Search Results (13,303)

This paper investigates biharmonic conformal immersions of surfaces into a conformally flat 3-space. We first establish a characterization of such immersions of totally umbilical surfaces into a generic 3-manifold. It is then proved that any biharmonic conformal immersion of a totally umbilical surface into a nonpositively curved 3-manifold is necessarily a conformal minimal immersion. We further examine the biharmonicity of conformal immersions of totally umbilical planes into a conformally flat 3-space and construct explicit examples of such immersions from a 2-sphere (minus a point) into a conformally flat 3-sphere. Finally, the study is extended to biharmonic conformal immersions of Hopf cylinders associated with a Riemannian submersion. Full article

Xeroderma pigmentosum group B (XPB/ERCC3) and group D (XPD/ERCC2) helicases are integral components of the transcription factor IIH (TFIIH) complex, coordinating DNA unwinding during transcription initiation and nucleotide excision repair (NER). XPB functions as an ATP-driven translocase that generates torsional strain to promote promoter melting and DNA opening at lesion sites, whereas XPD acts as a 5′ to 3′ helicase responsible for lesion verification and extension of the repair bubble. Structural and biochemical studies have clarified how TFIIH subunits regulate these helicases—p52 and p8 modulate XPB’s translocation activity, while p44, p62, and MAT1 control XPD’s helicase function through conformational and compositional transitions within the complex. Beyond their canonical roles, XPB and XPD participate in diverse cellular pathways, including cell-cycle regulation and oxidative stress response, highlighting their involvement in maintaining genome integrity beyond repair and transcription. Mutations in either helicase lead to xeroderma pigmentosum (XP), trichothiodystrophy (TTD), or combined XP/Cockayne syndrome (XP/CS) phenotypes, emphasizing the essential role of TFIIH integrity for human health. Recent biochemical and pharmacological advances have further revealed the therapeutic relevance of these helicases—XPB as a target of small-molecule inhibitors such as triptolide, Minnelide, and spironolactone, and XPD as a potential modulator of cancer sensitivity to DNA-damaging treatments. Collectively, XPB and XPD exemplify the structural and functional versatility of TFIIH helicases across repair, transcription, and genome maintenance. Full article

The escalating global burden of Ulcerative Colitis (UC) underscores the urgent need for novel therapeutic strategies. Although dietary modulation is known to influence UC progression, the specific molecular mediators remain largely undefined. Recently, the G protein coupled receptor 35 (GPR35) has emerged as a promising target for maintaining gut homeostasis and promoting intestinal epithelium repair. Yet, whether the therapeutic benefits of dietary polyphenols are mediated through the direct activation of GPR35 remains unexplored. Here, the NanoLuc Binary Technology (NanoBiT) assay was first used to identify the potential GPR35 agonist from a library of 30 natural polyphenolic compounds. We discovered Ellagic acid (EA), a natural polyphenol abundant in fruits and nuts, as the potent GPR35 agonist owing to its most potent agonistic effect. The dose-dependent effect was further confirmed by both NanoBiT and Bret assay. Then, the binding site of the ligand-receptor complex was predicted via molecular docking, and key interactions were validated by site-directed mutagenesis. The results indicated the key binding site of the complex was Gln93, Arg100, Arg151, Phe163 and Ser262. And the conformation of the complex was verified stable by the molecular dynamics simulation. The bioactivity of EA was then evaluated in vivo. And the in vivo experiment indicated that EA alleviated the symptoms of UC. In addition, complementary in vitro assays, including a wound healing (scratch) assay and an SRB proliferation assay, were employed to investigate its effect on intestinal epithelial repair. The in vitro experiment demonstrated that EA enhanced the migration and proliferation of human colonic epithelial cells, an effect that was specifically abolished by the GPR35 antagonist CID2745687, indicating the key role GPR35 played in the intestinal repair. Collectively, our study demonstrates that the natural polyphenolic compound EA promotes epithelial healing and ameliorates colitis by acting as a GPR35 agonist. Full article

