Search Results (2,428)

Background: Adipose tissue is increasingly recognized as a highly dynamic endocrine and immunometabolic organ with marked functional heterogeneity. It serves as a reservoir for the active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ or calcitriol (1α,25-D₃), since it expresses enzymes responsible for its activation and inactivation and contains the vitamin D receptor (VDR). Through both classical and non-classical mechanisms, calcitriol modulates adipocyte proliferation and differentiation, protein expression and energy metabolism. This review aims to explore the signal transduction mechanisms of calcitriol in adipocytes, detailing the classical pathways mediated by the nuclear VDR (VDRn), as well as non-classical pathways involving membrane-associated VDR (VDRm), microRNAs, AMP-activated protein kinase (AMPK), and sirtuin 1 (SIRT1). Methods: A literature search was conducted using PubMed, ScienceDirect, and MDPI-indexed journals, prioritizing studies published within the last 10 years to ensure the inclusion of up-to-date evidence. Results: This review summarizes current knowledge on both classical and non-classical signaling pathways that are activated by calcitriol and highlights key molecular targets with potential relevance for drug development and therapeutic intervention. Through VDRn, calcitriol regulates the expression of proteins involved in inflammation and energy metabolism. Additionally, it modulates cellular processes such as energy production and secretion via the AMPK/SIRT1 axis and microRNA-mediated pathways, contributing to mitochondrial function and metabolic homeostasis. Conclusions: Calcitriol plays a central role in adipocyte biology by integrating multiple signaling pathways that regulate metabolic and inflammatory responses. These mechanisms highlight its potential as a therapeutic target and biomarker in metabolic diseases. Moreover, microRNAs emerge as critical posttranscriptional regulators in these processes, reinforcing their relevance as both biomarkers and targets for future interventions. Full article

This study examines the role of artificial intelligence (AI) in marine insurance within the Moroccan maritime sector. Drawing on Dynamic Capabilities Theory, the study investigates the relationships among AI Adoption, Risk Assessment Accuracy, Fraud Detection Capability, Claim Processing Efficiency, and Customer Trust, while also examining the mediating role of these operational capabilities. A quantitative survey was conducted among maritime and insurance professionals operating within the Tangier Med and Casablanca port ecosystems, and the data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The findings indicate that AI Adoption is positively associated with Risk Assessment Accuracy, Fraud Detection Capability, and Claim Processing Efficiency. These operational capabilities are also positively associated with Customer Trust and function as significant mediating pathways between AI Adoption and stakeholder confidence. The study contributes to the emerging literature on AI applications in marine insurance by providing empirical evidence from an emerging maritime economy and offers theoretical and practical implications for insurers, maritime operators, and policymakers. Full article

Grapevine downy mildew, caused by the oomycete pathogen Plasmopara viticola (P. viticola), is one of the most devastating diseases threatening the global grape industry. The pathogen invades host plants through stomata, triggering a series of highly coordinated physiological disorders and biochemical defense events. This review systematically summarizes the dynamic changes in morphological structures (stomatal characteristics), physiological functions (photosynthesis, membrane system integrity, and carbon metabolism), and multi-level biochemical defense systems (reactive oxygen species (ROS) scavenging enzyme system, phenylpropanoid metabolic pathway, pathogenesis-related proteins, and phenolic compounds) in grapevines following infection. It focuses on analyzing the differences in the timing, intensity, and metabolic reprogramming of defense responses between resistant and susceptible cultivars, pointing out that the essence of disease resistance lies in early pathogen recognition and rapid defense induction. The conflicting conclusions regarding indicators such as soluble sugars, peroxidase (POD), and superoxide dismutase (SOD) are discussed from the perspectives of experimental systems, cultivar genetic backgrounds, and pathogen physiological race differences. Furthermore, the known physiological and biochemical alterations are linked to upstream signaling pathways, including salicylic acid and jasmonic acid (SA/JA), calcium signaling, and mitogen-activated protein kinase (MAPK) cascades. Recent advances in revealing resistance mechanisms in the omics era are also introduced. Finally, future research directions are proposed, including constructing multi-indicator dynamic evaluation models, verifying key gene functions using gene editing, exploring the potential of epigenetic regulation, and developing integrated control strategies combined with microbiome research. This review aims to provide theoretical support for grapevine downy mildew resistance breeding and sustainable disease management. Full article

