Search Results (1,441)

Background: Observational studies have linked psychotic disorders to impaired lung function and respiratory diseases, but the potential association between mood swings—a potential predisposing factor for psychotic disorders—and lung health remains poorly understood. Methods: Using summary-level data from large-scale genome-wide association studies, we investigated the shared genetic basis and putative causal links between mood swings and lung function, asthma, and chronic obstructive pulmonary disease (COPD). Results: Evident genetic correlations in our study were observed between mood swings and FEV1 (r_g = −0.09), FVC (r_g = −0.09), PEF (r_g = −0.09), asthma (r_g = 0.33), and COPD (r_g = 0.28). Local genetic correlation analysis identified 10 significant local genomic regions, including chr17p12-p11.2 and chr16q23.1. Furthermore, cross-trait meta-analysis revealed 55 SNPs shared between mood swings and lung function, 2 SNPs with asthma, and 1 SNP with COPD. A transcriptome-wide association study identified 43 shared genes that largely overlapped with those revealed in the cross-trait meta-analysis, implicating tissues in the nervous, respiratory, digestive, and cardiovascular systems. Mendelian randomization analysis provided evidence that mood swings are significantly linked to reduced FEV1 (OR = 0.85, 95% CI = 0.77–0.93), reduced FVC (OR = 0.86, 95% CI = 0.77–0.96), reduced PEF (OR = 0.82, 95% CI = 0.74–0.91), and an elevated risk of asthma (OR = 2.22, 95% CI = 1.60–3.06) and COPD (OR = 2.02, 95% CI = 1.37–2.98). Conclusions: This study highlights a shared genetic basis and putative causal relationship between mood swings and impaired lung function and respiratory diseases, providing genetic evidence that underscores the importance of investigating mood instability in the context of respiratory health. Full article

Colonoscopy remains the gold standard for colorectal cancer (CRC) screening, but its invasiveness, cost, and limited availability in resource-constrained settings pose major barriers. Stool-based methylated DNA biomarkers, such as vimentin, offer sensitive, non-invasive alternatives. Given the high burden of HIV and helminth co-infections in sub-Saharan Africa and their potential contribution to cancer susceptibility, this study investigated whether stool-derived vimentin methylation could detect early oncogenic changes in these high-risk groups. In this retrospective cross-sectional study, archived stool samples from 62 South African adults were stratified into five groups: uninfected controls, HIV-infected only, helminth-infected only, HIV-helminth co-infected, and CRC-confirmed patients. DNA was extracted, bisulfite-converted, and analyzed for vimentin methylation using a high-resolution melt assay. Fecal occult blood testing (FOBT) was also performed. Vimentin methylation differed significantly across groups (p < 0.0001). CRC cases showed 90% methylation, confirming its role as a CRC biomarker. Interestingly, vimentin methylation frequencies were also observed in HIV-only (92.9%, p < 0.0001 vs. controls), helminth-only (93.3%, p < 0.0001), and HIV-helminth co-infected (77.9%, p < 0.0001) individuals without diagnosed cancer, compared to 10% in controls. Methylation levels in infected groups were not significantly different from CRC patients (all p > 0.05), suggesting infection-induced epigenetic changes of comparable magnitude to malignancy. To support these results, DNMT1–RG108 molecular docking (PDB 4WXX, Maestro 2025-3) demonstrated stable binding (GlideScore −6.285 kcal/mol; ΔG_bind −49.61 kcal/mol) via hydrogen bonding with Glu1266 and Asn1578 and π–π stacking with Phe1145, providing a mechanistic explanation for infection-driven vimentin methylation. No significant differences were found between infected groups. FOBT was positive in 83.3% of CRC cases, with only sporadic positives in infected groups. These findings provide novel evidence that chronic HIV and helminth infections are associated with vimentin promoter methylation at levels indistinguishable from CRC. This supports the hypothesis that persistent infection-driven inflammation promotes early epigenetic reprogramming toward oncogenesis. In high-burden African settings, stool-based methylation assays could serve as early diagnostic tools to identify at-risk individuals long before clinical disease manifests, enabling targeted surveillance and prevention. Full article

Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, n = 10), post-test high cardiac remodeling group (AH, n = 10), pre-test low cardiac remodeling group (BL, n = 10), post-test low cardiac remodeling group (AL, n = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise. Full article

This paper presents the theoretical and methodological foundations of Living a Life of Meaning and Purpose-C (LAMP-C), a novel quantitative instrument designed to assess meaning-making capacity among emerging adults to be used as part of a battery of assessments for religiosity. Drawing on Constructive-Developmental Theory (CDT) as articulated by Robert Kegan, Sharon Daloz Parks, and Marcia Baxter Magolda, LAMP-C operationalizes complex developmental constructs such as cognitive, interpersonal, and intrapersonal growth. LAMP-C integrates CDT with the Rasch/Guttman Scenario (RGS) methodology, which systematically structures items to reflect incremental developmental complexity. An instrument for assessing meaning-making contributes to the comprehensive interpretation of assessments of religiosity among emerging adults. By framing meaning-making through four facets—ideation, relational awareness, conflict resolution, and sense of responsibility—this paper provides a comprehensive conceptual foundation for measuring growth in meaning-making. The RGS methodology further enhances construct validity by enabling precise, context-specific, and developmentally sensitive assessments across three contexts. LAMP-C bridges the gap between qualitative depth and quantitative breadth in assessing developmental constructs, offering a tool that supports both large-scale applications and nuanced theoretical alignment. LAMP-C establishes a framework for assessing meaning-making while setting the stage for future empirical research (e.g., longitudinal studies) to evaluate religiosity in emerging adults. Full article

Background/Objectives: T cell bispecific antibodies (TCBs) result in the activation of T cell receptor signaling upon binding to tumor antigens providing signal 1 to T cells. To enhance and sustain their activity, a co-stimulatory signal 2 is required. Here CEACAM5-targeted 4-1BBL antibody fusion proteins for combination with CEA-TCB (cibisatamab, RG7802) are described in an investigation of the relationship between the CEACAM5 epitope and T cell activity. Methods: CEACAM5-targeted bispecific 4-1BBL antibody fusion proteins (CEA-4-1BBLs) were generated based on different CEACAM5 antibodies and characterized in vitro in Jurkat-4-1BB reporter and PBMC cell assays. The impact of shed CEA on in vitro activity and cynomolgus cross-reactivity was studied. In vivo efficacy was assessed in human stem cell humanized NSG mice xenograft models bearing MKN-45 and HPAFII tumors. Results: MFE23-4-1BBL and Sm9b-4-1BBL showed superior functional activity in Jurkat-4-1BB reporter and primary T cell assays when combined with the CD3 antibody V9, whereas T84.66-LCHA-4-1BBL and A5B7-4-1BBL performed better when combined with CEA-TCB. In humanized NSG mice MKN-45 and HPAFII xenograft models, T84.66-LCHA-4-1BBL mediated the best anti-tumor efficacy. Conclusions: For the assessment of the combination of CEA-TCB with CEA-4-1BBL, co-stimulatory antibody fusion protein in vitro assays are not sufficient to fully capture the complex relationships affecting efficacy. Thus, screening with different cell assays and in vivo efficacy studies in combination with CEA-TCB are essential to select the best candidate. Based on the totality of data on the T84.66-LCHA-4-1BBL antibody fusion protein comprising the CEACAM5 antibody, T84.66-LCHA was selected as the optimal combination partner for CEA-TCB. Full article

This paper addresses the challenge of cooperatively escorting a moving underwater target, such as a human-occupied vehicle (HOV), using a multi-AUV formation in complex ocean environments. We propose a comprehensive framework, RG-SAPF scheme, that integrates a rigidity graph (RG)-based reconfigurable formation control strategy with a safe artificial potential field (SAPF) motion planning method. The RG-based controller enables the AUVs to form and dynamically reconfigure a 3D escort formation around the target using only relative position information, ensuring the target remains within the formation’s convex hull. Meanwhile, the SAPF algorithm, enhanced with an adaptive Widrow–Hoff rule, enables real-time and collision-free path planning in obstacle-rich environments. Simulation and experimental results demonstrate that the proposed method effectively maintains formation integrity, supports flexible obstacle avoidance, and provides continuous target escort under dynamic conditions, validating its potential for practical underwater escort applications. Full article