Stochastic Subspace Identification (SSI) theory offers the distinct advantage of extracting modal parameters directly from operational ambient excitations without requiring artificial force, ensuring completely true boundary conditions and providing extensive field measurement data. In this study, we systematically investigate the operational modal characteristics of Electric Multiple Units (EMUs) in the Chinese high-speed railway network under multi-dimensional coupling conditions, including wide speed ranges, axle load perturbations, air spring faults, and coupled operation. The results reveal that while car body modal frequencies remain largely insensitive to operating speed—indicating negligible effects of aerodynamic stiffness—they exhibit distinct sensitivities to mass and boundary variations. Specifically, an increase in axle load induces a significant attenuation (exceeding 5%) in low-order vertical bending frequencies, conforming to the dynamic mass law. Conversely, air spring deflation triggers a sharp increase in boundary stiffness, resulting in a 13.6% surge in torsional modal frequency, which serves as a critical indicator for fault diagnosis. Furthermore, coupled operation is found to primarily enhance system damping. Based on these findings, we establish a “condition-modal” vehicle sensitivity matrix, quantifying dynamic evolution mechanisms under complex boundaries and providing a vital baseline for monitoring the structural health of railway vehicles and conducting intelligent maintenance. Full article

Infection with SARS-CoV-2, the virus responsible for COVID-19, is associated with cytokine storm, an excessive immune response. Interleukin-6, a multifunctional cytokine, is involved in the COVID-19 immune response. Functional polymorphisms in the interleukin-6 gene promoter, namely rs1800796, rs1800797, and rs2069845, may contribute to individual susceptibility to or severity of COVID-19. In this study, 106 healthy SARS-CoV-2-negative individuals (controls) and 106 patients with severe COVID-19 (COVID-19 group), confirmed by qPCR or rapid antigen tests, were genotyped using fluorescent probes for polymorphisms. All participants were from southern Brazil. Groups were matched for sex and body mass index, with a median age of 56–57 years. The COVID-19 group exhibited blood biomarker concentrations consistent with severe disease. No significant differences were detected in genotypic or allelic frequencies between groups, and all polymorphisms conformed to the Hardy–Weinberg equilibrium. The control group minor allelic frequencies for rs1800796 (allele C, 11.3%; 95% CI, 7–16), rs1800797 (allele A, 28.3%; 95% CI, 22–34), and rs2069845 (allele G, 36.8%; 95% CI, 30–50) were similar to those of African, American, and European populations. The polymorphisms investigated were not associated with severe COVID-19 in this cohort. Full article

Traditional methods for geostressfield inversion face issues such as weak physical interpretability and insufficient generalization ability. This study pioneers the application of Physics-Informed Neural Network (PINN) to this problem, developing a data- and physics-driven inversion algorithm. The framework incorporates a constitutive-equation-based regularized loss function as a hard constraint during training to ensure physical consistency. To address boundary load uncertainty, two quantification approaches—Bayesian linear regression and surrogate model optimization—are proposed to establish 95% confidence intervals for boundary coefficients. Verification based on simple three-dimensional models and actual geological models of mines shows that PINN inversion achieves a mean absolute relative error as low as 0.0772%, with an error of 15.67% under sparse sampling conditions—significantly lower than the 31.07% error of the traditional Back propagation neural network. This demonstrates excellent robustness and data efficiency. In the practical engineering application of complex geological bodies, the average error of principal stress inversion is 9.35% with a minimum error of 0.137%. All inversion results fall within the permissible accuracy range of engineering, and the stress distribution conforms to basic laws, with an average error of 0.453 in the constitutive relation. Compared with BP neural network and multiple linear regression methods, it shows obvious accuracy advantages. This method provides a new solution for intelligent ground stress prediction with high accuracy, high efficiency, and strong physical interpretability, and also lays the foundation for early identification of geological disasters. Full article

