Search Results (10,445)

Background/Objective: Neuroimmune and metabolic dysregulation have been increasingly implicated in the cognitive heterogeneity of autism spectrum disorder (ASD). However, it remains unclear whether anti-inflammatory diets engage distinct biological and cognitive pathways in autistic and neurotypical children. This study examined whether a 12-week anti-inflammatory dietary protocol produces group-specific neuroimmune–metabolic signatures and cognitive responses in autistic children, neurotypical children receiving the same diet, and untreated neurotypical controls. Methods: Twenty-two children (11 with ASD, six a on neurotypical diet [NT-diet], and five neurotypical controls [NT-control]) completed pre–post assessments of plasma IFN-γ, CXCL1, RANTES (CCL5), trimethylamine-N-oxide (TMAO), and an extensive ENI-2/WISC-IV neuropsychological battery. Linear mixed-effects models were used to test the Time × Group effects on biomarkers and cognitive domains, adjusting for age, sex, and baseline TMAO. Bayesian estimation quantified individual changes (posterior means, 95% credible intervals, and posterior probabilities). Immune–cognitive coupling was explored using Δ–Δ correlation matrices, network metrics (node strength, degree centrality), exploratory mediation models, and responder (≥0.5 SD domain improvement) versus non-responder analyses. Results: In ASD, the diet induced robust reductions in IFN-γ, RANTES, CXCL1, and TMAO, with decisive Bayesian evidence for IFN-γ and RANTES suppression (posterior P(δ < 0) > 0.99). These shifts were selectively associated with gains in verbal learning, semantic fluency, verbal reasoning, attention, and visuoconstructive abilities, whereas working memory and executive flexibility changes were heterogeneous, revealing executive vulnerability in individuals with smaller TMAO reductions. NT-diet children showed modest but consistent improvements in visuospatial processing, attention, and processing speed, with minimal biomarker changes; NT controls remained biologically and cognitively stable. Network analyses in ASD revealed a dense chemokine-anchored architecture with CXCL1 and RANTES as central hubs linking biomarker reductions to improvements in fluency, memory, attention, and executive flexibility. ΔTMAO predicted changes in executive flexibility only in ASD (explaining >50% of the variance), functioning as a metabolic node of executive susceptibility. Responders displayed larger coordinated decreases in all biomarkers and broader cognitive gains compared to non-responders. Conclusions: A structured anti-inflammatory diet elicits an ASD-specific, coordinated neuroimmune–metabolic response in which suppression of CXCL1 and RANTES and modulation of TMAO are tightly coupled with selective improvements in verbal, attentional, and executive domains. Neurotypical children exhibit modest metabolism-linked cognitive benefits and minimal immune modulation. These findings support a precision-nutrition framework in ASD, emphasizing baseline immunometabolic profiling and network-level biomarkers (CXCL1, RANTES, TMAO) to stratify responders and design combinatorial interventions targeting neuroimmune–metabolic pathways. Full article

Cellular senescence, a hallmark of aging, involves irreversible growth arrest and an enhanced senescence-associated secretory phenotype (SASP). It is often accompanied by mitochondrial dysfunction and altered inter-organelle communication. Using a chronic oxidative stress model in AML12 hepatocytes, we confirmed senescence by canonical assays (e.g., SA β-gal positivity and proliferation arrest) and observed a decline in the RNA-binding protein AUF1 (hnRNP D). AUF1 knockdown further amplified senescent phenotypes, including elongation of mitochondrial network, loss of mitochondrial membrane potential, reduced ATP level, and elevated mitochondrial reactive oxygen species (ROS). In addition, AUF1 knockdown weakened mitochondria-endoplasmic reticulum coupling and reduced mitochondrial Ca²⁺ load. At the molecular level, AUF1 binds to the 3′ untranslated regions (3′UTRs) of Opa1 and Mfn2 and limits their abundance, thereby coupling post-transcriptional control to mitochondrial dynamics. In gain-of-function experiments, ectopic expression of AUF1 attenuated Opa1/Mfn2 induction, restored mitochondrial network architecture, and preserved bioenergetic function under pro-senescent stimuli. Collectively, these findings support a model in which AUF1 preserves mitochondrial homeostasis and thereby restrains the mitochondria–senescence axis in hepatocytes. Full article

