Search Results (4,205)

Background/Objectives: Type 1 diabetes (T1D) is a common childhood condition with rising global incidence. Because early-onset T1D coincides with key periods of brain maturation, affected children may face neurocognitive risks. This review summarizes current evidence on the neurocognitive impact of pediatric T1D and related clinical implications. Methods: A structured search of PubMed, Scopus, and Web of Science (inception–October 2025) used combinations of terms related to T1D, cognitive outcomes, and brain imaging. Studies involving participants under 18 years that reported cognitive or neuroimaging findings were included. Results: Diabetic ketoacidosis (DKA) at diagnosis is consistently linked with acute and longer-term neurological injury, including reduced brain volume and potential persistent deficits in memory and executive functioning. Severe or recurrent hypoglycemia disproportionately affects the hippocampus, contributing to lasting learning and memory impairments. Chronic hyperglycemia is a major driver of progressive neurocognitive decline; higher HbA1c is associated with smaller brain volumes and poorer executive function, attention, and processing speed. Early-onset disease and longer duration further increase vulnerability. These neurocognitive effects translate into modest reductions in academic performance and quality of life, especially with poor glycemic control. Emerging evidence suggests that continuous glucose monitoring, insulin pumps, and hybrid closed-loop systems improve metabolic stability and may support healthier brain development. Conclusions: T1D children experience subtle but meaningful neurocognitive risks shaped by glycemic extremes and early disease onset. Routine neuropsychological monitoring, strengthened academic support, and wider use of advanced diabetes technologies may help preserve cognitive development. Larger, longitudinal neuroimaging studies are needed to guide targeted neuroprotective strategies. Full article

Background/Objectives: Infectious disease outbreaks are recurring global crises that particularly impact older adults, who are vulnerable both biologically and psychosocially. Older adults living in the community, often depending on informal support rather than institutional care, may be especially at risk during extended outbreaks. This study examined psychosocial predictors of anxiety and depression with a focus on the novel integration of multidimensional infectious-disease-related stress and differentiated functional pathways of social support. Methods: A cross-sectional survey involved 178 community-dwelling adults aged 65 and older in South Korea. Validated tools measured anxiety (K-GAI), depression (K-GDS-SF), infectious disease-related stress (fear of infection, anger toward others, and social distancing difficulties), social support (emotional, informational, material, and appraisal), and chronic illness status. Data analysis included correlation analyses and stepwise multiple regression. Results: Difficulties adhering to social distancing were the strongest stress-related predictor of both anxiety and depression, while emotional support emerged as the most powerful protective factor against both outcomes. Material support uniquely mitigated depressive symptoms, and older adults with chronic illness showed heightened vulnerability to depression. Conclusions: Infectious-disease-related stress is multidimensional, extending beyond fear of infection to include social-participation disruption and relational strain. Findings highlight that different types of social support exert distinct protective effects through function-specific mechanisms, reinforcing the importance of targeted intervention design. Practical implications include strengthening emotional-support infrastructure, implementing hybrid digital–offline outreach models, and prioritizing resource allocation for medically vulnerable older adults as part of preparedness planning for future prolonged public-health emergencies. Full article

Pulmonary hypertension (PH) is a progressive and life-threatening disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular remodeling and significant mortality. Pulmonary arterial remodeling, a critical pathological feature of PH, refers to structural alterations in the pulmonary vasculature driven by various pathogenic factors. Targeting this remodeling process has emerged as a promising strategy for treating and potentially curing the disease. In recent years, growing interest has been directed toward exploring natural products as anti-PH agents. Among them, flavonoids have demonstrated potent efficacy in the cardiopulmonary system. As a prominent class of natural small-molecule compounds, flavonoids exhibit broad biological activities, such as antioxidant, anti-inflammatory, and anti-proliferative properties. They have shown the ability to inhibit remodeling and restore vascular function across various vessel types, including pulmonary arteries. This review summarizes the effects of flavonoids on PH, with emphasis on their inhibition of pulmonary arterial remodeling. We also discuss the therapeutic potential of flavonoids in PH and discuss their underlying mechanisms of action. These insights may guide the development of next-generation PH therapeutics, either through the utilization of flavonoid-based structures or the preparation of compound formulations containing flavonoids. Full article

