Search Results (1,765)

Background/Objectives: The preschool period is critical for neurodevelopment, yet evidence investigating fortified formula’s effect and potential microbiota–gut–brain axis mechanisms in this age group is limited. To evaluate fortified formula milk’s effect on neurodevelopment and explore potential microbiota–gut–brain axis mechanisms in preschool children. Methods: In this 9-month cluster-randomized, double-blind, controlled trial, 120 healthy children aged 3–6 years from four kindergarten classes were stratified by grade and randomly allocated (1:1) to receive either multi-nutrient fortified formula (intervention, n = 60) or standard control milk (n = 60). Neurocognitive function was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Safety was evaluated through anthropometry and blood biochemistry. Gut microbiota (16S rRNA sequencing) and fecal metabolomes (untargeted LC-MS) were analyzed at baseline and 9 months. Results: The intention-to-treat (ITT) analysis showed no significant difference in Full Scale Intelligence Quotient (adjusted mean difference: 1.05 points; 95% CI: −1.42, 3.52; p = 0.400). However, the intervention group significantly improved the Processing Speed Index (adjusted mean difference: 5.91 points; 95% CI: 1.88, 9.93; p = 0.004), increased gut microbial alpha diversity (Shannon index) and Bifidobacterium abundance. Metabolomic analysis revealed elevated fecal 2-hydroxybutyric acid (2-HB), a marker of propanoate metabolism. Increases in both Bifidobacterium and 2-HB levels showed a positive association with PSI improvement (both p < 0.05). All children maintained normal growth and safety parameters. Conclusions: Fortified formula milk improved processing speed in preschoolers, a benefit associated with gut ecosystem modulation characterized by Bifidobacterium enrichment and upregulated microbial propanoate metabolism. These results offer preliminary evidence for the role of the microbiota–gut–brain axis in nutritional cognitive programming during early childhood. (Clinical Trial Registry: ChiCTR2400084211). Full article

Background and Clinical Significance: Neurosarcoidosis (NS) is a rare manifestation of systemic sarcoidosis involving the central nervous system, with highly variable neurological and endocrine presentations. Among these, anterior pituitary dysfunction is particularly uncommon and diagnostically challenging. Case Presentation: We report the case of a 37-year-old woman with a 4-year history of secondary amenorrhoea and an initially suspected pituitary microadenoma, who was ultimately diagnosed with probable NS presenting with multiaxial anterior pituitary insufficiency. Early magnetic resonance imaging (MRI) revealed a small pituitary lesion and isolated pituitary stalk thickening, without other central nervous system abnormalities. Subsequent imaging demonstrated contrast-enhancing lesions involving the meninges and cranial nerves, along with progression of pituitary stalk involvement and loss of the posterior pituitary bright spot. Further evaluation confirmed systemic sarcoidosis. High-dose corticosteroid therapy led to partial clinical and radiological improvement; however, relapse necessitated methotrexate, and persistent pituitary hormone deficiencies required long-term hormonal replacement. Conclusions: This case highlights the diagnostic complexity of NS presenting with isolated endocrine dysfunction and subtle imaging findings. It underscores the need to consider systemic sarcoidosis in patients with unexplained hypopituitarism. Full article

Background: Wearable sensors have gained increasing popularity as an objective method for remotely monitoring infant movement in naturalistic settings. Over the first year of life, infants generate a wide range of motions, from goal-directed to spontaneous movement. These include linear movements, such as kicks, and orientation changes, such as postural transitions. Many sensor processing pipelines emphasize capturing linear movements through movement-generated acceleration while focusing less on information about orientation embedded in the gravitational part of the data. Here, we introduce a complementary gravity-referenced approach that extracts the gravitational component of accelerometer signals to estimate limb orientation, extending the reliable quantification of rich and detailed aspects of infant movement. Infant orientation has demonstrated clinical relevance, including associations with later neuromotor outcomes, and it can be used to chart infant motor development, motivating the development of objective methods to quantify orientation from sensor data. Methods: Wearable sensors (Opal APDM) were used to longitudinally evaluate infant motor activity recorded in sessions conducted at 3, 6, 9, and 12 months of age. We extracted data from a 5 min segment that has simultaneous video recordings. From these datasets, applying the gravity-referenced method, we computed pitch, roll, and yaw, angles that collectively describe limb orientation. We then quantified orientation variability using axis-specific circular standard deviations (SDs) for pitch, roll, and yaw and a multi-axis composite measure based on generalized variance. Results: Axis-specific circular SDs for pitch, roll, and yaw, as well as the composite generalized variance, increased significantly from 3 to 12 months (p ≤ 0.01 for each metric). Composite variability was strongly associated with Mullen gross motor outcomes at 9 and 12 months of age (r = 0.55, p < 0.001). Conclusions: Overall, gravity-referenced pitch, roll, and yaw provide rich orientation features that increased as infants develop more postural transitions. Furthermore, the orientation features correlated with standardized measures of infant motor function. These orientation metrics can complement traditional linear kinematic measures and improve our ability to granularly track infant motor development in the first year of life. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)–vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome–IGF-1–VEGF–retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP. Full article

