Search Results (28,522)

Since March 2021, a series of volcanic eruptions on Iceland’s Reykjanes Peninsula has repeatedly triggered wildfires in moss-dominated heathlands—an unprecedented phenomenon in this environment. These fires have consumed extensive organic material, posing emerging health risks and long-term ecological impacts. Using high-resolution multispectral satellite data from the Copernicus program, we present the first quantitative assessment of the spatial and temporal dynamics of volcanic wildfire activity. Our analysis reveals a cumulative burned area extending 11.4 km² beyond the lava flows, primarily across low-relief terrain. Time series of the Normalized Difference Vegetation Index (NDVI) capture both localized fire scars and diffuse, landscape-scale burn patterns, followed by slow and spatially heterogeneous recovery. Complementary ground surveys conducted in August 2024 document diverse post-fire successional pathways, with vegetation regrowth and species composition strongly governed by microtopography and substrate texture. Together, these results demonstrate that volcanic wildfires represent a novel and consequential secondary disturbance in Icelandic volcanic systems, highlighting the complex and protracted recovery dynamics of moss heath ecosystems following fire-induced perturbation. Full article

Background: Inherited retinal dystrophies (IRDs) include a clinically and genetically diverse array of conditions resulting in progressive visual impairment. The PROM1 gene is crucial for the development and maintenance of photoreceptors. Variants in PROM1 are linked to a wide phenotypic spectra of IRDs; however, the correlation between genotype and phenotype is not fully elucidated. Comprehending these relationships is essential for enhanced diagnostic precision, patient guidance, and formulation of focused treatments. Objective: This study aims to examine the genotype–phenotype associations in patients with PROM1-associated IRDs. Clinical variability and inheritance patterns linked to different pathogenic variants are examined, aiming to clarify their different behaviors. Methods: We performed a retrospective investigation of patients identified as affected by PROM1-related IRDs. Thorough ophthalmologic assessments, including retinography, fundus autofluorescence, optical coherence tomography (OCT), and electrodiagnostic testing (EDT), were conducted. Genetic testing was performed via targeted gene panels or whole-exome sequencing. Variants were categorized based on ACMG criteria, and inheritance patterns were determined by familial segregation analysis. Clinical characteristics were analyzed among genotypic groups to ascertain potential phenotype–genotype relationships. Results: All patients had pathogenic or likely pathogenic PROM1 mutations. Both autosomal dominant and autosomal recessive inheritance patterns were identified. Dominant pathogenic variants were predominantly linked to late-onset cone-rod dystrophy or macular dystrophy, whereas biallelic variants frequently resulted in early-onset severe rod–cone dystrophy characterized by fast vision deterioration. A group of patients with the same genotypes displayed significant phenotypic variability, indicating the potential impact of modifier genes or environmental influences. Truncating mutations in the N-terminal region were significantly associated with earlier illness onset and greater functional impairment. Conclusions: PROM1-related IRDs demonstrated significant clinical and genetic heterogeneity, with the route of inheritance and type of variant affecting disease severity and progression. Our findings underscore the significance of thorough genotypic and phenotypic characterization in afflicted individuals. A deeper comprehension of PROM1-related IRD disease pathways can enhance prognosis, direct clinical care, and facilitate the advancement of genotype-based therapy strategies. Full article

Background: Ulcerative colitis (UC), a chronic and relapsing form of inflammatory bowel disease (IBD), arises from a multifactorial interplay of genetic predisposition, immune dysregulation, and environmental triggers. Despite advances in understanding UC pathogenesis, the identification of reliable biomarkers and key regulatory genes remains essential for unraveling disease mechanisms. Such insights are crucial for improving diagnostic precision and developing personalized therapeutic strategies. Methods: In this study, gene expression profiles from publicly available microarray and RNA-sequencing datasets were systematically analyzed using advanced bioinformatics tools. Differentially expressed genes (DEGs) were identified through statistical comparisons, and functional enrichment analyses were performed to explore their biological relevance. A total of 141 overlapping DEGs were extracted from three GEO datasets, and 20 key DEGs were further prioritized via protein–protein interaction (PPI) network construction. Hub genes, relevant signaling pathways, associated transcription factors (TFs), and microRNAs (miRNAs) linked to disease progression were identified. Potential therapeutic compounds were also predicted through computational drug–gene interaction analysis. Results: The analysis revealed a panel of novel biomarkers-TLR2, IFNG, CD163, CXCL9, CCL4, PRF1, TLR8, ARG1, LILRB2, FPR2, and PPARG-that function as key hub genes implicated in ulcerative colitis (UC) pathogenesis. These genes were associated with critical biological processes including signal transduction, inflammatory and immune responses, proteolysis, lipid transport, and cholesterol/triglyceride homeostasis. Furthermore, transcription factors (FOXC1, GABPA, GATA2, SUPT5H) and microRNAs (hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-24-3p, hsa-miR-23a-5p, hsa-miR-26a-5p) revealed key regulatory networks influencing post-transcriptional gene regulation. Molecular docking analysis predicted Apremilast and Golotimod as promising therapeutic candidates for UC intervention. Conclusions: In conclusion, this study enhances our understanding of ulcerative colitis pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies. Full article

