Search Results (5,144)

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: 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

Addressing the prevalent issue of “physical preservation but spiritual silence” in the revitalisation of China’s national industrial heritage, this study proposes and empirically validates a “dual-track narrative” design framework that systematically translates cultural values into spatial experiences. The framework integrates a “figure–history” narrative, which crystallises historical lineage and symbolic spirit through spatial sequences, commemorative landmarks, and authentic remains, with a “scene–activity” narrative, which transforms former production spaces into dynamic, culturally vibrant stages through ecological restoration displays, industrial landscape transformation, and flexible activity implantation. Using Nantong Guangsheng Oil Mill as a single-case study, the research employs qualitative methods including archival analysis, field observation, and semi-structured interviews to examine how the dual-track framework operates in practice. The findings reveal that the “figure–history” narrative manifests in a walkable “time corridor” along the north–south axis, where architectural remnants from different eras are organised to materialise Zhang Jian’s industrial salvation ethos and the collective memory of generations of workers. Meanwhile, the “scene–activity” narrative activates underutilised spaces—such as the repurposing of acid treatment ponds into constructed wetlands and paved grounds into public stages—enabling ongoing cultural production, community interaction, and ecological healing. The study demonstrates that the dual-track framework bridges the historical and contemporary dimensions often treated separately in heritage practice, establishing a systematic “translation mechanism” from cultural decoding to design intervention. Theoretically, it contributes to industrial heritage research by integrating narratology, memory studies, heritage interpretation, and situationism into a coherent design methodology. Practically, it offers decision-makers evaluation criteria beyond the preservation-versus-development binary, provides designers with a mode of creative transformation grounded in material authenticity, and suggests to operators a content-driven, event-based model for sustaining heritage spaces. By spatialising and eventising narratives, the dual-track approach enables industrial heritage to function as a catalyst for cultural identity, social vitality, and economic sustainability, offering a transferable paradigm for the adaptive reuse of industrial heritage in contemporary urban contexts. Full article

Background/Objectives: Modern diabetes therapy extends beyond glycemic control and increasingly focuses on comprehensive risk reduction to prevent long-term complications, improve quality of life, and reduce premature mortality. Accordingly, modern therapeutic approaches address not only glucose metabolism but also cardiovascular, renal, and metabolic consequences of diabetes. Within this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a significant therapeutic class. In addition to their well-known effects on glycemic control and the metabolic-cardiovascular-renal axis, increasing evidence suggests that these agents may exert a range of pleiotropic effects and opening new therapeutic venues, discussed in this review. Methods: A narrative review of the literature was conducted using the PubMed, Scopus, and Google Scholar databases. Publications from 2014 and 2026 were screened using predefined keywords related to GLP-1 RAs and their potential effects across multiple physiological systems and diseases. Notably, more than 80% of the included studies were published between 2020 and 2026, reflecting the recent growth of research in this field. Results: GLP-1 RAs have been associated with beneficial effects across a wide range of conditions, including substance use disorders, mental health disorders, neurodegenerative diseases, obesity-related complications, liver disease, genitourinary disorders, osteoarthritis, and sleep apnea. While they are currently the most effective pharmacological agents for the treatment of obesity, they also significantly reduce hepatic steatosis and are associated with a decreased risk of developing hepatocellular carcinoma. Furthermore, they have also demonstrated positive effects against prostate cancer, polycystic ovary syndrome (PCOS), improved libido and fertility. Conclusions: GLP-1 RAs should no longer be regarded solely as antihyperglycemic agents. Instead, they represent a versatile therapeutic class with expanding clinical relevance across multiple medical disciplines. While current evidence is promising, further large-scale, well-designed clinical trials are required to define their full therapeutic potential. 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

