$. Results depended on configuration and mechanism. External projection and donor-balanced reconstruction errors remained between 0.97 and 1.00, so biological recovery and population validation were not demonstrated. The analysis provides no unconditional calibration or convergence guarantee, no useful guarantee in terms of the cell-fault fraction, and no end-to-end implementation or unconditional floating-point guarantee. These results establish a focused design for conditional transformed-scatter sketching in high-dimensional streams. Full article

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is one of the leading causes of cancer-related deaths globally. Despite current developments, reliable biomarkers for effective diagnosis, prognosis, and patient stratification are still lacking. Methods: We analyzed publicly available TCGA-LUAD and GEO datasets using integrative bioinformatics approaches, including differential gene expression, weighted gene co-expression network analysis (WGCNA), survival modeling, mutation profiling, immune cell infiltration scores, machine learning, and bulk-RNA and single-cell RNA sequencing. Results: A total of 5581 deregulated genes were identified, with the turquoise module (298 genes) showing strong correlation with LUAD (Corr = −0.79, p < 2.2 × 10⁻³⁰⁸). The integration of two analyses yielded 281 overlapping genes, out of which nine candidates (ANO2, CHIAP2, CPED1, DNASE1L3, GSTM5, HTR3C, PRKCE, SLC14A1, and WNT3A) were selected via LASSO Cox regression to build a prognostic risk model. High-risk patients have significantly worse survival (log-rank p = 0.0027). CPED1 exhibited the highest mutation frequency, with 41% of TCGA-LUAD samples harboring mutations. Among all CPED1 mutation events, missense mutations were the most common (47%). GSEA and KEGG analysis revealed significant enrichment of pathways such as nucleocytoplasmic transport, oxidative phosphorylation, protein processing in the endoplasmic reticulum, ribosome, and ribosome biogenesis in high-risk patients. Immune infiltration analysis indicated differences in immune cell infiltration scores between high- and low-immune-score groups, with M1 macrophages showing strong statistical correlation with aDC, monocytes, and CD4⁺ naïve T cells. Machine learning confirmed that the combined Enet+PLS model predicted CPED1 as a core predictor, and CPED1 was successfully validated in independent GEO datasets (GSE43458 and GSE31210), showing strong diagnostic accuracy (AUCs up to 0.98). Finally, single-cell RNA sequencing revealed that CPED1 was mostly expressed in fibroblasts and myeloid cells, with CPED1 significantly downregulated in LUAD compared with normal samples. Conclusions: This study integrates multi-omics and machine learning to highlight CPED1 as a promising candidate biomarker, with potential diagnostic and prognostic relevance in LUAD. The nine-gene risk signature stratified patients by survival outcomes in the TCGA cohort. Genomic and immune analyses revealed features associated with the high-immune-score group. As the study is entirely computational and the prognostic model lacks external survival validation, these findings should be regarded as preliminary and hypothesis-generating, requiring future independent validation and functional studies to confirm the biological significance and clinical utility of CPED1 and related genes. Full article

Background/Objectives: Alginate hydrogels are widely used in tissue engineering; however, their reported properties vary significantly due to differences in formulations and processing conditions, which limits direct comparison across studies. This study aims to systematically evaluate the relative and combined effects of alginate viscosity grade, polymer concentration, and CaCl₂ crosslinking concentration on hydrogel structural, mechanical, and biological behaviour. Methods: Hydrogels were prepared using three commercially available alginates of low, medium, and high viscosity. Polymer concentration (0.5–2% w/v) and CaCl₂ concentration (2.5–10% w/v) were systematically varied under controlled fabrication conditions. Morphology was analysed using scanning electron microscopy, swelling and water uptake were quantified, mechanical properties were assessed via dynamic mechanical analysis, and cell viability was evaluated using Chinese hamster ovary (CHO) cells encapsulation over 20 days. Statistical analysis was performed using two-way ANOVA. Results: Hydrogel properties were governed by non-linear interactions between formulation parameters. CaCl₂ concentration was identified as the dominant factor influencing structural and biological outcomes, with increasing crosslinking concentration reducing pore size, swelling, and water uptake, and decreasing cell viability by up to ~60%. In contrast, polymer concentration and alginate viscosity grade primarily controlled mechanical behaviour, with increased polymer content and viscosity resulting in higher storage and Young’s moduli. Significant interaction effects confirmed that hydrogel properties are not independently tunable but depend on the combined influence of all parameters. Conclusions: Crosslinking concentration dominates structural and biological responses in alginate hydrogels, while polymer parameters modulate mechanical properties within this constraint. These findings establish a formulation-dependent trade-off between mechanical stiffness and cytocompatibility, providing a comparative framework for rational selection of alginate systems based on application-specific requirements. Full article