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. The Shen-Kang Recipe (SKR) is a traditional Chinese medicine formula used clinically to slow DKD progression, but its bioactive constituents and molecular targets remain unclear. Solute carrier family 15 member 2 (SLC15A2/PEPT2), a high-affinity peptide transporter expressed in renal proximal tubules, has been implicated in kidney pathophysiology, yet its potential role in mediating the therapeutic effects of the SKR has not been explored. Here, we evaluated the effects of the SKR in db/db mice and found that SKR treatment significantly improved renal function, attenuated glomerulosclerosis, and reduced interstitial collagen deposition. Wide-target metabolomics and quantitative proteomics revealed that the SKR broadly reversed DKD-associated metabolic and proteomic disturbances, particularly in pathways related to energy and amino acid metabolism. Proteomic analysis identified SLC15A2 as a key proximal tubule protein downregulated in DKD and selectively restored by the SKR. UPLC-Q-TOF/MS-based serum pharmacochemistry and network pharmacology highlighted quercetin as a principal bioactive component of the SKR. Molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) confirmed direct, high-affinity binding between quercetin and SLC15A2 (KD = 7.5 µM). In TGF-β1-stimulated HK-2 cells, quercetin suppressed epithelial-mesenchymal transition (EMT), as evidenced by restored E-cadherin and reduced N-cadherin, vimentin, and α-SMA expression; this effect was abrogated by siRNA-mediated SLC15A2 knockdown, demonstrating the functional necessity of this axis. Collectively, these findings identify a quercetin-SLC15A2 axis through which the SKR inhibits EMT and alleviates renal fibrosis in DKD, providing a mechanistic basis for its clinical application and nominating SLC15A2 as a potential therapeutic target. Full article

At present, most of the research methods for vibration fatigue of welded structures mainly focus on uniaxial stress, ignoring the influence of shear stress. To this end, by combining the ASME structural stress method with the random and vibration analysis theory outlined in the IEC 61373 standard, a new method for evaluating the fatigue life of multi-axis random vibration problems in the frequency domain has been proposed. This method extends the structural stress method to multi-axis scenarios to accurately extract the local multi-axis structural stress state at the weld toe. Its advantage lies in the fact that it not only accounts for the influence of load frequency distribution and structural modal vibrations on fatigue life, but also incorporates the effect of local multiaxial stress conditions in the weld on fatigue life. Additionally, it includes corrections for non-proportional multiaxial stress conditions, resulting in fatigue assessment results that more closely reflect actual conditions. It was validated by comparing the local multiaxial stress, phase difference between shear and normal stress, and equivalent structural stress power spectrum of 0° and 30° fillet welded specimens with test results. Subsequently, it was applied to a multiaxial random vibration fatigue assessment of a vehicle-mounted electrical cabinet with experimental verification. The results indicate that fatigue life estimates based on a multi-axis stress state are lower than those obtained using a uniaxial method. Compared to traditional uniaxial methods, the multi-axis fatigue life estimates show a significant reduction ranging from 4.20% to 88.35%, effectively accounting for damage caused by shear stress. The fatigue assessment results are more closely aligned with experimental data, thereby validating the effectiveness of the proposed new method. The frequency-domain multiaxial random vibration fatigue assessment method proposed in this article provides a new technology for the design and evaluation of welded structures of vehicle-mounted equipment in rail vehicles. This method reduces costs during the design phase of rail vehicles, offering positive economic implications. Full article