Lateral wear inevitably develops on the wheel treads of high-speed trains after a period of operation. Extensive research has been dedicated to circumferential wear (e.g., wheel polygonization), whereas studies on lateral tread wear and its impact on wheel-rail noise remain limited. This study investigates this issue through a combined approach of field measurements and numerical simulation. First, lateral wear profiles are measured on in-service high-speed train wheels, and their patterns are systematically analyzed. Subsequently, a three-dimensional transient wheel-rail rolling contact model is developed using the explicit finite element method. This model is employed to analyze the effects of the lateral hollow wear depth on the contact patch position and wheel-rail forces at 400 km/h. Finally, these calculated forces are imported into a coupled wheel-rail vibration and acoustic radiation model to predict noise characteristics at different wear depths. This study clarifies the coupling of lateral tread hollow wear with wheel-rail contact characteristics at 400 km/h and quantifies its mechanical influence on high-frequency wheel-rail noise via contact patch evolution and structural receptance variation. The results demonstrate that lateral wear manifests as hollow wear, with a maximum depth of approximately 1 mm within a reprofiling cycle. It has been found that as the hollow wear depth increases, the contact patch center shifts toward the wheel flange, and its major axis elongates. Consequently, wheel-rail noise increases significantly with greater wear depth. Specifically, a wear depth increase of 0.78 mm leads to increments of 2.3 dB in wheel noise, 0.9 dB in rail noise, and 1.0 dB in total wheel-rail noise. These findings underscore that tread hollow wear is a significant contributor to high-speed wheel-rail noise, highlighting the need for its consideration in maintenance and noise control strategies. Full article

Vascular remodeling driven by the phenotypic switching of vascular smooth muscle cells (VSMCs) poses a significant health risk to astronauts during long-duration spaceflight. While the morphological and molecular changes are well recognized, the underlying metabolic drivers and potential translational countermeasures remain elusive. To investigate the metabolic determinants of VSMCs phenotypic switching, human aortic smooth muscle cells (HASMCs) were subjected to cyclic mechanical stretch, an in vitro model offering indirect mechanistic insights into mechanical loading conditions relevant to spaceflight-associated hemodynamic alterations. An integrated approach combining quantitative proteomics, flux analysis (Seahorse), and functional assays (cell cycle, wound healing, transwell) was used to characterize the accompanying metabolic and phenotypic alterations. Molecular mechanisms were assessed using immunoprecipitation, protein crosslinking, and immunofluorescence. Mechanical stretch triggered a contractile-to-synthetic phenotypic switch in HASMCs, accompanied by a shift from oxidative phosphorylation to aerobic glycolysis. Pyruvate kinase M2 (PKM2) was identified as a central metabolic regulator of this process, its silencing reversed the pro-synthetic phenotype. Notably, lactate, a glycolytic product, was found to exert a self-limiting feedback signal. Exogenous lactate suppressed the synthetic switch in associated with increased PKM2 lactylation. Further analysis indicated that PKM2 lactylation was associated with enhanced stability of its active tetrameric conformation, which was associated with a metabolic shift toward oxidative phosphorylation and restored expression of contractile markers. Although specific lactylation sites on PKM2 were not identified in this study, and direct causality between lactylation and tetramerization remains to be established, these findings identify a previously unrecognized association. This study reveals a novel metabolic regulatory mechanism in which lactate correlates with the suppression of synthetic switching of VSMCs, linked to PKM2 lactylation and tetramer stabilization. The observed lactate-PKM2 axis represents a candidate metabolic node associated with VSMCs phenotype regulation and offers a potential therapeutic target for modulating vascular remodeling. Upon direct validation under relevant conditions in future studies, this mechanism may inform the development of novel therapeutic strategies for managing vascular adaptation during long-duration spaceflight and other aerospace-related physiological challenges. Full article