The islet amyloid polypeptide (IAPP) is a peptide hormone playing key biological roles, including glucose homeostasis and regulation of food intake, conferring high therapeutic potential to treat metabolic disorders. Nonetheless, IAPP is mainly known as the major component of the amyloid fibrils observed in the pancreatic islets of patients afflicted with type 2 diabetes, and the accumulation of these insoluble protein deposits correlates closely with the loss of pancreatic β-cells. The inherent aggregation propensity of this peptide hormone is not only associated with the pathogenesis of type 2 diabetes but also complicates the design of IAPP derivatives for the treatment of metabolic disorders. Accordingly, elucidating the molecular mechanisms by which IAPP self-assembles into amyloid fibrils is critical to identify chemical strategies to arrest aggregation, as well as to design safe and stable IAPP-derived therapeutics. This review aims at presenting the different mechanistic models of IAPP aggregation and how to exploit this information to identify inhibitors of amyloid formation and non-aggregating peptide agonists. After discussing the conformational conversions allowing IAPP to undergo a mainly disordered monomeric conformation into ordered cross-β-sheet quaternary supramolecular structures, we present chemical strategies to prevent amyloid deposition and to develop non-aggregating peptide-based therapeutics. Full article

With the deepening of fifth-generation mobile communication technology (5G) commercialization and the surge in demand for intelligent connectivity of all things, the sixth-generation mobile communication technology (6G) has entered a phase of technological breakthroughs. The innovation in antenna design will determine the upper limits of 6G communication. This paper systematically reviews the research progress on antenna technology for 6G communications, focusing on operating frequency bands, antenna structure design, and materials and packaging technologies. The development of 6G communication technology drives antenna research toward higher-frequency bands, with the current research focus extending from the millimeter wave (mmWave) band to the terahertz (THz) band. Compared to the traditional mmWave band, the THz band shows significant advantages in performance indicators. At the antenna structure level, its development trend is mainly reflected in the following three aspects: size miniaturization, scale expansion and distributed deployment, and expansion of frequency bands and functions. New materials and advanced packaging have become key enabling technologies: materials with low-loss characteristics and tunable surface conductivity have become research focuses. Meanwhile, advanced packaging processes achieve miniaturization and high-performance integration of antenna systems. This review aims to provide a systematic technical reference for the research and engineering development of next-generation 6G antennas. Full article

Steroid hormones exert diverse and tissue-specific biological effects despite sharing a conserved tetracyclic scaffold. Among these, anabolic–androgenic steroids (AAS) present a longstanding paradox: structurally related compounds can elicit markedly different anabolic, androgenic, and cardiovascular outcomes. This narrative review integrates advances in steroid structural chemistry, androgen receptor (AR) biology, and intracellular signaling to elucidate the molecular mechanisms underlying anabolic–androgenic dissociation. We summarize classical genomic and emerging non-genomic modes of steroid action, emphasizing how receptor conformation, ligand-binding domain architecture, co-regulator recruitment, and signaling bias shape downstream biological responses. Particular focus is placed on the structure–activity relationships of endogenous and synthetic androgens, with C17-substitution chemistry highlighted as a central determinant of receptor affinity, metabolic stability, pharmacokinetics, and tissue selectivity. By linking molecular structure to receptor-level mechanisms, we contextualize the physiological and pathophysiological effects of major AAS classes used clinically and non-medically, including testosterone esters, 19-nor derivatives, 17α-alkylated steroids, heterocyclic compounds, and halogenated compounds. While much of the mechanistic evidence derives from preclinical models, the integrated framework presented here provides a coherent basis for interpreting divergent anabolic, androgenic, and cardiovascular effects observed in humans. Collectively, this review bridges fundamental steroid biology with applied physiology and sports medicine, offering mechanistic insight relevant to therapeutic development, anti-doping science, and risk assessment of supraphysiological androgen exposure. Full article

In this study, thermal deformation in non-planar, large-scale additive manufacturing (LSAM) was experimentally and numerically investigated. A Bézier-based non-planar build surface was fabricated by CNC machining, and a single layer of ABS was deposited using a hybrid LSAM system. Toolpaths with raster angles of 0° and 45° were generated for surface-conformal printing. Infrared thermography was employed to monitor the thermal history during deposition. A three-dimensional finite element model was developed to simulate transient heat transfer and thermally induced deformation. Experimental deformation was quantified by 3D scanning and compared with simulation results. The results show that the slope geometry strongly influences deformation direction: negative slopes promote contraction, whereas positive slopes lead to upward deflection. Maintaining the material temperature above the glass transition temperature significantly reduces skew deformation. The finite element method predictions demonstrate strong agreement with experimental measurements, with normalized root mean square errors (NRMSEs) of approximately 11% for thermal deformation and 10% for temperature history. The proposed framework enables prediction and mitigation of thermal warping in non-planar polymer additive manufacturing. Full article