RNA-binding proteins (RBPs) play a pivotal role in post-transcriptional gene regulation, influencing various cellular processes, including development, differentiation, and disease progression. Emerging evidence suggests that RBPs function as critical modulators of the canonical Wnt signaling pathway, a key regulator of cell fate determination, proliferation, and tumorigenesis. By controlling the stability, localization, and translation of Wnt pathway components, RBPs fine-tune the dynamic signaling responses necessary for maintaining cellular homeostasis. Several RBPs have been identified as direct regulators of key components in the Wnt cascade, such as IGF2BP1, HuR, and MSI1, impacting their expression and activity. Dysregulation of these RBPs has been linked to aberrant Wnt signaling, contributing to various pathological conditions such as cancers or developmental disorders. This review explores the emerging landscape of RBPs in the regulation of canonical Wnt signaling, highlighting their molecular mechanism, functional implications, and potential as therapeutic targets in Wnt-driven disease. Full article

The cellular prion protein (PrP^C) displays a functional repertoire that extends well beyond its classical link to transmissible spongiform encephalopathies. Abundant in the nervous system and localized within lipid raft microdomains, PrP^C has emerged as a multifunctional signaling platform that regulates cell differentiation, neurogenesis, neuroprotection, and synaptic plasticity. Recent evidence highlights its dynamic expression in stem cell populations, where it participates in multimolecular complexes that control lineage commitment, particularly during neuronal differentiation. PrP^C expression tightly correlates with stem cell status, making it a promising biomarker of stemness and developmental progression. Through interactions with growth factors, extracellular matrix components, and synaptic proteins, PrP^C functions as a molecular integrator of signals essential for tissue repair and regeneration. Preclinical studies demonstrate that recombinant PrP^C can stimulate neurogenesis and tissue repair, while monoclonal antibodies modulate its physiological and pathological functions. Likewise, cell-based therapies leveraging PrP^C-enriched stem cells or PrP^C-dependent signaling profiles have shown promise in models of neurodegeneration and ischemia. Conversely, dysregulated PrP^C expression has also been observed in solid tumors, where it contributes to cancer cell survival, proliferation, metastasis, and therapy resistance, reinforcing its role as a regulator of cell fate and an oncological target. This review integrates stem cell biology, tissue regeneration, and oncology into a unified framework, offering a novel perspective in which PrP^C emerges as a shared molecular hub governing both physiological repair and pathological tumor behavior, opening previously unrecognized conceptual and translational opportunities. Full article