Ice accretion alters the airfoil profile of the unmanned aerial vehicle (UAV), degrading the aerodynamic performance and potentially triggering safety incidents. The computation of droplet impingement characteristics is the primary task for ice accretion analysis and the design of anti-icing/de-icing systems for UAVs. To address the disadvantages of the conventional Eulerian method and the Lagrangian method, a streamline-based Eulerian method is established to obtain the droplet impingement characteristics. It only solves the momentum equation to derive the velocity field, eliminating the computational load of the droplet continuity equation. Droplet streamlines are generated via backward integration in the droplet velocity field, allowing impingement characteristics to be calculated. In this scheme, the droplet collection efficiency is computed without the predetermination of droplet release locations or tracking a large number of droplet trajectories. The proposed method is applied to obtain the droplet collection efficiencies in the cases of an NACA0012 airfoil, a two-dimensional (2D) cylinder, an MS (1)-0317 airfoil, and an RG-15 airfoil. The results show good agreement with the data in the literature; therefore, the feasibility and effectiveness of this streamline-based Eulerian method are confirmed. This work can provide a reference for ice accretion analysis and anti-icing/de-icing system design for UAVs. Full article

Background: Human cell lines underpin modern biomedical research, offering reproducibility, standardisation, and unrestricted access to biological material. Among the 1206 human lines documented in the Human Protein Atlas, in vitro systems overcome the ethical and technical constraints of primary tissues. The liver is an organ of intricate structure, diverse physiological roles, and limited in vitro viability. Liver-derived cell lines are increasingly used to address the growing burden of liver disease and to accelerate pharmaceutical development, yet their capacity to replicate native hepatic functions remains uncertain. The mutational profiles and expression patterns of hepatocyte-characteristic genes provide critical benchmarks for their suitability for pharmacology and toxicology. Methods: Here, we systematically compare ten widely used hepatic cell lines (HepG2, Huh7, Hep3B, LX-2, HepaRG, HLF, HLE, MHCC97H, SK-Hep1, PLC/PRF/5) with primary hepatocytes and liver tissue, focusing on drug-metabolizing enzyme (DME) gene expression. Beyond literature synthesis, we analysed pre-processed RNA-seq expression data. Results: Overall, among the models examined, the HepaRG cell line shows the greatest similarity to liver and primary hepatocytes, most faithfully reproducing the expression patterns of DME genes. HepG2, Hep3B, and Huh7 form a cluster that retains only a subset of hepatic characteristics. Other models display more pronounced deviations from the reference profile and are generally used for specialized applications. Thus, no universal cell line exists that can fully substitute for the liver. Each model has its own limitations and biases in the expression profile of DME genes, which must be carefully considered when selecting an appropriate system for specific research objectives. Full article

This study elucidates the hepatoprotective mechanisms of heat-processed Gynostemma pentaphyllum (Thunb.) Makino saponins (HGyp) against APAP-induced liver injury using serum pharmacochemistry, metabolomics, and network pharmacology. HGyp significantly mitigated liver damage in mice, as confirmed by biochemical and histopathological analyses. UPLC-MS identified 38 bioactive compounds, including 16 prototype saponins and 11 metabolites. Network pharmacology and molecular docking revealed damulin A/B, gypenosides (L/LI/LVI/XLVI), and ginsenosides (Rg3/Rd) as key components targeting GRB2, FGF2, MMP2, STAT3, CASP3, and HSP90A. Western blotting confirmed the HGyp-mediated downregulation of hepatic HSP90A and STAT3. Metabolomics identified four critical pathways, PPAR, ferroptosis, and the inflammatory mediator regulation of TRP channels involved in hepatoprotection. HGyp exerts multi-target effects via anti-inflammatory activity, apoptosis, and metabolism, providing a framework for Chinese medicine and ethnomedicine research. Full article