Micro- and nanoplastics (MPs/NPs) have emerged as pervasive environmental contaminants with increasing implications for human health, particularly within the digestive system. This review critically examines the role of MPs/NPs as disruptors of gastrointestinal and liver homeostasis through the lens of the plastic–gut–liver axis. We synthesize current evidence on primary exposure routes—including ingestion, inhalation, dermal contact, and transplacental transfer—and highlight their intestinal uptake, systemic dissemination, and tissue accumulation. Mechanistically, MPs/NPs compromise intestinal barrier integrity, promote oxidative stress, and induce microbiota dysbiosis, facilitating the translocation of microbial-derived signals to the liver via the portal circulation. This process triggers inflammatory signaling cascades, metabolic reprogramming, and immune dysregulation, contributing to hepatic steatosis, insulin resistance, and potential carcinogenic processes. Emerging evidence also implicates pancreatic dysfunction and β-cell stress within a broader gut–liver axis context. We further discuss the systemic propagation of MPs/NPs-induced dysbiosis along multi-organ axes, including gut–lung and gut–brain interactions. Despite robust preclinical data, human evidence remains limited due to methodological heterogeneity and the lack of standardized biomarkers. This review underscores critical knowledge gaps and emphasizes the need for integrative, translational approaches to clarify long-term health risks and inform regulatory strategies within the environmental exposome framework. Full article

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by excessive keratinocyte proliferation, oxidative stress, and dysregulated cytokine signaling. Although topical corticosteroids remain the first-line therapy, their long-term use is often limited by adverse effects, highlighting the need for safer non-steroidal therapeutic alternatives. This study investigated the therapeutic efficacy and underlying mechanisms of a topical astaxanthin (AST) formulation in an imiquimod (IMQ)-induced mouse model of psoriasiform dermatitis. Following IMQ induction, mice were randomly assigned to vehicle, clobetasol, or AST treatment groups (0.5–1.5%) for 14 days. Disease progression was evaluated through biochemical analysis of oxidative stress biomarkers, including NADPH oxidase (NOX), malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD), as well as ELISA-based quantification of inflammatory cytokines (TNF-α, IL-6, IL-17, and IL-23). Histopathological changes were assessed using hematoxylin and eosin staining, while molecular alterations were examined by RT-qPCR analysis of psoriasis-associated keratin genes (Krt16, Krt17, and Krt6a) and evaluation of JAK–STAT signaling activity. AST treatment significantly suppressed the IL-23/IL-17 inflammatory axis, reduced NOX activity and lipid peroxidation, restored endogenous antioxidant defenses, and inhibited JAK–STAT signaling. These biochemical and molecular effects were accompanied by marked downregulation of keratin gene expression and substantial histological improvement, including normalization of epidermal thickness, reduced parakeratosis, and decreased inflammatory infiltration. Notably, high-dose AST demonstrated therapeutic efficacy comparable to, and in some parameters exceeding, that of clobetasol. Collectively, these findings indicate that topical astaxanthin exerts coordinated antioxidant, anti-inflammatory, and anti-proliferative effects, supporting its potential as a promising multi-target non-steroidal therapeutic candidate for psoriasis management. Full article

As an efficient solid–liquid separation device, the hydrocyclone is widely applied in various industrial fields such as coal preparation and oil impurity removal, and its classification performance directly determines the efficiency of industrial separation operations., As the core separation zone of the hydrocyclone, the cone segment, its structure and the number of cone angles directly affect the flow field distribution characteristics and particle classification performance of the hydrocyclone. To reveal the regulation mechanism of the combined cone angles on the classification performance of hydrocyclones, numerical analysis and experimental verification methods were adopted to investigate the internal flow field and classification performance of hydrocyclones under different cone angle combinations. The evolution laws of velocity field, pressure field, turbulence characteristics, and particle classification effect under different configurations were systematically explored. The results show that the basic characteristics of the core flow field of the hydrocyclone do not change essentially with the increase in the number of cone segments, but the amplitude, distribution, and stability of flow field parameters are significantly regulated. The three-cone configuration achieves the optimal flow field synergy effect: the amplitude of the high turbulence intensity zone is lower and concentrated near the central axis; the zero-velocity envelope surface is stably maintained at approximately 8 mm in the core separation zone; and the full axial fluctuation of the air core is gentle, which effectively inhibits random particle diffusion and flow pattern mixing. In terms of separation performance, the three-cone configuration exhibits the highest classification efficiency in the core range of sub-coarse particles (10~30 μm), with the cut size (approximately 17.5 μm) in a reasonable range, the steepness index reaching a peak value (approximately 0.55), and the pressure drop (approximately 1.8 × 10⁵ Pa) and split ratio (2.8%) achieving synergistic optimization, balancing separation accuracy and energy consumption control. The single-cone configuration causes flow field disturbance due to the one-time contraction of the flow channel, while the four-cone configuration falls into the dilemma of “high pressure drop–marginal performance gain”, and neither achieves optimal performance. The regulation law of the number of cone segments revealed in this study provides a scientific basis for the structural optimization and engineering application of multi-cone hydrocyclones, and is of great significance for improving the particle classification efficiency in fields such as wastewater treatment and mineral processing. Full article

