Search Results (35,943)

Studies have shown that the iron concentration in the peritoneal fluid of women is associated with the severity of endometriosis. Therefore, investigation of iron metabolism-related genes (IM-RGs) in endometriosis holds significant implications for both prevention and therapeutic strategies in affected patients. Differentially expressed IM-RGs (DEIM-RGs) were identified by intersecting IM-RGs with differentially expressed genes derived from GSE86534. Mendelian randomization analysis was employed to determine DEIM-RGs causally associated with endometriosis, with subsequent verification through sensitivity analyses and the Steiger test. Biomarkers associated with IM-RGs in endometriosis were validated using expression data from GSE86534 and GSE105764. Functional annotation, regulatory network construction, and immunological profiling were conducted for these biomarkers. Single-cell RNA sequencing (scRNA-seq) (GSE213216) was utilized to identify distinctively expressed cellular subsets between endometriosis and controls. Experimental validation of biomarker expression was performed via reverse transcription–quantitative polymerase chain reaction (RT-qPCR). BMP6 and SLC48A1, biomarkers indicative of cellular BMP response, were influenced by a medicus variant mutation that inactivated PINK1 in complex I, concurrently enriched by both biomarkers. The lncRNA NEAT1 regulated BMP6 through hsa-mir-22-3p and hsa-mir-124-3p, while SLC48A1 was modulated by hsa-mir-423-5p, hsa-mir-19a-3p, and hsa-mir-19b-3p. Immune profiling revealed a negative correlation between BMP6 and monocytes, whereas SLC48A1 displayed a positive correlation with activated natural killer cells. scRNA-seq analysis identified macrophages and stromal stem cells as pivotal cellular components in endometriosis, exhibiting altered self-communication networks. RT-qPCR confirmed elevated expression of BMP6 and SLC48A1 in endometriosis samples relative to controls. Both BMP6 and SLC48A1 were consistently overexpressed in endometriosis, reinforcing their potential as biomarkers. Moreover, macrophages and stromal stem cells were delineated as key contributors. These findings provide novel insights into therapeutic and preventive approaches for patients with endometriosis. Full article

Viral metagenomic next-generation sequencing (vmNGS) has transformed our capacity for the untargeted detection and characterisation of (re)emerging zoonotic viruses, surpassing the limitations of traditional targeted diagnostics. In this review, we critically evaluate the current landscape of vmNGS, highlighting its integration within the One Health paradigm and its application to the surveillance and discovery of (re)emerging viruses at the human–animal–environment interface. We provide a detailed overview of vmNGS workflows including sample selection, nucleic acid extraction, host depletion, virus enrichment, sequencing platforms, and bioinformatic pipelines, all tailored to maximise sensitivity and specificity for diverse sample types. Through selected case studies, including SARS-CoV-2, mpox, Zika virus, and a novel henipavirus, we illustrate the impact of vmNGS in outbreak detection, genomic surveillance, molecular epidemiology, and the development of diagnostics and vaccines. The review further examines the relative strengths and limitations of vmNGS in both passive and active surveillance, addressing barriers such as cost, infrastructure requirements, and the need for interdisciplinary collaboration. By integrating molecular, ecological, and public health perspectives, vmNGS stands as a central tool for early warning, comprehensive monitoring, and informed intervention against (re)emerging viral threats, underscoring its critical role in global pandemic preparedness and zoonotic disease control. Full article

Ocean Alkalinity Enhancement (OAE) is a promising carbon dioxide removal strategy, but its ecological impacts on marine microbial communities under varying nutrient conditions remain poorly understood. We conducted laboratory incubations using a natural North Atlantic microbial assemblage to investigate the response to OAE under both natural and nutrient-enriched regimes. We tracked phytoplankton and bacterioplankton dynamics, biomass, and leucine aminopeptidase (LAP) and alkaline phosphatase (ALP) activity as indicators of organic matter remineralization. OAE consistently reduced phytoplankton abundance in both nutrient regimes, potentially due to CO₂ limitation, resulting in lower production of phytoplankton-derived organic matter. This reduction was reflected in decreased LAP activity and shifts in the relative abundance of phytoplankton-associated bacterial taxa. These findings indicate that OAE can directly affect phytoplankton through carbonate chemistry alterations, with potential microbial responses largely mediated by changes in organic matter availability. While short-term microbial disruptions were modest, the ecological consequences of altered bloom dynamics should be carefully considered in future OAE deployment strategies. Full article

Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. This review aims to consolidate current genomic data across AC subtypes and explore the clinical relevance of recurrent mutations. Methods: A systematic literature review was performed in accordance with general Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. Using search engines such as PubMed and Web of Science, we selected studies based on relevance to AC genomics using search terms such as “appendix cancer”, “appendiceal cancer”, “pseudomyxoma peritonei”, “sequencing”, “mutation”, and “genotype”. Results: AC comprises five major histologic subtypes—appendiceal neuroendocrine neoplasms (ANENs), mucinous appendiceal neoplasms (MANs), goblet cell adenocarcinomas (GCAs), colonic-type adenocarcinomas (CTAs) and signet ring cell adenocarcinomas (SRCs)—each with unique clinical behaviors and mutational profiles. Low-grade tumors, such as ANENs and MANs, frequently harbor KRAS and GNAS mutations, while high-grade subtypes, such as CTAs and SRCs, are enriched for TP53, APC, and SMAD gene alterations. GCA tumors exhibit a distinct mutational spectrum involving chromatin remodeling genes such as ARID1A and KMT2D. Compared to colorectal cancer, AC demonstrates lower frequencies of APC and TP53 mutations and a higher prevalence of GNAS mutations, consistent with a pathological divergence from CRC. Conclusions: The genomic heterogeneity of AC is commensurate with its histological complexity and has important implications for diagnosis, prognosis and treatment. While certain actionable mutations are present in a subset of tumors, large-scale genomic characterization efforts and development of subtype-specific models will be essential for advancing precision medicine in AC. Full article

Accurately predicting the reception area of the Automatic Identification System (AIS) is critical for ship tracking and anomaly detection, as errors in signal interpretation may lead to incorrect vessel localization and behavior analysis. However, traditional propagation models, whether they are deterministic, empirical, or semi-empirical, face limitations when applied to dynamic environments due to their reliance on detailed atmospheric and terrain inputs. Therefore, to address these challenges, we propose a data-driven approach based on graph neural networks (GNNs) to model AIS reception as a function of environmental and geographic variables. Specifically, inspired by attention mechanisms that power transformers in large language models, our framework employs the SAmple and aggreGatE (GraphSAGE) framework convolutions to aggregate neighborhood features, then combines layer outputs through Jumping Knowledge (JK) with Bidirectional Long Short-Term Memory (BiLSTM)-derived attention coefficients and integrates an attentional pooling module at the graph-level readout. Moreover, trained on real-world AIS data enriched with terrain and meteorological features, the model captures both local and long-range reception patterns. As a result, it outperforms classical baselines—including ITU-R P.2001 and XGBoost in F1-score and accuracy. Ultimately, this work illustrates the value of deep learning and AIS sensor networks for the detection of positioning anomalies in ship tracking and highlights the potential of data-driven approaches in modeling sensor reception. Full article

Smart contracts empower many blockchain applications but are exposed to code-level defects. Existing methods do not scale to the evolving code, do not represent complex control and data flows, and lack granular and calibrated evidence. To address the above concerns, we present an across-graph corresponding contract-graph method for vulnerability detection: abstract syntax, control flow, and data flow are fused into a typed, directed contract-graph whose nodes are enriched with pre-code embeddings (GraphCodeBERT or CodeT5+). A Graph Matching Network (GMN) with cross-graph attention compares contract-graphs, aligns homologous sub-graphs associated with vulnerabilities, and supports the interpretation of statements at the level of balance between a broad structural coverage and a discriminative pairwise alignment. The evaluation follows a deployment-oriented protocol with thresholds fixed for validation, multi-seed averaging, and a conservative estimate of sensitivity under low-false-positive budgets. On SmartBugs Wild, the method consistently and markedly exceeds strong rule-based and learning baselines and maintains a higher sensitivity to matching false-positive rates; ablations track the gains to multi-graph fusion, pre-trained encoders, and cross-graph matching, stable through seeds. Full article