Background/Objectives: Neonatal sepsis remains a major cause of morbidity and mortality worldwide, underscoring the critical need for early and accurate diagnostic biomarkers. This study aimed to evaluate the predictive value of the red cell distribution width-to-albumin ratio (RAR) for the diagnosis of neonatal sepsis and to compare its diagnostic performance with the C-reactive protein-to-albumin ratio (CAR) and other hematological parameters. Methods: This retrospective cohort study was conducted in the Neonatology Department of Karadeniz Technical University Faculty of Medicine between January 2015 and June 2025. A total of 874 neonates with a gestational age > 36 weeks were included: 411 with blood culture-confirmed sepsis (108 Gram-negative, 303 Gram-positive) and 463 healthy controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cut-off values determined by the Youden index. Results: RAR demonstrated modest diagnostic accuracy for neonatal sepsis, with an area under the curve (AUC) of 0.647 (95% CI: 0.61–0.69), a cut-off value of 5.108, sensitivity of 50.7%, and specificity of 76.7%. RAR was significantly elevated in the Gram-negative group compared with Gram-positive cases and controls (p < 0.001). However, the clinical significance of this subgroup difference requires further investigation. In multivariable logistic regression analysis, RAR remained independently associated with culture-confirmed neonatal sepsis after adjustment for gestational age, birth weight, sex, and mode of delivery (aOR = 2.190, 95% CI: 1.838–2.608, p < 0.001). Among all evaluated markers, CAR achieved the highest diagnostic performance (AUC: 0.981, sensitivity: 88.5%, specificity: 98.7%, PPV: 98.4%, NPV: 90.7%, LR+: 68.47), followed by C-reactive protein (AUC: 0.978), while neutrophil-to-lymphocyte ratio showed the lowest discriminatory ability (AUC: 0.592). Conclusions: RAR showed limited standalone discriminatory performance for culture-confirmed neonatal sepsis, although its association with sepsis remained significant after adjustment for relevant demographic and perinatal factors. CAR demonstrated significantly greater discriminatory performance than RAR. Further studies are needed to determine whether RAR provides incremental value when incorporated into multivariable diagnostic models. Full article

miR-155 is an oncogenic microRNA implicated in breast cancer, but its downstream post-transcriptional targets remain incompletely defined. This study tested membrane-associated RING-CH 7 (MARCH7) as a direct miR-155 target and examined associated molecular and cellular phenotypes in MCF-7 and MDA-MB-231 breast cancer cells. Basal miR-155 expression was assessed in MCF-10A, MCF-7, and MDA-MB-231 cells. MCF-7 cells were analyzed by MTT, RT-qPCR, Western blotting, bioinformatic prediction, dual-luciferase reporter assays, and MARCH7 knockdown; MDA-MB-231 cells were additionally evaluated by MTT, RT-qPCR, wound-healing, and Transwell invasion assays. miR-155 was more abundant in the breast cancer cell lines than in MCF-10A cells. In MCF-7 cells, miR-155 overexpression increased MTT-derived metabolic viability, reduced MARCH7 and PTEN expression, increased Cyclin D1, reduced cleaved caspase-3, and was associated with increased PI3K and AKT phosphorylation. In MDA-MB-231 cells, RT-qPCR confirmed successful miR-155 modulation, whereas MTT changes were modest; these small changes may reflect either model/endpoint differences or limited sensitivity of the MTT assay under the tested conditions. Dual-luciferase assays confirmed direct targeting of the MARCH7 3′-UTR by miR-155, while miR-155 inhibition markedly reduced MDA-MB-231 migration and invasion. These findings establish MARCH7 as a direct miR-155 target in the models examined. The PTEN/PI3K/AKT changes are associated downstream findings and are not yet proven to be mediated specifically by MARCH7. Full article