Rhizopus oryzae lipase (ROL) is a key enzyme involved in olive oil spoilage and acts as a virulence factor in fungal infections. Natural lipophilic lipase inhibitors are crucial for mitigating economic losses resulting from lipid degradation in stored or decaying olive fruits. This study evaluated a series of enzymatically synthesized piperate esters with varying alkyl chain lengths (butyryl, C4; octyl, C8; dodecyl, C12) for their inhibitory effects on ROL activity. Octyl piperate (C8) demonstrated the highest potency, with IC₅₀ values of 0.05 mg/mL using methods B and C or 0.25 mg/mL using method A. Molecular docking indicated that C8 achieved the most favorable predicted binding energy (Gscore: –11.134 kcal/mol), primarily through hydrophobic interactions (Val329, Ala212, Phe209) and hydrogen bonds with oxyanion hole residues (Ser268, Thr206, Gln241). Molecular dynamics simulations confirmed that C8 maintained stable binding and stabilized the catalytic residues. In comparison, C4 exhibited weaker interactions, and the longer C12 chain induced conformational instability and steric hindrance. These results establish a parabolic structure–activity relationship, identifying the octyl chain (C8) as optimal for ROL inhibition among the tested derivatives. The rational design of lipophilic, biodegradable lipase inhibitors thus positions octyl piperate as a promising candidate for extending olive storage and shelf life, and as a scaffold for developing natural antifungal agents targeting virulent R. oryzae strains. Full article

Dietary fiber (DF) has a profound influence on human health mainly by modulating the gut microbiota. This review provides an overview of DF derived from cereals, legumes, fruits, vegetables, fungi, and seaweeds, specifically addressing the relationship between microbial utilization and source-specific structural characteristics (such as linking patterns, conformation, solubility, and fermentability). Due to these structural properties, different DFs display selective microbial responses that favor fermentation and the production of short-chain fatty acids (SCFAs). These microbial responses and fermentation-derived metabolites associated with DF intake may contribute to reduced risk of obesity, diabetes, inflammatory bowel disease, and other chronic disorders. This review does not address the trial heterogeneity, dose response, safety, and conflicting evidence, and much of the available evidence is largely observational and heterogeneous. Future studies should focus on dose–response trials of defined DF structures with standardized microbiome and metabolomic endpoints, including validation in human interventions. This review summarizes the DF source and structure, selective changes in the microbiota across various study types, including in vitro, animal models, and human studies, and how these relate to overall health. Full article

Neoplasia of the cornea is overall rare, with corneal squamous-cell carcinoma (c-SCC) being most commonly reported in all species. C-SCC pathogenesis has been related to UV exposure in humans and horses, and to papillomavirus infection in humans. In dogs, brachycephalic conformation and chronic keratitis were associated with c-SCC. Corneal vascular tumors have also been exceptionally reported in humans, and rarely in animals. In dogs, they have been suggested to be UV-related. Except for equine c-SCCs, most studies on corneal neoplasms are case reports. The present study aimed to review the literature on epithelial and vascular corneal tumors in dogs, cats, and horses, adding new cases from our archives. Pubmed and Web of Science were searched (1980–2025) using the following keywords: cornea, neoplasia, carcinoma, hemangioma, hemangiosarcoma, dog, cat, and horse. Additionally, 94 new cases of corneal neoplasia were retrieved: 47 dogs (40 epithelial and seven vascular); 29 cats (14 epithelial and 15 vascular) and 18 horses. Signalment, clinical history, and histopathological characteristics were analyzed and compared with the literature. The combined results supported a strong association between brachycephalic dogs and c-SCC occurrence and highlighted the frequent coexistence in the feline species of symblepharon and corneal perforation, with corneal tumors. Full article