Maternal health care during labor requires the continuous and reliable monitoring of analgesic procedures, yet conventional systems are often subjective, indirect, and operator-dependent. Infrared thermography (IRT) offers a promising non-invasive approach for labor epidural analgesia (LEA) monitoring, but its practical implementation is hindered by clinical and hardware limitations. This work presents a novel artificial intelligence-driven mobile platform to overcome these hurdles. The proposed solution integrates a lightweight deep learning model for semantic segmentation, a B-spline-based free-form deformation (FFD) approach for non-rigid dermatome registration, and efficient on-device inference. Our analysis identified a U-Net with a MobileNetV3 backbone as the optimal architecture, achieving a high Dice score of 0.97 and a 4.5% intersection over union (IoU) gain over heavier backbones while being 73% more parameter-efficient. The entire AI pipeline is deployed on a commercial smartphone via TensorFlow Lite, achieving an on-device inference time of approximately two seconds per image. Deployed within a user-friendly interface, our approach provides straightforward feedback to support decision making in labor management. By integrating thermal imaging with deep learning and mobile deployment, the proposed system provides a practical solution to enhance maternal care. By offering a quantitative, automated tool, this work demonstrates a viable pathway to augment or replace subjective clinical assessments with objective, data-driven monitoring, bridging the gap between advanced AI research and point-of-care practice in obstetric anesthesia. Full article

Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications. Full article

This study aimed to elucidate the vasorelaxant mechanism of action for apigenin 7-glucoside (A7G) by integrating computational and ex vivo pharmacological approaches. Molecular docking simulations were conducted to predict the binding affinities and interactions of A7G with key vascular proteins, specifically human endothelial nitric oxide synthase (eNOS-PDB ID: 1M9M), and human intermediate (IKCa-PDB ID: 9ED1) and small-conductance (SKCa-PDB ID: 6CNN) Ca2+-activated K+ channels. The vasodilatory properties of A7G were subsequently evaluated in isolated mesenteric vascular beds (MVBs) from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). The in silico analysis indicated that A7G possesses favorable binding affinities for the 1M9M, 9ED1, and 6CNN protein targets. Pharmacological assessments demonstrated that A7G induced a dose- and endothelium-dependent reduction in perfusion pressure in MVBs from WKY and SHR rats. The vasodilatory response to A7G was completely abrogated by perfusion with a high-potassium solution or a non-selective K+ channelblocker. Furthermore, co-administration of apamin and TRAM-34, selective inhibitors of SKCa and IKCa, respectively, also abolished the vasorelaxant effects of A7G. Collectively, these findings suggest that the vascular effects of A7G in both WKY and SHR rats involve an endothelium-dependent mechanism, likely initiated by the activation of the NO/cGMP pathway, which culminates in the opening of IKCa and SKCa channels. Full article

Przewalski’s gazelle (Procapra przewalskii) is an endangered ungulate endemic to the Qinghai–Tibet Plateau, with a small population size and exposure to multiple ecological pressures. Its gut microbiota may play a crucial role in host environmental adaptation. To investigate the functional divergence of gut microbial communities, we performed high-throughput metagenomic sequencing on 105 wild fecal samples collected from 10 geographic regions around Qinghai Lake. The results revealed significant regional differentiation in key functional modules related to metabolism, antibiotic resistance mechanisms, and virulence-associated pathways. All populations showed enrichment in core metabolic pathways such as carbohydrate and amino acid metabolism, with carbohydrate-active enzymes dominated by glycoside hydrolases (GHs) and glycosyltransferases (GTs), exhibiting overall functional conservation. Although populations shared many antibiotic- and virulence-related reference genetic markers, the marker composition associated with distinct resistance mechanisms and pathogenic processes exhibited clear population-specific patterns, suggesting differential microbial responses to local environmental pressures. Correlation network analysis further identified core taxa (e.g., Arthrobacter and Oscillospiraceae/Bacteroidales lineages) as key genera linking community structure with core metabolic, resistance-related, and virulence-associated marker functions. Overall, the gut microbiota of Przewalski’s gazelle exhibits a complex spatially structured functional differentiation, reflecting host–microbiome co-adaptation under region-specific ecological pressures. These findings provide critical methodological and theoretical support for microecological health assessment and regionally informed conservation management of this endangered species. Full article