The widespread use of neonicotinoid insecticides has led to increasing resistance in non-target organisms, including the egg parasitoid Trichogramma dendrolimi, a crucial biological control agent. Film-residue bioassays on 17 geographic strains revealed striking inter-strain variability in susceptibility to imidacloprid, with mortality at a discriminating dose of 0.1 mg/L ranging from 25.7% to 87%. The most tolerant (FS) and least tolerant (HA) strains were subsequently selected for evaluation of biological parameters and comparative transcriptomics. Tolerant strains (FS) showed adaptive trade-offs: extended longevity (5.47 ± 0.57 d) and emergence (93.6 ± 1.9%), but reduced fecundity (54.6 ± 4.9 eggs) compared to HA. Transcriptome analysis revealed 2115 differentially expressed genes, with GO enrichment highlighting metabolic and detoxification pathways. KEGG analysis the most enriched pathways were “Protein digestion and absorption” and “Neuroactive ligand-receptor interaction”. RT-qPCR confirmed overexpression of CYP4C1, CYP6K1, and GstS1 in FS, indicating their potential roles in metabolic resistance if present. This study presents preliminary evidence of potential fitness trade-offs and molecular mechanisms that could underly imidacloprid resistance in T. dendrolimi, which may lead to important insights for resistance monitoring and more sustainable integrated pest management strategies. Full article

The colon plays a crucial role in energy metabolism and intestinal health of ruminants during various physiological stages. Plateau ruminants have long been subjected to extreme environments characterized by hypoxia, cold, and nutritional scarcity, which makes their dependence on energy metabolism particularly pronounced. However, existing research on the regulatory effects of dietary energy levels on the colonic function of plateau ruminants is still quite limited. This study involved 60 healthy male Pamir yaks with consistent body conditions, which were randomly divided into three groups: a low-energy diet group (YG, Neg 1.53 MJ/kg), a medium-energy diet group (QG, Neg 2.12 MJ/kg), and a high-energy diet group (RG, Neg 2.69 MJ/kg). Each yak was provided with 5 kg of mixed feed daily over a 170-day feeding trial. The results indicated that a high-energy diet enhanced growth performance in yaks (p < 0.05). However, it also induced local colonic inflammation, decreased levels of immune factors (IgA, IgG, and IL-10), and increased the abundance of potentially pathogenic bacteria, such as Klebsiella and Campylobacter (p < 0.05). Conversely, a medium-energy diet fostered the proliferation of beneficial bacteria such as Bradymonadales, Parabacteroides, and Mogibacterium (p < 0.05), and preserved immune homeostasis. Additionally, multi-omics analysis revealed that the QG group was significantly enriched in key metabolic pathways, including pyruvate metabolism and glycine, serine, and threonine metabolism and panto-thenate and CoA biosynthesis pathways, among others (p < 0.05), demonstrating a synergistic regulatory effect among the microbiome, metabolism, and host. In summary, a moderate-energy diet can promote the proliferation of beneficial bacteria in the extreme environment of the plateau. By regulating pathways such as Amino acid, Nucleotide, and Lipid metabolism, it coordinates the expression of key host genes and metabolite levels, effectively balancing immune signals and energy metabolism. This interaction establishes a beneficial microbial-metabolism-host pattern that supports colon health. Full article

Background: Extracellular vesicles, particularly exosomes, play a crucial role in cell–cell communication and as carriers of biomarkers. However, their use in clinical settings is limited due to a lack of standardized isolation and characterization. Ultracentrifugation (UC) is considered a gold standard for exosome isolation but presents several limitations. Size-exclusion chromatography (SEC) has recently gained attention as a superior method, which offers better yield, purity, and protection of exosome physical properties. This study focused on optimizing the SEC method for isolation of exosomes from seminal plasma and comparing yield, quality, and proteome profiles with those obtained by UC. Methods: In this SEC method, seminal plasma (0.5 mL) was loaded onto a SEC column and collected in 13 fractions of 0.4 mL each. The physical and molecular characterization of exosomes was carried out using a ZetaView analyzer and Western blot, respectively. Further, SEC-isolated exosomes were used for proteomic profiling and functional bioinformatic analysis. Results: The second and third fractions had the highest concentration of exosomes with uniform size and strong expression of exosome markers. Also, comparative proteomic analysis identified 3315 proteins in SEC-isolated exosomes and 931 in UC-isolated exosomes, with 709 proteins in common. SEC-isolated exosomes showed greater overlap with Vesiclepedia’s and ExoCarta’s top 100 lists than UC-isolated exosomes (Vesiclepedia: 91 vs. 77 proteins, ExoCarta: 94 vs. 79). Proteins from SEC- and UC-isolated exosomes showed similar enrichment profiles across all three gene ontology categories. Conclusions: Overall, this optimized SEC protocol is a reliable alternative method to isolate seminal exosomes with high purity, supporting its potential applications in clinical and basic research. Full article