Background: Biomedical device-associated infections pose major challenges in surgical care, particularly in hernia repair where polypropylene (PP) meshes and sutures are prone to bacterial colonization and biofilm formation. The limitations of antibiotic resistance and toxicity warrants the need of developing innovative antibacterial strategies. Methods: We developed a composite coating of hydroxypropyl methylcellulose (HPMC) and zinc oxide nanorods (ZnO NP) synthesized via thermal decomposition. This coating was applied to PP meshes and sutures to enhance anti-adhesive properties. The study evaluated surface hydrophilicity through water contact angles, estimation of Zn²⁺ ions using inductively coupled plasma–mass spectrometry (ICP-MS), and long-term efficacy over six months. Safety was assessed via systemic toxicity studies in murine models. Results: The ZnO NPs exhibited potent antibacterial efficacy, achieving up to 99.999% killing against Klebsiella pneumoniae. When applied as an HPMC-ZnO coating, PP meshes and sutures demonstrated enhanced hydrophilicity, reducing water contact angles by ~41° and facilitating prevention of bacterial adhesion. The coated meshes inhibited bacterial attachment by 83% (Escherichia coli), 60% (Pseudomonas aeruginosa), 99.6% (K. pneumoniae), and 99% (Staphylococcus aureus). Similarly, coated sutures reduced adhesion by 67–96% across these strains. Long-term storage studies showed retained antibiofilm efficacy for up to six months. In vivo assessments indicated negligible systemic toxicity of ZnO NPs in murine models. Conclusions: Collectively, these findings highlight HPMC-ZnO NPs coatings as a safe, durable, and effective strategy to functionalize PP-based meshes and sutures, reducing the risk of surgical site infections and demonstrating the potential for broader biomedical applications. Full article

Metabolites, once viewed mainly as energy substrates or structural precursors, are now increasingly recognized as key extracellular signaling mediators that regulate diverse physiological processes. This review synthesizes and systematizes current knowledge on metabolite-mediated signaling through G-protein-coupled receptors (GPCRs) in teleosts and, importantly, highlights new conceptual links between specific metabolite–GPCR axes and key physiological functions relevant to aquaculture. By integrating evidence across metabolite–GPCRs axes, including succinate–SUCNR1, aromatic amino acids (tryptophan and phenylalanine)–GPR142, basic amino acids (L-arginine)–GPRC6A, and lactate–GPR81. We clarify how metabolite–receptor interactions have the potential to modulate glucose homeostasis, immune responses, energy metabolism, and stress coping. A major contribution of this review is illustrating how metabolites act not only as nutrients but also as extracellular signaling molecules governing core physiological processes via GPCRs. Particularly from an evolutionary perspective, compared with peptide-activated GPCRs, metabolite-sensing GPCRs are relatively conserved across different species, suggesting that relevant findings from biomedical research could be translated to aquaculture applications. Therefore, understanding GPCR-mediated metabolite sensing provides a molecular foundation for improving nutrient formulation, developing functional feeds, and designing selective breeding strategies in precision aquaculture. Full article

Lactate, as a pivotal metabolite generated by the body, has attracted considerable attention in numerous biological disciplines in recent years. In addition to its role in supplying energy, lactate also functions as a signaling molecule, with the capacity to mediate a diverse array of physiological effects. Within the central nervous system, lactate is involved in the regulation of critical physiological processes, including neurogenesis, synaptic plasticity, mitochondrial biogenesis, neuroinflammation, and cerebral angiogenesis. Furthermore, lactate has been implicated in the pathogenesis of several central nervous system diseases, such as Alzheimer’s disease, stroke, and spinal cord injury, among others. Physical exercise is recognized as a significant neuroprotective strategy; however, further research is required to elucidate the underlying biological mechanisms. In essence, the role of lactate as a metabolic-epigenetic core is gradually becoming a subject of increasing academic interest. The regulatory function of lactate is thought to involve its production (via lactate dehydrogenase), shuttle (via monocarboxylate transporters), sensing (via G protein-coupled receptor 81), and lactylation modifications, among others. This review synthesizes current evidence to elucidate the multifaceted roles of lactate in central nervous system physiology and pathology under exercise regulation, with a view to bridging the gap between molecular mechanisms and therapeutic potential, thereby paving the way for novel strategies in central nervous system disease intervention. Full article