Large-scale computer simulations were employed to investigate the conformational response of the spike protein components S1 and S2 using a coarse-grained model. Temperature was systematically varied to assess the balance between stabilizing residue–residue interactions and thermal fluctuations. The resulting contact profiles reveal distinct segmental reorganization and self-assembly behaviors between S1 and S2. At lower, thermoresponsive temperatures, pronounced segmental globularization occurs in the N-terminal domain (NTD; M153–K202) and receptor-binding domain (RBD; E406–E471) of S1, whereas S2 exhibits alternating regions of high and low contact density. Increasing temperature reduces this segmental globularization, leaving only minor persistence at elevated temperatures. The temperature dependence of the radius of gyration (R_g) further demonstrates the contrasting thermal behaviors of S1 and S2. For S1, R_g increases continuously and monotonically with temperature, reaching a steady-state value approximately 50% higher than that at low temperature. In contrast, S2 displays a non-monotonic response: R_g initially rises to a maximum nearly sevenfold higher than its low-temperature value, then decreases with further temperature increase. Scaling analysis of the structure factor reveals that the globularity of S1 diminishes significantly upon heating, while S2 becomes modestly more compact yet retains its predominantly fibrous character. Full article

Background/Objectives: To elucidate the differential transcriptional and intercellular signaling features of tumor components across various cancers, we conducted a comparative analysis using single-cell RNA sequencing (scRNA-seq). This technology enables detailed characterization of tumor ecosystems and may explain variations in tumor behavior among distinct cancer types. Methods: We analyzed publicly available scRNA-seq datasets (GEO) from seven cancer types—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), thyroid cancer (TC), gastric cancer (GC), and colorectal cancer (CRC)—to define their unique molecular characteristics and intercellular interactions. Results: PDAC displayed a distinct tumor microenvironment (TME) dominated by myeloid cells (~42%), including abundant CXCR1/CXCR2-expressing tumor-associated neutrophils (TANs) that preferentially interacted with immune rather than cancer cells. The competitive receptor ACKR1 was minimally expressed on endothelial cells, consistent with PDAC hypo-vascularity. In HCC, tumor cells lacked EPCAM and expressed complement and stem cell markers; cancer-associated fibroblasts (CAFs) were scarce, and stellate cells expressed the pericyte marker RGS5. CAFs were abundant in ESCC and BC, with IGF1/2 expression, while in GC, these markers were uniquely found in plasma cells. Since BC and GC subtypes exhibit distinct TME patterns, it is necessary to perform subtype-specific analyses for these cancers. TC showed high expression of tumor-suppressor genes, including HOPX, in tumor cells. Differential interactions and the presence of “dominant signaling cell populations “ with dominant outgoing signals may underlie the heterogeneity in tumor aggressiveness across these cancers. Conclusions: Comparative scRNA-seq analysis of multiple cancers reveals distinct tumor phenotypes and cell–cell communication patterns, offering insights into the molecular architecture of human solid tumors. Full article

SERBP1 (SERPINE1 mRNA-Binding Protein 1), as an RNA-binding protein with multiple biological functions, has become a research hotspot in the field of life sciences in recent years. Its unique molecular structure, such as the presence of RG/RGG repeat sequences and the absence of typical RNA-binding domains, enables it to exert diverse roles in cells. This article systematically reviews the research progress of SERBP1 in various fields including cellular stress response, tumorigenesis and development, reproductive system regulation, nervous system function, and viral infection, elaborates on its mechanism of action in detail (including newly supplemented content on cell cycle regulation, interaction with PARP1, and ribosome biogenesis), and outlines future research directions. It aims to provide a reference for in-depth understanding of the biological functions of SERBP1 and the diagnosis and treatment of related diseases. Full article