Oxidative reactions accelerate quality loss in emulsified meats. This study evaluated a clean-label strategy in goat meat pates by co-fortifying Portulaca oleracea powder 1% and honey 4%. Control and treatment batches were cooked to 72 °C and stored as opened packs at ≤6 °C for 10 days. Oxidative stability of lipid and protein was monitored by peroxide value (PV), TBARS, acid value, and baseline protein carbonyls; total antioxidant capacity was assessed by FRAP and DPPH; color was quantified in CIE Lab; fatty acids were profiled by GC-FID; and protein integrity was examined by SDS-PAGE. The treatment modestly increased α-linolenic acid (ALA) (1.2% vs. 0.8%) in the control and markedly enhanced antioxidant status (FRAP 10.5 ± 0.04 mg GAE/g vs. not detected; DPPH 33.02 ± 0.009% vs. 22.33 ± 0.007%; IC₅₀ 106.10 ± 10.01 vs. 138.25 ± 11.15 µg/mL). Across storage, PV showed a small, non-significant delay on day 10 (13.0 ± 0.9 vs. 14.0 ± 0.9 meq/kg), while secondary and hydrolytic indices were consistently lower (TBARS day 10: 1.91 ± 0.13 vs. 3.29 ± 0.23 mg MDA/kg; acid value day 10: 7.0 ± 0.5 vs. 8.5 ± 0.6 mg KOH/g). Protein carbonyls at baseline were comparable (99.19 vs. 95.73 nmol/mg). L* and b* remained similar before and after light exposure, with a modest, non-significant reduction in color stability and greater a* loss in the treatment. These results show that purslane–honey co-fortification nutritionally enriches pates and attenuates oxidative spoilage during refrigerated storage, with minor color trade-offs that merit process optimization. Full article

The poultry red mite (PRM) feeds on hens’ blood at night, disrupting sleep, harming welfare, and reducing productivity. Effective control may lie in dynamic Integrated Pest Management (IPM), which relies on routine monitoring and adaptation to farm conditions. This study investigated how PRM infestations affect the night-time activity of hens. Three groups of eight hens, housed in enriched cages, were monitored with night-vision cameras over a two-month period, both before and after artificial PRM introduction, while PRM levels were simultaneously recorded. To quantify changes in behaviour, we developed an activity-monitoring algorithm that extracts both group-level and individual night-time activity patterns from video recordings. Group activity between 18:00 and 03:00 was analyzed hourly, and individual activity between 21:00 and 00:00 was classified into four activity categories. Before infestation, group activity declined after 19:00, remained low from 20:00 to 01:00, and peaked just before the end of the dark period. After infestation, activity remained elevated with no anticipatory activity peak towards the end of the dark period. Individual data showed an increase in time spent in the most active activity category from 24% to 67% after infestation. The rise in calculated activity was supported by a nearly 23-fold increase in annotated PRM-related behaviours, specifically head shaking and head scratching. These findings suggest that PRM mostly disrupted sleep from two hours after lights-off to two hours before lights-on and may have acted as a chronic stressor. Automated video-based monitoring could strengthen dynamic IPM in commercial systems. Full article

Grassland ecosystems, a major component of the global carbon (C) and nitrogen (N) cycles, are increasingly impacted by anthropogenic N addition. However, a comprehensive, integrated assessment of all three major greenhouse gas (GHG) responses in grasslands is lacking. Here, we present the first global meta-analysis to evaluate the effects of N addition on all three major GHGs (i.e., nitrous oxide (N₂O), methane (CH₄), and carbon dioxide (CO₂) fluxes) in grasslands. Our results show that N addition significantly and consistently stimulates N₂O emissions, a response primarily modulated by key drivers such as grassland type, management, N addition rate and forms, humidity index (HI), and soil pH, clay, and total nitrogen (TN) content. In contrast, N addition has a minimal and non-significant overall effect on soil CO₂ fluxes. For CH₄, N addition causes a context-dependent reduction in uptake, an effect that is exacerbated by high mean annual precipitation (MAP) and soil bulk density (BD) but alleviated by high soil organic carbon (SOC) content. Notably, both CO₂ and N₂O showed a dose-dependent effect, while soil CO₂ fluxes were unexpectedly suppressed by nitrate nitrogen (NO₃⁻) addition. Our findings indicate that the pronounced and consistent increase in N₂O emissions is the dominant factor in GHG-related impacts in grasslands, implying a net positive climate forcing in grasslands from N enrichment, even if there is insufficient data to calculate net climate forcing directly. Our study highlights the heterogeneous nature of grassland GHG responses and provides critical insights for developing sustainable N management strategies to mitigate climate change. Full article