Sensory systems allow the detection of external and internal cues essential for adaptive responses. Chemosensation exemplifies this integration, guiding feeding, mating, and toxin avoidance while also influencing physiological regulation. Across taxa, chemical detection relies on diverse receptor families, and emerging evidence reveals that transient receptor potential (TRP) channels—traditionally associated with phototransduction, thermosensation, and mechanotransduction—also mediate chemosensory functions. Studies in Drosophila melanogaster and vertebrates demonstrate that TRPs detect tastants, odorants, and internal chemical states, highlighting their evolutionary conservation and functional versatility. This review synthesizes current insights into the roles of TRP channels across four major domains: taste, smell, internal state, and central circuit modulation. Using D. melanogaster and mammalian systems as comparative frameworks, we highlight how TRP channels function as polymodal sensors, signal amplifiers, and modulators embedded within canonical receptor pathways rather than as standalone chemoreceptors. Recognizing these integrative functions not only expands our understanding of how organisms coordinate behavior with internal states but also points to TRP channels as potential targets for addressing chemosensory disorders and metabolic diseases. This framework highlights key directions for future research into TRP-mediated sensory and homeostatic regulation. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with heart failure (HF) representing a major contributor to hospitalizations, healthcare costs, and death. Effective management of HF is hindered by the limitations of current biomarkers and diagnostic tools. Conventional biomarkers, such as natriuretic peptides, primarily reflect downstream hemodynamic stress and often lack specificity, particularly in HF with preserved ejection fraction or multiple comorbidities. While imaging provides valuable structural and functional information, it is resource-intensive, costly, and unsuitable for frequent longitudinal monitoring. As a result, these conventional approaches are inadequate to capture the dynamic and heterogeneous nature of HF pathophysiology. Circulating cell-free nucleic acids (cfNAs), including cell-free DNA (cfDNA) and RNA (cfRNA), have emerged as promising noninvasive liquid biopsy biomarkers capable of providing real-time insight into upstream pathological events, such as cardiomyocyte injury, immune activation, inflammation, and maladaptive remodeling. Importantly, cfNAs also act as active mediators of CVD pathology. When released under stress or injury, cfNAs interact with pattern recognition receptors (PRRs) that trigger sterile inflammation, cardiovascular cell dysfunction, and adverse cardiac remodeling. This review summarizes the origins, mechanistic roles, and clinical significance of cfNAs in HF and related CVD, highlighting their dual roles as diagnostic biomarkers and mechanistic effectors of disease. Finally, we discuss emerging cfNA-targeted therapeutic strategies, challenges, and future opportunities for precision medicine in HF and HF-associated CVD. Full article

In arid regions, rainfall is scarce, summer-concentrated, and prone to extreme events, while evaporation exceeds precipitation, creating fragile ecosystems that need scientific stormwater management for flood resilience. Sponge cities, through the implementation of green infrastructure, can alleviate urban flooding, improve rainwater utilization, and enhance the urban ecological environment. Under the “dual carbon” target, sponge city construction has gained new developmental significance. It must not only ensure core functions and minimize construction costs but also fully leverage its carbon reduction potential, thereby serving as a crucial pathway for promoting urban green and low-carbon development. Therefore, this study focused on Xining, a typical arid city in Northwest China, and couples the Non-dominated Sorting Genetic Algorithm-III (NSGA-III) with the Storm Water Management Model (SWMM) to construct a multi-objective optimization model for Low Impact Development (LID) facilities. The layout optimization design of LID facilities is conducted from three dimensions: life cycle cost (LCC), rainwater utilization rate (K), and carbon emission intensity (CI). Hydrological simulations and scheme optimizations were performed under different design rainfall events. Subsequently, the entropy-weighted TOPSIS method was utilized to evaluate and compare these optimized schemes. It is shown by the results that: (1) The optimized LID schemes achieved a K of 76.2–80.43%, an LCC of 2.413–3.019 billion yuan, and a CI of −2.8 to 0.19 kg/m²; (2) Compared with the no-LID scenario, the optimized scheme significantly enhanced hydrological regulation, flood mitigation, and pollutant removal. Under different rainfall return periods, the annual runoff control rate increased from 64.97% to 80.66–82.23%, with total runoff reduction rates reaching 46.41–49.26% and peak flow reductions of 45–47.62%. Under the rainfall event with a 10-year return period, the total number of waterlogging nodes decreased from 108 to 82, and the number of nodes with a ponding duration exceeding 1 h was reduced by 62.5%. The removal efficiency of total suspended solids (TSS) under the optimized scheme remained stable above 60%. The optimized scheme is highly adaptable to the rainwater management needs of arid areas by prioritizing “infiltration and retention”. Vegetative swales emerge as the primary facility due to their low cost and high carbon sink capacity. This study provides a feasible pathway and decision-making support for the low-carbon layout of LID facilities in arid regions. Full article