This study evaluated the effects of dietary SYNSEA Premium postbiotics on growth, immunity, disease resistance, intestinal microbiota, and host metabolism in Asian seabass (Lates calcarifer). Fish were fed a control diet or diets supplemented with heat-killed Lactiplantibacillus plantarum LP28, L. plantarum LP1008, and Bacillus subtilis at 10⁸ (LSP) or 10⁹ (HSP) cells kg⁻¹ diet for 56 days. Postbiotic supplementation did not significantly affect growth performance, feed efficiency, production, condition factor, or dorsal muscle composition, but significantly improved survival. Fish receiving postbiotics also exhibited higher survival following Vibrio alginolyticus and iridovirus challenges. These protective effects were accompanied by enhanced superoxide dismutase, phagocytic, and lysozyme activities and modulation of immune-related genes, including tgf-β1, tnf, ifn-γ1, c3, and mx. Exploratory microbiome and metabolome analyses, which were restricted to the control and LSP groups, identified differences in the relative abundance of specific intestinal microbial taxa and associations between microbial composition and host metabolic profiles. The LSP group showed lower relative abundances of potential pathogens such as Salmonella enterica, Lactococcus garvieae, and Staphylococcus warneri, although the overall microbial community structure did not differ significantly between groups. Metabolomic analysis of the LSP group further showed changes in D-glucose, pentose phosphate pathway intermediates, reduced glutathione, CoA, and 2-methylacetoacetyl-CoA relative to the control. Collectively, SYNSEA Premium improved survival, immune responses, and resistance to bacterial and viral infections without significantly affecting growth performance, while exploratory omics analysis of the LSP treatment identified associated microbial and metabolic changes. Full article

Dengue virus (DENV) serotypes 1–4 cause dengue, a major re-emerging disease in tropical and subtropical regions. This study evaluated the antigenicity of a recombinant DENV-2 premembrane protein (rprM-DENV-2) and its ability to detect anti-DENV human IgA antibodies. The rprM-DENV-2 protein was expressed in Escherichia coli, purified, and assessed for immunogenicity and antigenicity. The recombinant protein induced IgG antibodies in rats, which detected DENV infection in Vero cells. Importantly, in paired saliva and serum samples from patients diagnosed with dengue, IgA antibodies were detected by ELISA using the rprM-DENV-2 antigen, but not in samples from the negative control group (subjects residing in a non-endemic area), with a significant difference (p < 0.0001). These findings demonstrate that rprM-DENV-2 retains antigenic properties similar to the native viral protein; this may be useful for in vitro studies of DENV infection and IgA detection in non-invasive clinical samples. Full article

In recent years, seaweeds have attracted increasing scientific and commercial interest thanks to their protein, lipid and mineral content, and the presence of bioactive compounds that can have a positive impact on health. In light of this, seaweed is an innovative plant food source. This study characterizes commercial edible seaweeds (dulse, wakame, kombu, arame, nori, spirulina), evaluating their mineral composition, with particular attention to toxic or potentially toxic elements, and their fatty acid profile. The results revealed significant differences between species, which are probably related to taxonomic and environmental factors. Brown algae exhibited the highest levels of macroelements, particularly K and Na, which is consistent with their alginate-rich cell walls. Other species exhibited significant concentrations of Fe and Zn, while Pb and Hg remained below regulatory limits. However, nearly all samples exceeded the recommended limits of 0.5 mg/kg for Cd and 3 mg/kg for total As, as defined by the Centre d’Étude et de Valorisation des Algues (CEVA). Additionally, kombu samples had an extremely high iodine content, exceeding the upper CEVA-recommended limit of 2000 mg/kg. These values, therefore, require targeted risk assessments and consumer guidance. The fatty acid profile also appeared to vary by taxa. Red algae, especially nori, were rich in EPA, while brown species showed heterogeneous distributions of SFA, MUFA, and PUFA. Spirulina displayed a distinctive SFA- and n-6 PUFA-rich profile. Overall, the results confirm the need for careful management of iodine, Cd and As levels to ensure that these seaweeds can be used safely as food supplements and to promote their use in innovative food products. Full article

Doxorubicin (Dox)-induced cardiotoxicity (DIC) is a major clinical challenge in cancer therapy. Camel milk exosomes (CMEs) have been applied in anti-tumor treatments as they have a variety of effects, including on inflammation, oxidative stress, metastasis, and apoptosis. However, their role in DIC treatment remains incompletely understood. This research was designed to evaluate the protection provided by CMEs against DIC. The DIC mice were treated with Dox intraperitoneally and divided into a model group and groups treated with different doses of CMEs. Dox-induced H9c2 cell injury was also established and divided into a model group and groups treated with different concentrations of CMEs. The evaluation parameters in vitro included H9c2 cell viability, reactive oxygen species (ROS), mitochondria, and apoptotic cells. The apoptosis and autophagy markers, as well as the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were assessed via Western blotting both in vivo and in vitro. In addition, transcriptome sequencing of cardiac tissue was also applied to investigate the related mechanisms. Our results indicate that CMEs significantly attenuated the cell viability reduction, apoptosis, and ROS production in H9c2 cells caused by Dox. CMEs also regulated autophagy, inhibited apoptosis, and inhibited the NF-κB and MAPK pathways. In conclusion, our findings demonstrate that CMEs exert a cardiac protective effect against DIC by inhibiting apoptosis and regulating autophagy via NF-κB and MAPK signaling pathways. Full article