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway serves as a central innate immune signaling axis in host defense against DNA virus infections, and RNA viruses have also evolved diverse strategies to counteract this pathway. Encephalomyocarditis virus (EMCV), a zoonotic RNA virus, utilizes its 2C protein to antagonize RIG-I-like receptor-mediated type I interferon signaling and induce autophagic degradation of calcium binding and coiled-coil domain 2, thereby evading host antiviral immunity. However, the precise molecular mechanism by which EMCV 2C protein modulates the cGAS-STING pathway remains incompletely understood. Herein, we show that EMCV infection reduces the expression of cGAS and STING proteins, and its 2C protein significantly suppresses the production of IFN-β triggered by poly(dA:dT) or viral infection, as well as the mRNA expression of interferon-stimulated genes. Mechanistically, 2C protein binds to STING via its ATPase domain and facilitates K48-linked polyubiquitination and proteasomal degradation of STING, while dominantly interfering STING translocation to the Golgi apparatus and the formation of STING-TBK1-IRF3 complex, thereby blocking STING-mediated IFN-β signal transduction at multiple levels. This study reveals a novel mechanism by which the EMCV 2C protein suppresses the host antiviral response by targeting STING and promoting its ubiquitination and degradation. This finding deepens understanding of the immune evasion mechanism of EMCV and provides a theoretical foundation for the development of antiviral therapies targeting the 2C protein of picornaviruses. Full article

Homeobox (HOX) transcription factors are encoded within highly organized loci expressed along an anterior–posterior axis through embryogenesis and in a pleiotropic manner in hematopoiesis. HOX expression has been exhaustively studied in the context of oncogenesis and malignancy, but the compensatory substitution of HOX paralogs makes mechanistic annotation in steady-state hematopoiesis challenging. Despite this, HOX genes reflect numerous non-redundant roles in healthy hematopoiesis including HSC self-renewal, development, lymphopoiesis, myelopoiesis, and erythropoiesis. Here, we review historical and current insights into HOX functions in steady-state hematopoiesis and highlight unexplored avenues in their biology that could further elucidate their significance to hematopoietic homeostasis. Full article

Nuclear lamins are the core molecular bridge linking the extracellular mechanical microenvironment to intranuclear gene regulation, and play a central regulatory role in cellular mechanosensation and mechanotransduction. Here, we systematically integrate the latest global research progress on nuclear lamins, delineating the cascade regulatory mechanism by which lamins mediate the transmission of mechanical signals across the nuclear envelope and the subsequent regulation of chromatin remodeling and epigenetic modification, with a focus on the molecular characteristics and functional specificity of distinct nuclear lamin subtypes and their interaction modes with the Linker of Nucleoskeleton and Cytoskeleton complex (LINC complex) and chromatin. Existing studies have established that nuclear lamins are mainly divided into three categories: A-type lamins (Lamin A/C), B-type lamins (Lamin B1, B2), and germ cell-specific subtypes. Among these, A-type lamins directly determine the mechanical stiffness of the nucleus and serve as the core mediators of intranuclear mechanical signal transduction. Each subtype of B-type nuclear lamins has a well-defined, non-redundant functional division: Lamin B1 and Lamin B2 indirectly maintain nuclear structural stability and regulate epigenetic status by anchoring facultative heterochromatin and constitutive heterochromatin, respectively. Notably, Lamin A/C distributed in the nucleoplasm also bears significant mechanical tension, which challenges the long-standing view that the mechanical functions of nuclear lamins are restricted to the nuclear envelope region. After mechanical force is transmitted across the nuclear envelope to nuclear lamins via the LINC complex, it can regulate the spatial conformation of chromatin and epigenetic modifications, thereby determining core cellular life activities including proliferation, differentiation, and migration. Dysregulation of this pathway is closely associated with a wide spectrum of human diseases, including cardiovascular diseases, progeria, muscular dystrophy, and neurodevelopmental disorders. Taken together, this review systematically delineates the hierarchical regulatory network of the “LINC complex–nuclear lamina–chromatin” axis, advances our understanding of the fundamental principles of cellular mechanobiology, and provides a theoretical framework for deciphering the pathological mechanisms and developing targeted therapeutic drugs for related diseases. Full article