NOD-like receptor protein 3 (NLRP3) inflammasome is a key mediator of inflammation and a promising therapeutic target. However, the discovery of novel and effective inhibitors of NLRP3 remains limited. A combined docking-based virtual screening (DBVS) and shape-based screening approach was applied to eight traditional Chinese medicine (TCM) databases to identify potential NLRP3 inhibitors. Structural similarity analysis, ADMET prediction, and molecular dynamics (MD) simulations were performed to evaluate structural novelty, pharmacokinetic properties, and binding stability. A total of 25 potential NLRP3 inhibitors were identified, each exhibiting docking scores higher than those of the reference inhibitor XE3. Structural similarity analysis revealed that the screened compounds exhibited low similarity to previously reported NLRP3 inhibitors, demonstrating their structural novelty. ADMET evaluation indicated that compounds C2, C3, and C4 exhibited favorable physicochemical and pharmacokinetic properties. Molecular dynamics (MD) simulations demonstrated that the complexes of compounds C2, C3, and C4 with NLRP3 remained stable throughout the simulations, exhibiting limited backbone fluctuations and compact conformations, as indicated by Rg values of approximately 6 Å. Solvent-accessible surface area (SASA) and polar surface area (PSA) analyses suggested that compounds C3 and C4 were tightly solvated and maintained favorable membrane permeability. Notably, binding free energy calculations revealed that all three compounds exhibited stronger binding than XE3, with compound C3 showing the most favorable energy (–48.81 ± 3.89 kcal/mol), indicating a highly stable and energetically preferred interaction with NLRP3. This study identified promising TCM-derived compounds as potential NLRP3 inhibitors, offering new directions for anti-inflammatory drug development. Full article

Oropouche virus (OROV), an emerging orthobunyavirus of increasing public health concern in the Americas, currently lacks approved antiviral therapies. In this study, we employed a structure-based in silico approach to identify natural antiviral scaffolds capable of targeting the Gc glycoprotein, a class II fusion protein essential for host membrane fusion and viral entry. A library of 537 plant-derived compounds was screened against the Gc head domain (PDB ID: 6H3X) through molecular docking and redocking, followed by 100-nanosecond molecular dynamics simulations, MM-PBSA free energy calculations, and ADMET profiling. Curcumin and Berberine emerged as standout candidates. Curcumin demonstrated a balanced profile, with stable binding (−38.14 kcal/mol), low backbone RMSD (1.82 Å), and consistent radius of gyration (Rg ~ 18.8 Å), suggesting strong conformational stability and compactness of the protein–ligand complex. Berberine exhibited the most favorable binding energy (−13.10 kcal/mol) and retained dynamic stability (RMSD 1.86 Å; Rg ~ 19.0 Å), though accompanied by predicted cytotoxicity that may require structural refinement. Both compounds induced reduced residue-level fluctuations (RMSF < 2.5 Å) in functionally critical regions of the Gc protein, consistent with a mechanism of action that involves stabilization of the prefusion conformation and interference with the structural transitions required for viral entry. These findings identify curcumin and berberine as promising scaffolds for anti-OROV drug development and offer a rational foundation for future experimental validation targeting viral fusion mechanisms. Full article

Integrated permitting systems are being progressively implemented by governments worldwide owing to their beneficial effects on site-level environmental management. However, different countries have implemented different systems that reflect their own national conditions, resulting in varying efficacy. Based on experience from Korea, here, we propose an e-permit system that implements (i) package management of industries related to or within the value chain of permitted industries, (ii) site-specific best available techniques (BATs), (iii) automatic calculations of BAT-associated emission levels (BAT-AELs), and (iv) code-based management of environmental factors using a ReGreen-BAT (RG-BAT) diagram. The e-permit system improves permitting process efficiency and reduces the review period from 35 days to 2–23 days depending on the industry sector. Additionally, by leveraging big data collected through the Integrated Environmental Permitting System for post-permit management, administrative efficiency could be further improved. Integrating industries related to or within the value chain of the target industries in the Integrated Environmental Management System (IEMS) can reduce pollution, improve resource circulation, and promote energy efficiency and cost savings. When selecting BATs, the balloon effect and internal site-specific factors should be evaluated to realize more tailored and acceptable BAT selection. Automation of BAT-AEL calculations using Python considerably reduces the processing time to 2–3 weeks. The RG-BAT diagram helps visualize BAT effectiveness and allows businesses to easily identify suitable BATs. The insights gained herein indicate that countries implementing IEMS can benefit from sharing implementation experiences and should collaborate on the development of advanced systems. Full article