Functional steel surfaces engineered through tailored micro-nano structures are increasingly vital for various applications such as high-performance aerospace components, energy conversion systems and defense equipment. Femtosecond laser filament processing is a recently proposed remote fabrication technique, showing the capability of fabricating micro-nano structures on irregular and large-area surfaces without the need of tight focusing. Nevertheless, the mechanisms underlying the formation of filament-induced structures remain not fully understood. Here we systematically investigate the formation mechanisms of filament-induced micro-nano structures on stainless steel surfaces by processing stainless steel in three manners: point, line, and area. We clarify the decisive role of the unique core–reservoir energy distribution of the filament in the formation of filament-induced micro-nano structures, and reveal that ablation, molten metal flow, and metal vapor condensation jointly drive the structure evolution through a dynamic interplay of competition and coupling, giving rise to the sequential morphological transitions of surface structures, from laser-induced periodic surface structures to ripple-like, crater-like, honeycomb-like, and ultimately taro-leaf-like structures. Our work not only clarifies the mechanisms of femtosecond laser filament processed morphological structures on steels but also provides insights onto intelligent manufacturing and design of advanced functional steel materials. Full article

Climate change and human activities have intensified the imbalance between water supply and demand in the Shule River Basin. Prominent issues such as groundwater over-exploitation and insufficient ecological base flow have significantly constrained the high-quality development of the region. An evaluation system was developed comprising 20 indicators across four subsystems: water resources, society, economy, and ecosystems. The entropy weighting method was employed to determine the weights of each indicator. The coupling coordination degree of the water resource–society–economy–ecosystem system from 2003 to 2022 was assessed using a coupling coordination degree model. Network analysis was applied to evaluate the correlation and connectivity among indicators. A barrier diagnostic model based on indicator deviation was further constructed to identify key constraints within the system. The results showed that the overall coordination degree of the coupled system increased from 0.217 in 2003 to 0.409 in 2022, shifting from a moderately uncoordinated state to a weakly coordinated one. However, the coordination level remained low due to fluctuations in the water resource subsystem. The ecological and economic subsystems functioned as critical coupling hubs, while strong negative interactions within the water resource subsystem emerged as major constraints to coordinated development. Long-term dominant barriers included the proportion of water used for ecological and agricultural purposes, as well as per capita food production. After 2019, water resource-related indicators, such as per capita water availability and water production modulus, showed a marked increase in obstruction levels, highlighting the persistent challenges posed by water scarcity and inefficient utilization. Full article

Linear cultural heritage is characterized by complex cross-regional and multi-level features, facing severe challenges of spatial resource fragmentation and an imbalance in cultural and tourism functions. However, existing research lacks quantitative analysis regarding the non-linear driving mechanisms of spatial distribution and the misalignment of culture–tourism coupling. In this study, we construct an integrated identification–explanation–coupling–governance (IECG) theoretical framework. Taking The Great Tea Road (Jinzhong Section) as a case study, our framework integrates the CCSPM, XGBoost-SHAP machine learning interpreter, and Geodetector to systematically quantify the spatial structure of heritage and the level of culture–tourism integration. The results indicate that, (1) in terms of spatial patterns, the study area exhibits an unbalanced agglomeration characteristic of “dual-primary and dual-secondary cores,” with high-density areas showing significant orientation along rivers and roads; (2) regarding driving mechanisms, the machine learning model reveals a significant “non-linear threshold effect,” with 83% of driving factors (e.g., elevation and distance to transportation) exhibiting non-linear fluctuations in their influence on heritage distribution; and, (3) in terms of culture–tourism coupling, the overall coupling coordination degree (CCD) is low (mean 0.38), indicating significant “resource–facility” spatial misalignment. The modern number of public cultural facilities (NCF) is identified as the primary obstacle restricting the transformation of high-grade heritage into tourism products. Based on these findings, we propose adaptive zoning governance strategies. This research not only theoretically clarifies the complexity of the social–ecological system of linear heritage but also provides a generalizable quantitative method for the digital protection and sustainable tourism planning of cross-regional cultural heritage. Full article