Vascular diseases (VDs) and cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. Current diagnostic and therapeutic approaches are limited by insufficient resolution and a lack of mechanistic understanding at the cellular level. Traditional imaging and clinical assays do not fully capture the dynamic molecular and structural complexities underlying vascular pathology. Recent technological innovations, including single-cell and spatial transcriptomics, super-resolution and photoacoustic imaging, microfluidic organ-on-chip platforms, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene editing, and artificial intelligence (AI), have created new opportunities for investigating the cellular and molecular basis of VDs. These techniques enable high-resolution mapping of cellular heterogeneity and functional alterations, facilitating the integration of large-scale data for biomarker discovery, disease modeling, and therapeutic development. This review focuses on evaluating the translational readiness, limitations, and potential clinical applications of these emerging technologies. Understanding the cellular and molecular mechanisms of VDs is essential for developing targeted therapies and precise diagnostics. Integrating single-cell and multiomics approaches highlights disease-driving cell types and gene programs. Optogenetics and organ-on-chip platforms allow for controlled manipulation and physiologically relevant modeling, while AI enhances data integration, risk prediction, and clinical interpretability. Future efforts should prioritize multi-center, large-scale validation studies, harmonization of assay protocols, and integration with clinical datasets and human samples. Multi-omics approaches and computational modeling hold promise for unraveling disease complexity, while advances in regulatory science and digital simulation (such as digital twins) may further accelerate personalized medicine in vascular disease research and treatment. Full article

Developing precise tumor-targeting delivery systems while minimizing off-target toxicity continues to pose significant challenges in medicine application. The integration of two different functional materials has emerged as a promising strategy in current biomedical research. Herein, a hybrid nanocomposite consisting of Fe₃O₄ and ZnO was synthesized via a simple approach and employed as a nanoscale drug delivery system to explore the loading capacity and stimuli-responsive release characteristics of the anticancer agent doxorubicin (DOX). Results show that the synthesized nanoparticles (NPs) exhibit a multi-scale nanostructure consisting of the spindle-like ZnO nanorods with a mean length of 280 nm, on which the Fe₃O₄ NPs with a diameter of around 16 nm are uniformly dispersed. The ZnO@Fe₃O₄ NPs possess superparamagnetic behavior and a fast response to the external magnet and demonstrate exceptional near-infrared (NIR) photothermal conversion efficiency. In drug release studies, the ZnO@Fe₃O₄ NPs achieve the controlled DOX release in the simulated acidic tumor microenvironment as well as NIR laser irradiation. Further, the ZnO@Fe₃O₄-DOX composites significantly suppress the viability of human cervical cancer cells (HeLa) upon laser activation. These findings suggest that ZnO@Fe₃O₄ NPs are promising candidates for combined photothermal therapy, magnetic-targeted drug delivery, and stimuli-responsive controlled release applications. Full article

Dietary fiber is an essential component of the human diet, and insoluble dietary fiber (IDF) accounts for a significant proportion. However, its poor solubility and rigid structure limit its high-value applications. In recent years, modification technologies have become key strategies for enhancing the functional properties of IDF and expanding its applications. This review systematically summarizes the latest advances in the field of IDF modification, emphasizing how different modification strategies precisely regulate the multilevel structure of IDF to selectively improve its physicochemical properties and physiological functions. The principles and mechanisms of physical, chemical, biological, and combined modification methods are explained, and the unique advantages and limitations of each method in terms of structural changes, functional enhancement, and application scenarios are compared. Using high-pressure hydrostatic pressure-assisted cellulase treatment on potato dietary fiber can effectively disrupt fiber rigidity, increase soluble dietary fiber (SDF), and markedly enhance cholesterol and glucose adsorption capacities, outperforming single-treatment approaches. Microwave-assisted enzymatic treatment of millet bran IDF raises its intestinal fermentation rate from 36% to 59% and doubles butyrate production, significantly boosting prebiotic activity and offering a new pathway for targeted modulation of gut microbiota; combined modification strategies further demonstrate synergistic benefits. Modified IDF can serve not only as a low-calorie fat replacer in foods but also, through specific structural alterations, be incorporated into plant-based meat products to improve their fiber attributes and nutritional density. Moreover, this review explores the emerging potential of modified IDF in pharmaceutical carriers and gut microecology regulation. The aim is to provide theoretical guidance for selecting and optimizing IDF modification strategies, thereby promoting the high-value utilization of agricultural processing by-products and the development of high-quality dietary fiber products. Full article