The objective of this study is to analyze spatial entropy flows that reveal the directional dynamics of climate change—patterns that remain obscured in traditional statistical analyses. This approach enables the identification of pathways for “climate information transport”, highlights associations with atmospheric circulation types, and allows for the localization of both sources and “informational voids”—regions where entropy is dissipated. The analytical framework is grounded in a quantitative assessment of long-term climate variability across Europe over the period 1901–2010, utilizing Shannon entropy as a measure of atmospheric system uncertainty and variability. The underlying assumption is that the variability of temperature and precipitation reflects the inherently dynamic character of climate as a nonlinear system prone to fluctuations. The study focuses on calculating entropy estimated within a 70-year moving window for each calendar month, using bivariate distributions of temperature and precipitation modeled with copula functions. Marginal distributions were selected based on the Akaike Information Criterion (AIC). To improve the accuracy of the estimation, a block bootstrap resampling technique was applied, along with numerical integration to compute the Shannon entropy values at each of the 4165 grid points with a spatial resolution of 0.5° × 0.5°. The results indicate that entropy and its derivative are complementary indicators of atmospheric system instability—entropy proving effective in long-term diagnostics, while its derivative provides insight into the short-term forecasting of abrupt changes. A lag analysis and Spearman rank correlation between entropy values and their potential supported the investigation of how circulation variability influences the occurrence of extreme precipitation events. Particularly noteworthy is the temporal derivative of entropy, which revealed strong nonlinear relationships between local dynamic conditions and climatic extremes. A spatial analysis of the information entropy field was also conducted, revealing distinct structures with varying degrees of climatic complexity on a continental scale. This field appears to be clearly structured, reflecting not only the directional patterns of change but also the potential sources of meteorological fluctuations. A field-theory-based spatial classification allows for the identification of transitional regions—areas with heightened susceptibility to shifts in local dynamics—as well as entropy source and sink regions. The study is embedded within the Fokker–Planck formalism, wherein the change in the stochastic distribution characterizes the rate of entropy production. In this context, regions of positive divergence are interpreted as active generators of variability, while sink regions function as stabilizing zones that dampen fluctuations. Full article

This study integrates network toxicology with molecular docking technology to systematically elucidate the key molecular mechanisms and signaling pathways by which bisphenol A (BPA) induces obesity. By cross-referencing multiple databases—including the Comparative Toxicogenomics Database (CTD), SwissTarget prediction platform, and PharmMapper—potential BPA target genes were identified, yielding a total of 1326 candidate targets. Obesity-related genes were collected from GeneCards and OMIM databases, yielding 4570 disease-associated targets. Among these, 653 overlapping genes were identified as potential mediators linking BPA exposure to obesity. Protein interaction networks were constructed using STRING and Cytoscape, and the MCC algorithm identified five core hub genes: STAT3, MYC, TP53, IL6, and mTOR. Validation using random datasets demonstrated significant upregulation of these genes in the obesity group (p < 0.05), highlighting their potential central role in BPA-induced obesity effects. Functional enrichment analysis via GO and KEGG pathways indicated that BPA may promote obesity by interfering with endocrine signaling, activating lipid metabolism, and stimulating atherosclerosis pathways. Molecular docking analysis using CB-Dock2 confirmed strong binding affinity between BPA and core targets, providing structural evidence for their potential interactions. This study elucidates the potential biological mechanism by which BPA exacerbates obesity through endocrine disruption and metabolic reprogramming, employing a multidimensional approach encompassing cross-target analysis, pathway enrichment, and molecular interactions. It provides an innovative systems toxicology framework and empirical basis for assessing metabolic health risks induced by environmental pollutants. Full article