Abductive reasoning, or abduction, is a key process in scientific discovery and medical diagnosis. In everyday dermatology and dermatopathology, however, it functions as the practical engine behind differential diagnosis, clinicopathologic correlation, and disciplined pattern recognition. In this paper, we retain the epistemological foundation of abduction but translate it into usable steps for clinicians and dermatopathologists. We distinguish abduction from deduction and induction; separate creative abduction (which generates new concepts) from selective abduction (daily diagnostic choice); and show how both operate within a simple Select-and-Test (ST) Model: select a hypothesis, deduce what else should be true, test against data, and then update. We then reinterpret Ackerman’s algorithmic method of pattern analysis as an operationalization of the ST-Model. Through a couple of concise case vignettes, we illustrate visual and manipulative abduction, nonmonotonic updates, and the role of artifacts (dermoscopy, DIF, stains) as so-called epistemic mediators. Finally, we map contemporary AI tools to selective abduction and propose practical guardrails for fairness, transparency, and accountability. The result is a pragmatic framework that preserves philosophical depth while addressing the daily needs of dermatologists and dermatopathologists in the clinic and at the microscope. Full article

Microwave, millimeter-wave, and terahertz devices are fundamental to modern 5G/6G communications, automotive imaging radar, and sensing systems. As essential RF front-end elements, passive microwave array components on static platforms remain constrained by fixed geometry and single-frequency excitation, leading to limited spatial resolution and weak interference suppression. Phase-steered arrays offer angular control but lack range-dependent response, preventing true two-dimensional focusing. Frequency-Diverse Array Multiple-Input Multiple-Output (FDA-MIMO) architectures introduce element-wise frequency offsets to enrich spatial–spectral degrees of freedom, yet conventional linear or predetermined nonlinear offsets cause range–angle coupling, periodic lobes, and restricted beamforming flexibility. Existing optimization strategies also tend to target single objectives and insufficiently address target- or scene-induced perturbations. This work proposes a nonlinear frequency-offset design for passive microwave arrays using a Dingo–Gray Wolf hybrid intelligent optimizer. A multi-metric fitness function simultaneously enforces sidelobe suppression, null shaping, and frequency-offset smoothness. Simulations in static scenarios show that the method achieves high-resolution two-dimensional focusing, enhanced interference suppression, and stable performance under realistic spatial–spectral mismatches. The results demonstrate an effective approach for improving the controllability and robustness of passive microwave array components on static platforms. Full article

Background/Objectives: The circadian regulator, circadian locomotor output cycles kaput (CLOCK), is well-established in maintaining sleep–wake rhythms, yet its cell-type-specific functions in sleep regulation remain largely unexplored. While ventromedial hypothalamic (VMH) prodynorphin (PDYN)-expressing (VMH^PDYN+) neurons are known to modulate homeostatic and motivational processes, their potential role in circadian sleep regulation has not been investigated. Methods: To address this, we developed mice with PDYN neuron-specific functional suppression of CLOCK activity (mClkΔ19) by interfering with their internal clock through Adeno-Associated Virus (AAV)-mediated overexpression of dominant-negative CLOCKΔ19 in PDYN-Cre mice. Results: We found that mClkΔ19 mice exhibited reduced locomotor activity during the dark phase, earlier activity peaks, and impaired rhythmicity of rapid eye movement (REM) and non-REM (NREM) sleep. Sleep analysis in mClkΔ19 mice showed selective reductions and fragmentation of light-phase REM sleep, more frequent sleep–wake transitions, and shorter REM cycles during the dark phase, indicating disrupted REM sleep timing. EEG spectral analysis in mClkΔ19 mice revealed decreased gamma activity during REM sleep in the light phase and an increase in delta activity coupled with decreased gamma during wakefulness in the dark phase. Conclusions: These findings suggest that the CLOCK activity in VMH^PDYN+ neurons is vital for circadian accuracy, REM sleep stability, and brain oscillations during sleep–wake cycles. Full article

Severe lost circulation frequently occurs in deep and ultra-deep wells under high-temperature/high-pressure (HPHT) conditions and in fracture-cavity composite loss channels. Conventional lost-circulation materials (LCMs) often fail because of premature loss of mobility, insufficient residence in loss paths, and irreversible failure after solidification. Cement-based sealing systems, owing to their ability to plug large leakage channels and their cost-effectiveness, have become the mainstream solution. To improve their performance under extreme downhole conditions, recent studies have focused on base-cement design, reinforcement phases, and property regulation strategies-including the use of granular/fibrous/nanoscale additives for bridging reinforcement, rheology and thickening control to enhance injectability and residence, and chemical/functional modifiers to improve compactness and durability of the hardened matrix. Significant progress has been achieved in terms of HPHT resistance, densification design, regulation of rheological properties and thickening behavior, and self-healing/responsive sealing functions. However, most existing studies still focus on improving individual properties and lack a cross-scale, holistic design and unified mechanistic perspective for fracture-cavity coupled flow and long-term sealing stability. Distinct from previous reviews that mainly catalogue material types or discuss single-performance optimization, this review is framed by fracture-cavity composite loss channels and long-term sealing requirements under HPHT conditions, systematically synthesizes the material design strategies, reinforcement mechanisms and applicability boundaries of cement-based plugging systems, builds cross-scale linkages among these aspects, and proposes future research directions toward sustainable plugging design. Full article

Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein conformation, which can be precisely regulated through processing and fabrication strategies. Recent advances in bioengineering have further expanded the capabilities of BMSF, enabling the development of biomaterials with engineered architectures, tailored microtopographies, and enhanced bioactivity. These technological developments have facilitated the design of scaffolds that more effectively guide tissue regeneration and enhance functional outcomes. Such constructs have demonstrated promising outcomes in the regeneration of bone, cartilage, vascular, neural, corneal, and skin tissues. This review summarises current progress while emphasising emerging trends that couple BMSF’s unique molecular features with immune-responsive design, instructive microarchitectures that guide cell behaviour, composite scaffold design, and functionalisation with bioactive molecules. BMSF has been positioned as a structurally adaptable and biologically instructive platform whose continued progression will depend on integrating advanced fabrication, mechanistic understanding, and translational standardisation. Full article

Background/Objectives: Neuroblastoma (NB) is the most common extracranial solid tumor in children and accounts for 12–15% of pediatric cancer-related deaths. Current multimodal therapies lack specific cellular targets, causing systemic toxicity and drug resistance. The development of innovative tumor-targeted nanoformulations might represent a promising approach to enhance NB diagnosis and antitumor efficacy, while decreasing off targets side effects. Fibronectin extra-domain B (FN-EDB) is upregulated in the tumor microenvironment. Methods: FN-EDB expression was evaluated by immunohistochemical staining in cell line-derived and tumor patient-derived animal models of NB. A gold nanoparticle, decorated with an antibody (Ab) recognizing FN-EDB (L19-AuNP) was developed by the company Nano Flow and its tumor binding was tested by ELISA in vitro and in patient-derived xenograft (PDX) models of NB by photoacoustic imaging in vivo. Results: All animal models of NB used have been shown to express FN-EDB. L19 Ab demonstrated excellent binding specificity to FN-EDB both when used in free form and after conjugation to AuNP. Compared to the non-functionalized (no Ab L19-coupled) AuNP, which showed an increase in PDI and zeta potential over time, making them unsuitable for use in in vivo studies, L19-AuNP demonstrated good stability. In vivo, L19-AuNP specifically homed into PDX models of NB, accumulating better in tumors expressing higher levels of FN-EDB. Negligible distribution to healthy organs occurred. Conclusions: In this preliminary study, L19-AuNP was shown to be a novel diagnostic tool specifically for binding NB expressing FN-EDB, paving the way for the development of theranostic nanoformulations co-encapsulating gold moiety and standard-of-care therapy for NB. Full article

Major depressive disorder (MDD) is increasingly recognized as a disorder of impaired neuroplasticity and large-scale network dysfunction rather than a simple monoaminergic deficit. Converging evidence indicates that chronic stress and depression erode synaptic connectivity, reduce glial support, and destabilize functional interactions among the default mode, salience, and executive networks. Conventional antidepressants indirectly restore circuit function over weeks, but the advent of rapid-acting glutamatergic agents has opened a new path for targeting these abnormalities directly. In this narrative review, we synthesize molecular, cellular, and connectomic findings to outline a conceptual Connectomic Glutamate Framework of Depression. We first examine how NMDAR blockade and subsequent AMPAR facilitation activate mTORC1 and BDNF signaling, driving synaptogenesis and dendritic spine formation. We then highlight the role of astrocytes and microglia in shaping the “quad-partite synapse” and sustaining network integrity. Neuroimaging studies demonstrate that glutamatergic modulators remodel dysfunctional networks: dampening DMN hyperconnectivity, enhancing fronto-limbic coupling, and normalizing salience-driven switching. Integrating these domains, we propose a hypothesis-generating, two-phase model in which glutamatergic agents destabilize maladaptive attractor states and then reintegrate circuits through structural remodeling. This framework bridges molecules, cells, and networks, offering mechanistic insight into the rapid efficacy of glutamatergic antidepressants and highlighting priorities for clinical translation. Full article