Background: The insulin-like growth factor 2 receptor (IGF-2R), also known as the cation-independent mannose 6-phosphate receptor (CI-M6PR), is emerging as a critical receptor for brain function and disease. IGF-2R, in fact, plays a key role in long-term memory, and its activation by several ligands shows beneficial effects in multiple neurodevelopmental and neurodegenerative disease models. Thus, its targeting is very promising for neuropsychiatric therapeutic interventions. IGF-2R’s main known functions are transport of lysosomal enzymes and regulation of developmental tissue growth, but in the brain, it also controls learning-dependent protein synthesis underlying long-term memory. However, little is known about this receptor in brain cells, including its cell-type-specific and subcellular expression. Methods: We conducted a comprehensive investigation to comparatively assess IGF-2R protein levels in different brain cell types across various brain regions in adult male C57BL/6J mice using dual and multiplex immunofluorescent staining with cell-type-specific markers. The IGF-2R protein distribution was also compared with Igf2r mRNA expression in publicly available single-cell RNA sequencing databases. Results: A ranking of IGF-2R levels in the soma of various cell types in the hippocampus and cortical regions revealed that the highest enrichment is, by far, in excitatory and inhibitory neurons, followed by vascular mural cells and subpopulations of oligodendrocyte lineage cells, with low to undetectable levels in astrocytes, microglia, vascular endothelial cells, and perivascular fibroblasts. High levels of IGF-2R were also found in ependymal cells, choroid plexus epithelial cells, and a subpopulation of meningeal fibroblast-like cells. IGF-2R was found in dendritic and putative axonal compartments throughout the brain, with particularly high levels in the stratum lucidum. The receptor’s protein distribution aligned with that of the mRNA in mouse brain databases. Conclusions: These results suggest that IGF-2R-mediated functions in the brain vary across different cell types and subcellular compartments, with the most active roles in specific subpopulations of neurons, mural cells, ependymal cells, meningeal cells, and cells of the oligodendrocyte lineage. This study advances our understanding of IGF-2R’s distribution in the brain, which is essential for formulating new hypotheses about its functions and therapeutic targeting. Full article

Steatotic liver disease (SLD) represents a major global health burden, with environmental toxicants emerging as critical contributors alongside metabolic dysfunction. Bisphenol F (BPF), an increasingly prevalent replacement for bisphenol A, is widely detected in human biological samples and environment, yet its hepatotoxic mechanisms remain incompletely characterized. This review synthesizes current evidence on BPF-induced SLD, with a particular focus on resolving the “pregnane X receptor (PXR) paradox”, the mismatch between BPF’s weak direct activation of PXR and the PXR-like metabolic effects observed in vivo. Comprehensive analysis of mechanistic pathways reveals that BPF-induced SLD develops predominantly through PXR-independent mechanisms involving oxidative stress, endoplasmic reticulum dysfunction, Drp1-mediated mitochondrial fission, NLRP3/NF-κB-driven inflammation, dysregulated post-translational modifications, and epigenetic remodelling. These converging pathways collectively disrupt hepatic lipid metabolism, promote triglyceride accumulation, and establish a self-perpetuating cycle of metabolic dysfunction. Notably, weak indirect PXR modulation via oxidative stress represents a secondary, non-causal mechanism unsupported by functional validation. This framework distinguishes toxicant-induced steatosis from metabolic dysfunction-associated steatotic liver disease while highlighting critical evidence gaps—particularly the absence of causal PXR validation studies and human epidemiological data. Therapeutic opportunities exist at validated convergence points including mitochondrial dynamics (Drp1), inflammatory signalling (NLRP3/NF-κB), and energy metabolism (AMPK-mTOR), though combination strategies targeting multiple pathways will likely be required for durable disease reversal. These findings necessitate the expansion of regulatory screening paradigms to incorporate cellular stress pathway biomarkers alongside traditional nuclear receptor endpoints, ensuring comprehensive hepatotoxic risk assessment of emerging BPA substitutes. Full article