Estrogen is a key regulator of skeletal muscle growth and metabolism in birds, yet its specific roles in female chickens remain poorly defined. To address this gap, we established an estrogen-deficient model by surgically removing the ovaries of Wuding hens, a Chinese indigenous slow-growing breed. Growth traits, carcass yield, and meat quality were evaluated across different ages, complemented by histological examination, serum biochemical analysis, and multi-omics approaches (transcriptomics, proteomics, and lipidomics). Ovariectomized hens maintained somatic growth for a longer period and reached greater body weight and carcass yield at 330 days compared with intact controls. Thigh muscle tenderness was also enhanced in the absence of estrogen, despite no long-term differences in muscle fiber morphology. Lipidomic analysis revealed a transient increase in intramuscular triglyceride content at mid-growth (240 days), pointing to altered lipid storage and distribution. Integrated omics profiling further demonstrated significant changes in the mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) signaling pathways, accompanied by differential expression of key metabolic and structural genes, including mitogen-activated protein kinase 8 (MAPK8), fatty acid binding protein 4 (FABP4), ankyrin 1 (ANK1), and coenzyme Q6 monooxygenase (COQ6). These molecular adjustments suggest that estrogen withdrawal triggers broad reprogramming of muscle signaling and lipid metabolism. Overall, this study highlights the multifaceted role of estrogen in coordinating growth, muscle quality, and lipid homeostasis in hens and provides a functional model for studying estrogen deficiency in poultry with implications for meat quality improvement. Full article

Soil salinization threatens global food security, necessitating the development of saline–alkaline-tolerant crops. This study investigated the molecular mechanisms of alkali stress tolerance in maize. Screening 369 inbred lines identified two alkali-resistant and two alkali-sensitive varieties. Systematic analysis revealed that resistant varieties rapidly lowered rhizosphere pH and maintained root architecture, whereas sensitive varieties suffered reduced lateral roots and severe biomass loss. Metabolomic profiling showed that all varieties secreted malonic acid via the pyrimidine pathway to modulate rhizosphere pH, with resistant varieties exhibiting stronger accumulation. Transcriptome and RT-qPCR analysis identified two key genes: Zm00001eb396990 (asparagine synthetase), upregulated in resistant varieties and linked to organic acid synthesis, and Zm00001eb370000 (cytokinin dehydrogenase), downregulated in resistant varieties, potentially aiding root maintenance. Multi-omics correlation confirmed the association between Zm00001eb396990 expression and malonic acid content. This study demonstrates that maize roots can alleviate alkali stress through the secretion of malonic acid and the regulation of related genes, providing potential genetic targets and a theoretical basis for cultivating alkali-tolerant maize. Full article

Methacrylyl-CoA is a key metabolic intermediate in the valine catabolic pathway. Its accumulation has been found to be cytotoxic and associated with pathological conditions. Nevertheless, detailed biological effects of methacrylyl-CoA and methacrylate in human physiology and pathology are poorly understood. We propose that the electrophilicity of the alkene bond in the methacrylyl group can react with the cysteine residues in proteins resulting in an unexplored protein post-translational modification (PTM), cysteine S-2-carboxypropylation (C2cp). To test and validate this mechanistic hypothesis, we experimentally detected and profiled S-2-carboxypropylated proteins from the complex cellular proteome with the design and application of a bioorthogonal chemical probe, N-propargyl methacrylamide. We tested the probe in different mammalian cell models and demonstrated its versatility and sensitivity to protein cysteine S-2-carboxypropylation. We established quantitative chemical proteomics for global and site-specific profiling of protein S-2-carboxypropylation, which successfully identified 403 S-2-carboxypropylated proteins and 120 cysteine modification sites from HEK293T cells. Through bioinformatic analysis, we found that C2cp-modified proteins were involved in a variety of critical cellular functions including translation, RNA splicing, and protein folding. Our chemoproteomic studies demonstrating the proteome-wide distribution of cysteine S-2-carboxypropylation provide a new biochemical mechanism for the functional investigation of methacrylyl-CoA and understanding valine-related metabolic disorders. Full article