In this study, we investigated the genomic basis of key body measurement and weight traits in Iraqi Awassi sheep using a multi-locus genome-wide association approach. A total of 315 yearling animals were phenotyped for body length, chest depth, heart girth, withers height, and body weight, and genotyped using the Ovine 50K SNP BeadChip. Genome-wide association analyses were performed within the BLUPmrMLM framework to improve the detection of loci with moderate-to-small effects. Significant associations were identified using an LOD-based threshold (LOD ≥ 5), followed by positional annotation of nearby genes and functional enrichment analyses to infer their potential biological relevance. Multiple genomic regions were associated with the evaluated traits. Among the most biologically plausible candidate genes were DST and CFAP299 for body length, ADAMTS8 for chest depth, ZFPM1 and OST4 for heart girth, CPEB2 for body weight, and ITGBL1, RBMS3, and THSD7B for withers height. Functional enrichment analyses indicated the involvement of pathways related to integrin-mediated signaling, focal adhesion and integrin complexes, extracellular matrix organization, and post-transcriptional regulation, suggesting coordinated effects of cell–matrix interactions and gene-expression regulation on body size and conformation. Overall, these findings refine the genomic landscape underlying body weight and morphometric variation in Awassi sheep and provide a focused set of loci for future validation and possible application in marker-assisted and genomic selection programs. Full article

The principal difficulty in studying the physico-mechanical and filtration-capacity properties of coals and host rocks under laboratory conditions using core samples lies in reproducing natural thermodynamic conditions characteristic of in situ depths. To address this issue, specialized equipment and methodologies for transferring measurement results are employed, including the Hoek–Brown failure criterion, the structural weakening coefficient, and the development of thermodynamic models. The reliability and accuracy of such measurements are determined by the degree of conformity between the adopted laboratory conditions and natural in situ conditions, the number of samples representing different lithological varieties, and the adequacy of sampling procedures ensuring representativeness. Particular challenges arise when sampling cleated and fractured coals formed under natural stress–strain conditions and contain methane, which significantly influences their physical properties. These difficulties are especially pronounced in prepared-for-mining high-gas-content coal seams of the Karaganda Basin at depths of approximately 700 m, where obtaining representative samples is technically complicated. Reliable values of the physico-mechanical properties of the coal–rock mass are essential for geomechanical calculations aimed at ensuring safe mining of high-gas-content seams through risk assessment of geodynamic phenomena, particularly in zones of geological disturbances, floor heave, and roof collapse. In this context, the use of a comprehensive suite of geophysical logging data from exploration boreholes makes it possible to obtain continuous, high-precision information on physico-mechanical and filtration-capacity properties. These methods are particularly important for characterizing the coal–rock mass in operating mines, since the natural state of host rocks and prepared coal seams is altered due to stress relief caused by mine workings, preliminary degasification measures, and hydraulic fracturing. The problem addressed is the need for reliable assessment of rock and coal seam parameters under natural thermodynamic stress–strain conditions, taking into account lithological composition, structural heterogeneity, fracture development, stratigraphic differentiation, and gas saturation. The aim of this study is to ensure efficient and safe coal extraction based on geomechanical calculations utilizing physico-mechanical and filtration-capacity properties of host rocks and gas-bearing coal seams, whether prepared for mining or not yet extracted. The research methods are based on an integrated complex of geophysical logging of exploration wells, specialized software tools, and statistical processing techniques to identify patterns in physico-mechanical and filtration-capacity properties of host rocks and coal seams under natural stress–strain conditions, as well as to determine the nature of changes in these properties within coal seams and roof and floor rocks in prepared mining areas. The physico-mechanical and filtration-capacity properties of host rocks and coals from the Lenin and Kazakhstanskaya mines were determined. Regularities governing the application of these parameters to coals of different formations and depths were established; fracture orientations and characteristics were evaluated; and relationships between changes in coal seam parameters and gas content were identified. A comprehensive methodological framework for studying the physical and capacity properties of the coal–rock mass under natural thermodynamic conditions has been developed. Its primary application is the investigation of coal seams prepared for mining to support geomechanical calculations for efficient and safe coal extraction, the implementation of degasification measures for high-gas-content seams, and the assessment of gas-dynamic risks based on the character of variations in physical parameters. Full article