Atherosclerosis (AS) is a leading cause of death and disability in type 2 diabetes mellitus (T2DM). However, the shared molecular mechanisms linking T2DM and atherosclerosis have not been fully elucidated. We analyzed AS- and T2DM-related gene expression profiles from the Gene Expression Omnibus (GEO) database to identify overlapping differentially expressed genes and co-expression signatures. Functional enrichment (Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)) and protein–protein interaction (PPI) network analyses were then used to describe the pathways and interaction modules associated with these shared signatures, We next applied the cytoHubba algorithm together with several machine learning methods to prioritize hub genes and evaluate their diagnostic potential and combined CIBERSORT-based immune cell infiltration analysis with single-cell RNA sequencing data to examine cell types and the expression patterns of the shared genes in specific cell populations. We identified 72 shared feature genes. Functional enrichment analysis of these genes revealed significant enrichment of inflammatory- and metabolism-related pathways. Three genes—IL1B, MMP9, and P2RY13—emerged as shared hub genes and yielded robust ANN-based predictive performance across datasets. Immune deconvolution and single-cell analyses consistently indicated inflammatory amplification and an imbalance of macrophage polarization in both conditions. Biology mapped to the hubs suggests IL1B drives inflammatory signaling, MMP9 reflects extracellular-matrix remodeling, and P2RY13 implicates cholesterol transport. Collectively, these findings indicate that T2DM and AS converge on immune and inflammatory processes with macrophage dysregulation as a central axis; IL1B, MMP9, and P2RY13 represent potential biomarkers and therapeutic targets and may influence disease progression by regulating macrophage states, supporting translational application to diagnosis and treatment of T2DM-related atherosclerosis. These findings are preliminary. Further experimental and clinical studies are needed to confirm their validity, given the limitations of the present study. Full article

Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns—often referred to as enterotype-like clusters—correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance for metabolic and gastrointestinal health. This narrative review synthesizes current evidence describing the interplay between microbial composition, BA metabolism, and metabolic dysfunction. A structured literature search was conducted in PubMed, Web of Science, EMBASE, and Scopus using predefined keywords related to bile acids, microbiome composition, metabolic disorders, and enterotypes. Studies were screened for human clinical relevance and mechanistic insights into BA–microbiome interactions. Across the evidence base, Bacteroides-, Prevotella-, and Ruminococcus-associated community types consistently demonstrate different BA transformation capacities that influence secondary BA production and downstream host signaling through FXR and TGR5. These differences are linked to variation in metabolic dysfunction-associated steatotic liver disease, obesity, type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Host genetic variations in BA synthesis, transport, and signaling further modify these microbiome–BA interactions, contributing to the heterogeneity of dietary intervention responses. Overall, the literature supports a model in which microbiome-derived BA profiles act as metabolic phenotypes that shape host lipid and glucose homeostasis, inflammation, and gut–liver axis integrity. Emerging clinical applications include microbiome-stratified dietary strategies, targeted probiotics with defined BA-modifying functions, and therapeutic approaches that align BA-modulating interventions with an individual’s microbial metabolic capacity. Establishing integrated biomarker platforms combining microbiome clustering with BA profiling will be essential for advancing precision nutrition and personalized management of metabolic and gastrointestinal diseases. Full article