Neuroblastoma (NB) represents a paradigmatic developmental malignancy in which lineage specification, oncogenic signalling, and epigenetic regulation converge to define tumour behaviour. Among the molecular axes shaping NB heterogeneity, neurotrophin receptors of the tropomyosin receptor kinase (Trk) family (TrkA, TrkB, and TrkC) and the p75NTR occupy a central position at the intersection between neuronal differentiation programs and malignant plasticity. While high TrkA and TrkC expression is associated with adrenergic identity, differentiation competence, and favourable clinical outcome, TrkB, frequently sustained by BDNF-driven autocrine loops, characterises mesenchymal-like, therapy-resistant states enriched in metabolic and inflammatory adaptations. Importantly, in NB, the dysregulation of neurotrophin signalling rarely arises from recurrent genetic alterations of neurotrophic tyrosine receptor kinase (NTRK) loci. Instead, Trk receptor expression is dynamically shaped by promoter methylation, polycomb repressive complex 2/Enhancer of Zeste homolog 2 (PRC2/EZH2)-dependent chromatin repression, MYCN-driven transcriptional silencing, enhancer rewiring, and microRNA-mediated control. These epigenetic mechanisms govern reversible transitions along the adrenergic–mesenchymal (ADRN–MES) continuum, enabling tumour cells to adapt to microenvironmental and therapeutic stress. Single-cell and spatial multi-omics approaches have further revealed that Trk-associated phenotypes are embedded within complex regulatory circuits integrating receptor tyrosine kinase (RTK) networks, cytokine signalling, metabolic remodelling, and stromal reinforcement. Here, we provide a comprehensive synthesis of the epigenetic and microenvironmental mechanisms regulating neurotrophin receptors in NB, with particular emphasis on how chromatin plasticity and cell-state transitions reshape Trk-dependent signalling outputs. We discuss advanced three-dimensional and organoid-based models that recapitulate niche-specific regulation of the Trk axis and evaluate emerging therapeutic strategies combining epigenetic modulators, differentiation-inducing agents, and RTK-targeted compounds. Understanding the temporal and spatial dynamics of Trk signalling may open new opportunities to therapeutically stabilise differentiation states and disrupt adaptive resistance programs in high-risk NB. Full article

Microwave imaging is emerging as an alternative to conventional medical diagnostic techniques. Traditional analytical and numerical methods fail to adequately address these fundamental challenges: they often rely on strict linear approximations or simplified physical models, leading to low reconstruction accuracy, poor robustness, and limited generalization ability in complex clinical scenarios. As a result, they cannot meet the high-precision requirements of practical stroke microwave imaging. To further improve the accuracy of microwave imaging algorithms in recognizing stroke regions and solving the backscattering problem, this study employs a combination of methods with deep learning. It presents the Multi-Scale Attention Network (MSA-Net) for microwave imaging. The network is based on the EGE-UNet network structure with improved multi-axis Hadamard attention, incorporating null-space pyramid pooling and introducing a deep supervisory mechanism to improve the network performance further. To combine microwave imaging with deep learning, firstly, a large amount of microwave data need to be simulated with HFSS, in which the simulation model is a human brain stroke model constructed by an HFSS simulation system. Secondly, the microwave data obtained from the simulation are converted into a tensor format. Then, the tensor data are input into the MSA-Net neural network, which generates a binary mask image that can be used to detect the size and location of the stroke. This study also prompts the model to converge faster by sparsifying the microwave data to improve training efficiency. The method has been tested using simulation data, and based on the comparison experiments with other networks, MSA-Net is more accurate in detecting the location and the bleed size. The experimental results show that the proposed method is superior for stroke imaging. The experimental results show that the proposed model achieves a 1.08 improvement in peak signal-to-noise ratio and a 0.017 reduction in learned perceptual image block similarity, fully validating the effectiveness of the structural optimization strategy proposed in this paper. Full article