Diterpenoid diester alkaloids (DDAs) are the primary toxic constituents in aconite herbs, while also being the key pharmacologically active components. Consequently, establishing rapid enrichment and highly sensitive analytical methods for DDAs is of critical importance. Herein, we developed and constructed a gas–liquid microextraction (GLME) device, which enables the rapid and selective enrichment of DDAs from complex matrices. The enriched extract can be directly analyzed by high-resolution Orbitrap mass spectrometry without requiring any further pretreatment. A comparative analysis of six commonly used Aconitum herbs medicines and their processed derivatives was conducted. Notably, GLME enhanced the mass spectrometric signals of DDAs by 3–4 orders of magnitude, facilitating the identification of 27 alkaloids, including 3 potential new compounds (15-Ethyl-13-deoxyanhydroaconitine, 13-Hydroxy-15-ethylanhydroaconitine and 8-eicosapentaenoic-benzoylmesaconine). It was found that among the tested samples, the DDAs response intensity of raw Caowu was the highest, and the DDA signals decreased significantly after processing. This result chemically validates the detoxification efficacy of traditional methods. The proposed GLME-MS strategy has the advantages of being green, economical, easy to operate, and highly selective (>1000-fold), which provides a technical reference for the rapid detection, safety assessment, and quality control of Aconitum herbs. Full article

Chlorophyll-a is a key indicator characterizing the health of marine ecosystems. This study aimed to assess eutrophication risk by investigating the spatio-temporal evolution of chlorophyll-a in the South China Sea (SCS). Based on MODIS-Aqua remote sensing data from 2003 to 2024, five spatial interpolation methods were compared, and Ordinary Kriging was selected as the optimal method (r = 0.96) for reconstructing the chlorophyll-a distribution. The findings indicate that chlorophyll-a is higher in winter and autumn than in summer and spring, with significant enrichment observed near coastal areas. Concentrations decrease with increasing distance from the shore. The Mekong River estuary consistently exhibits high values, while the concentration in the SCS Basin remains persistently low. Furthermore, the spatial extent where chlorophyll concentrations exceed the bloom threshold was evaluated to highlight potential eutrophication risk. These results provide a scientific basis for understanding the response mechanism of the SCS ecosystem to climate change and have important implications for regional marine environmental management and ecological conservation. Full article

Background: Tumor-associated macrophages (TAMs) are essential regulators of the glioblastoma (GBM) microenvironment; their functional heterogeneity and interaction networks are not fully elucidated. We identify RNF135 as a novel TAM-enriched gene associated with immune activation and adverse prognosis in GBM. Methods: To evaluate RNF135’s expression profile, prognostic significance, and functional pathways, extensive transcriptome analyses from TCGA and CGGA cohorts were conducted. The immunological landscape and cellular origin of RNF135 were outlined using single-cell RNA-seq analyses and bulk RNA-seq immune deconvolution (MCP-counter, xCell and ssGSEA). Cell–cell communication networks between tumor cells and RNF135-positive and -negative tumor-associated macrophage subsets were mapped using CellChat. Results: RNF135 predicted a poor overall survival and was markedly upregulated in GBM tissues. Functional enrichment analyses showed that increased cytokine signaling, interferon response, and innate immune activation were characteristics of RNF135-high samples. Immune infiltration profiling showed a strong correlation between the abundance of T cells and macrophages and RNF135 expression. According to the single-cell analyses, RNF135 was primarily expressed in TAMs, specifically in proliferation, phagocytic, and transitional subtypes. RNF135-positive TAMs demonstrated significantly improved intercellular communication with aggressive tumor subtypes in comparison to RNF135-negative TAMs. This was facilitated by upregulated signaling pathways such as MHC-II, CD39, ApoE, and most notably, the CCL signaling axis. The CCL3/CCL3L3–CCR1 ligand–receptor pair was identified as a major mechanistic driver of TAM–TAM crosstalk. High RNF135 expression was also linked to greater sensitivity to Selumetinib, a selective MEK1/2 inhibitor that targets the MAPK/ERK pathway, according to drug sensitivity analysis. Conclusions: RNF135 defines a TAM phenotype in GBM that is both immunologically active and immunosuppressive. This phenotype promotes inflammatory signaling and communication between cells in the tumor microenvironment. Targeting the CCL–CCR1 axis or combining RNF135-guided immunomodulation with certain inhibitors could be a promising therapeutic strategies for GBM. Full article