Heavy metal (HM) contamination in agricultural soils poses a significant threat to soil health and plant productivity. This study investigates the impact of cadmium (Cd) and zinc (Zn) stress on tomato plants (Solanum lycopersicum) and explores the mitigation potential of microbial biostimulants (MBs), including arbuscular mycorrhizal fungi (AMF) and Pseudomonas fluorescens So_08 (PGPR), over a 52-day period using multi-omics approaches. Root exudate profiling revealed distinct metabolic changes under HM stress, which compromised soil–plant interactions. Cd stress reduced the secretion of phenylpropanoids (sum LogFC: −45.18), lipids (sum LogFC: −27.67), and isoprenoids (sum LogFC: −11−67), key metabolites in antioxidative defense, while also suppressing rhizosphere fungal populations. Conversely, Zn stress enhanced lipid exudation (such as sphingolipids and sterols, as sum LogFC of 8.72 and 9.99, respectively) to maintain membrane integrity and reshaped rhizobacterial communities. The MBs application mitigated HM-induced stress by enhancing specialized metabolite syntheses, including cinnamic acids, terpenoids, and flavonoids, which promoted crop resilience. MBs also reshaped microbial diversity, fostering beneficial species like Portibacter spp., Alkalitalea saponilacus under Cd stress, and stimulating rhizobacteria like Aggregatilinea spp. under Zn stress. Specifically, under Cd stress, bacterial diversity remained relatively stable, suggesting their resilience to Cd. However, fungal communities exhibited greater sensitivity, with a decline in diversity in Cd-treated soils and partial recovery when MBs were applied. Conversely, Zn stress caused decline in bacterial α-diversity, while fungal diversity was maintained, indicating that Zn acts as an ecological filter that suppresses sensitive bacterial taxa and favors Zn-tolerant fungal species. Multi-omics data integration combined with network analysis highlighted key features associated with improved nutrient availability and reduced HM toxicity under MB treatments, including metabolites and microbial taxa linked to sulfur cycling, nitrogen metabolism, and iron reduction pathways. These findings demonstrate that MBs can modulate plant metabolic responses and restore rhizosphere microbial communities under Cd and Zn stress, with PGPR showing broader metabolomic recovery effects and AMF influencing specific metabolite pathways. This study provides new insights into plant–microbe interactions in HM-contaminated environments, supporting the potential application of biostimulants for sustainable soil remediation and plant health improvement. Full article

Formaldehyde (FA) is commonly used for hatchery disinfection, where it reduces microbial growth, ensures successful egg hatch and enhances healthy production, but its specific effects on embryonic development remain unclear. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and may mediate FA-induced transcriptional responses. Here, we investigated the impact of FA treatment on miRNA profiles in chicken embryo liver. Small RNA-seq libraries were constructed and sequenced using the Illumina NextSeq platform. Reads were trimmed and quantified using miRDeep2 version 2.0.0.3. Differential expression analysis was performed with DESeq2 (p-adjusted < 0.05 and |log2FC| > 1). Target genes of differentially expressed miRNAs (DEMs) were predicted with miRDB, and GO/KEGG/Reactome enrichment was conducted. Out of 662 total mature miRNAs detected, differential expression analysis identified 30 DEMs (11 up-regulated, 19 down-regulated). The highest fold increase was determined for gga-miR-3533 (log2FC = 4.45), and the most significant decrease was determined for gga-miR-133b (log2FC = −3.38). Pathway analysis revealed miRNAs affecting signaling pathways along with modules related to post-translational protein modification, immune system, and oxidative stress pathways. Our study demonstrates that FA treatment can affect critical biological processes by altering miRNA-mediated regulation in the developing embryonic liver and point to the need for functional validation of miRNA-target interactions to help determine mechanisms for FA benefits. Long term, these data may help serve as reference to identify new treatments with optimized response profiles. Full article

Acute kidney injury (AKI) is a leading cause of distant organ dysfunction among critically ill patients. Mitochondrial dysfunction is considered a key factor driving the damage after renal ischemia–reperfusion (IR) injury. Damaged mitochondria release mitochondrial damage-associated molecular patterns (mtDAMPs) into the cytosol, which initiate a systemic inflammatory response. To better understand the underlying mechanism, mice were challenged with 30 min of bilateral renal ischemia followed by 24 h of reperfusion. The cytokine profiling in mouse lung tissues revealed that TREM-1 was significantly increased. Western Blot (WB) analysis demonstrated that the cGAS and STING pathway was increased in AKI mice. Transmission electron microscopy (TEM) images indicated that the mtDAMPs were released from damaged kidney mitochondria. Injection of mtDAMPs into mice induced an inflammatory response in the lungs similar to that induced by AKI. Mouse macrophages and lung epithelial cells were utilized to verify if inhibition of the TREM-1 and cGAS-STING pathways reduces mtDAMP-induced lung injury. Electric Cell-substrate Impedance Sensing (ECIS) results demonstrated that inhibiting the TREM-1 and cGAS-STING pathways significantly increased cell proliferation and migration while reducing mtDAMP-induced cytotoxicity. In conclusion, our findings suggest that targeting TREM-1 and cGAS-STING has the potential to attenuate acute lung injury in IR-AKI. Full article