Nitric oxide (NO) functions as a master integrative regulator of cardiovascular–kidney–metabolic (CKM) homeostasis, yet it displays a profound Janus face, defined by concentration- and context-dependent roles in both health and disease. This narrative review examines NO signaling from a life-course perspective, beginning with fetal programming, during which the NO–asymmetric dimethylarginine (ADMA) axis orchestrates placental development and nephron endowment. Perturbations during this critical window—such as maternal ADMA elevation—can imprint a maladaptive trajectory toward adult-onset hypertension and chronic kidney disease. In adulthood, this initially silent dysregulation of NO signaling is amplified by Western dietary patterns and environmental pollutants, culminating in the clinical manifestation of the CKM triad. This pathological transition is driven by eNOS uncoupling and ADMA accumulation, which shift redox balance toward peroxynitrite formation and precipitate mitochondrial bioenergetic failure. Moreover, while constitutive NO production is essential for vascular homeostasis, pathological induction of inducible NOS generates excessive NO fluxes that promote insulin resistance and tissue injury. With advancing age, a progressive loss of NO resilience further exacerbates multi-organ vulnerability. To mitigate the cumulative burden of CKM disease, this review highlights developmental reprogramming strategies—such as perinatal L-citrulline supplementation and ADMA-lowering interventions—as interventions to restore physiological NO signaling. Integrating such early-life strategies with contemporary pharmacological therapies offers a coherent framework for maintaining NO bioavailability and extending health span across the life course. Full article

Background: Psoriasis is a chronic immune-mediated inflammatory disease with a strong genetic basis, driven in part by the dysregulation of the IL-23/Th17 signaling axis. Variants in the IL23R and IL12B genes have been associated with psoriasis susceptibility; however, data from Eastern European populations remains scarce. Objective: We aimed to evaluate the link between IL23R rs11209026 and IL12B rs3213094 polymorphisms and psoriasis susceptibility in a multi-center, Romanian cohort. Methods: We performed a multi-center case–control study including adult patients with clinically and histopathologically confirmed moderate-to-severe psoriasis undergoing biological therapy and controls without autoimmune or chronic inflammatory diseases. Genotyping was performed using TaqMan SNP assays. Associations were analyzed under a dominant genetic model. Results: A significant association was observed between IL23R rs11209026 polymorphism and psoriasis susceptibility. Carriers of the A allele (AA+GA) showed reduced odds of psoriasis compared with the GG homozygotes, emphasizing the protective effect of this specific variant. No significant association was identified for IL12B rs3213094 polymorphism. Conclusions: Our findings support the protective association of IL23R rs11209026 A allele with psoriasis in a Romanian Eastern European population and emphasize the importance of the IL-23 pathway in disease pathogenesis. Alcohol consumption was independently associated with increased risk of psoriasis. Further studies are justified to explore potential pharmacogenetic implications. Full article

The Bond Graph (BG) methodology, a multi-domain graphical description formalism, is used to study a horizontal-axis two-mass drive train of a wind turbine. The main contribution of this work is to address the lack of wind energy literature dealing with fully unambiguous, traceable, and dimensionally homogeneous per-unit quantities for two-mass drive train models. Data in real quantities for the drive train are collected from open-access datasheets and their corresponding design information files. Wind turbines that may serve as Reference Wind Turbines (RWTs), with traceable calculations, are carefully selected. A lumped-parameter order-reduction method is employed to convert data from higher-order models into data for a reduced-order two-mass model. The BG methodology is then used to formally derive the per-unit drive train model and its corresponding dimensionally homogeneous per-unit parameters for a set of six representative Reference Wind Turbines, covering a nominal power range from 0.75 MW to 5 MW. Full article

Laser powder bed fusion (LPBF) technology has now reached a significant level of commercial maturity, offering some of the most reliable solutions in the additive manufacturing (AM) field. However, AM processes may introduce defects that result in high variability of mechanical properties and low reproducibility. This entails the need to thoroughly understand the behavior of the materials used, studying their response to the different types of stresses typical of real-world applications. The research activity presented consists of the analysis of the mechanical properties of the aluminum alloy AlSi10Mg, which is widely used due to its good strength-to-density ratio. Focus is put on the response to axial, torsional, and combined axial-torsional static and fatigue strength, comparing as-built T6 heat-treated conditions. Full article