Dynamic Wireless Power Transfer (DWPT) represents a promising solution to advance sustainable electric mobility by reducing vehicle downtime, extending driving range, and mitigating the need for battery oversizing. However, the lack of integrated and flexible experimental testbeds still limits the validation of emerging technologies. This paper presents DEXTER (Development of an Enhanced eXperimental proTotype of wirEless chargeR), a 1:2-scale open platform specifically designed for research on DWPT systems. The setup integrates a three-axis motion control for coil misalignments and trajectory emulation, digitally regulated TX/RX converters, a programmable battery emulator, and electromagnetic shielding coils equipped with field probes. A MATLAB-based interface enables automated testing and Hardware-in-the-Loop (HiL) integration. By combining modularity, scalability, and reproducibility, DEXTER provides a comprehensive framework for experimental optimization of power electronics and electromagnetic design while ensuring compliance with international safety standards. The case studies analyzed here demonstrate the capability of such a platform to validate and optimize the DWPT design choices, checking their impact on the overall performance of these systems. The platform constitutes a reference environment for both academia and industry, supporting the development of next-generation wireless charging systems and contributing to the sustainability and reliability of future electric mobility infrastructures. Full article

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies. Full article

The selection of deformation mechanisms in hexagonal close-packed (HCP) metals is strongly influenced by both crystallographic orientation and macroscopic deformation constraints. In commercially pure titanium, plastic deformation under constrained loading conditions involves a complex interplay between dislocation slip and deformation twinning, whose respective activation cannot be fully described by classical stress-based criteria. In this study, the mechanical origin of slip and twinning variant selection in commercially pure titanium subjected to plane strain compression is investigated experimentally. Plane strain compression is used as a canonical loading condition representative of constrained deformation paths encountered in sheet metal forming. Interrupted in-situ electron backscatter diffraction is combined with slip trace and twin variant analyses to identify the active deformation mechanisms at the grain scale. Resolved shear stress calculations show that stress-based criteria provide a necessary first-order condition for the activation of both slip and twinning systems. While the Schmid factor reasonably predicts part of the observed slip activity, it fails to uniquely determine the selection of active twinning variants. A kinematic analysis reveals that twinning variant selection is governed by the compatibility between the deformation induced by twinning and the macroscopic strain constraints imposed by plane strain compression. Only variants whose deformation accommodates compression along the loading axis, extension along the free in-plane direction, and minimal strain along the constrained in-plane direction are preferentially activated. These results demonstrate that deformation mechanism selection in HCP titanium under constrained loading conditions results from a combined effect of resolved shear stress and kinematic compatibility. The proposed framework provides a physically grounded basis for interpreting deformation-induced texture evolution and offers clear perspectives for the development of crystal plasticity models incorporating twinning under complex strain paths. Full article

Chronic stress is defined as a prolonged state of emotional disturbance and psychological strain resulting from an inability to maintain internal homeostasis. It is recognized as a significant risk factor for breast cancer, primarily through the chronic activation of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis. This neuroendocrine activation leads to elevated systemic levels of epinephrine, norepinephrine, and glucocorticoids. By binding to their respective adrenergic and glucocorticoid receptors, these hormones disrupt immune homeostasis and exacerbate oxidative stress within the tumor microenvironment. Such physiological shifts promote critical oncogenic processes, including angiogenesis and tumor cell proliferation, thereby driving the development, progression, and distant metastasis of breast cancer. Mastication, or the act of chewing, serves as a practical and effective behavioral strategy for modulating the deleterious effects of chronic psychological stress. Recent animal studies have provided compelling evidence that chewing can attenuate excessive stress responses. Specifically, it has been shown to mitigate stress-induced breast cancer progression and metastasis by modulating the expression of stress hormones, their corresponding receptors, and key downstream signaling pathways. These findings suggest that the rhythmic activity of chewing may exert a protective effect against stress-related tumor exacerbation. Consequently, further clinical research is warranted to determine whether chewing interventions can serve as a viable complementary strategy alongside conventional breast cancer prevention and treatment protocols. Full article