α-Synuclein (α-Syn) is a key presynaptic protein, primarily known for its role in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, including dementia with Lewy bodies (DLB). Although much of the research has focused on the nigrostriatal dopamine (DA) pathway, there is growing recognition that the accumulation of misfolded α-Syn in the prefrontal cortex (PFC) is a critical driver of non-motor symptoms and cognitive deficits in PD and DLB. This review examines the dual role of α-Syn in the PFC circuitry, initially exploring its regulation of synaptic vesicle (SV) dynamics and recycling to maintain stable neurotransmission. We highlight its contribution to the modulation of glutamatergic (Glu) and GABAergic (γ-aminobutyric acid, GABA) synapses, which ensures the functional excitatory/inhibitory (E/I) balance of prefrontal circuits. Conversely, in PD and DLB, the transition of functional α-Syn monomers to pathological oligomers triggers a cascade of synaptic failures. We analyze how α-Syn aggregation causes pathology in dendritic spines, leads to a progressive reduction in the density of synaptic markers, and impairs cortical plasticity. Synthesizing evidence from neuroimaging studies, post-mortem human cortical samples, and animal models, this review emphasizes the PFC as a vulnerable brain region where α-Syn-mediated synaptic dysfunction translates into cognitive and emotional deficits. Deciphering these early synaptic alterations is essential for developing neuroprotective strategies that preserve cortical function in PD and DLB. Full article

Plants must continuously balance the trade-offs between growth and defense, a constraint that is exacerbated by biotic and abiotic stresses, particularly when they occur together. Ethylene (ET) serves as a central, integrative regulatory node controlling this by linking developmental programs to stress-responsive signaling networks. Advances at the molecular and systems levels have revealed that ET mediates the redistribution of metabolic resources via coordinated regulation of its synthesis, perception, and downstream signaling. The ETR (Ethylene Receptor)-CTR1 (Constitutive Triple Response 1)-EIN2 (Ethylene Insensitive 2)-EIN3(Ethylene Insensitive 3) signaling module lies at the core of this network, integrating multiple hormonal pathways. Through dynamic crosstalk with jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), auxin (AUX), and gibberellins (GA), ET enables the fine-tuned coordination of growth inhibition, immune activation, and stress acclimation in response to environmental fluctuations. Processes such as induced systemic resistance, programmed cell death, and architectural plasticity further reinforce this regulatory framework, with ethylene-responsive transcription factors, including ERFs (ethylene responsive factor gene family) and WRKYs, acting as critical convergence points. Emerging insights into ACC (1-aminocyclopropane-1-carboxylic acid) -dependent signaling, chromatin remodeling, and tissue-specific regulation expand the functional scope of ET beyond traditional hormone paradigms. At the same time, the ability of pathogens to manipulate ET signaling underscores its dual role in both promoting immunity and facilitating susceptibility. By integrating molecular, physiological, and ecological perspectives, this review highlights ET as a central coordinator of plant stress resilience and growth optimization, providing a unifying framework for understanding how plants adapt to complex and dynamic environments. Full article

Aqueous zinc–manganese dioxide (Zn–MnO₂) batteries are undergoing a paradigm shift from traditional ion-insertion mechanisms to a reversible deposition/dissolution process. By leveraging a two-electron transfer (Mn²⁺/MnO₂), this electrolytic system achieves a high theoretical capacity of 616 mAh g⁻¹ and a theoretical operating voltage of 1.99 V. However, the accumulation of dead Mn, electrically isolated inactive phases, and dynamic interfacial pH fluctuations remain critical barriers to cycle life and practical energy density. This review systematizes a trinitarian strategy to overcome these bottlenecks, focusing on interfacial engineering, redox mediator-assisted recovery, and advanced electrode architectures. We evaluate how anion engineering and pH-buffering stabilize reaction pathways, and how diverse mediators (e.g., halogens, metal ions, and organic molecules) chemically rescue inactive manganese. Furthermore, we examine the integration of 3D carbon networks and low-cost hybrid electrodes to sustain high-areal-capacity deposition. To elucidate these complex mechanisms, we highlight multiscale analytical approaches combining synchrotron X-ray techniques and density functional theory (DFT). Finally, we outline a roadmap for applications ranging from grid-scale flow batteries to flexible wearable electronics. This work provides a comprehensive perspective on realizing sustainable, safe, and high-performance zinc-based energy storage. Full article

Autism spectrum disorder is increasingly linked to altered microglial biology. However, current research models are limited by outdated descriptions of microglial “activation”. Here, we propose that microglial involvement in ASD is best understood as a problem of state mismatch, in which temporally programmed and regionally specialized microglial states fail to align with local developmental demands. We synthesize evidence across genetic models, human transcriptomics, and experimental systems to examine three axes of misalignment: developmental timing, circuit specificity, and functional phenotype. These mismatches produce divergent outcomes, including both excessive and insufficient synaptic pruning, and reflect a decoupling between microglial activation markers and effector capacity. We further evaluate molecular recognition systems governing microglia–synapse interactions, with emphasis on complement signaling and glycan-mediated pathways such as sialic acid–Siglec signaling and polysialylation. While glycosylation is not a universal driver of ASD pathology, it represents a plausible regulatory layer controlling synapse visibility and microglial engagement. This framework reconciles conflicting findings in the literature and positions microglia as dynamic developmental effectors whose misaligned state trajectories contribute to circuit-level dysfunction in ASD. Full article

Cancer stem cells (CSCs) constitute a resilient tumor subpopulation responsible for multidrug resistance, metastasis, and clinical relapse. A cardinal hallmark of these cells is profound metabolic plasticity. This dynamic defense mechanism facilitates rapid shifts between glycolysis, oxidative phosphorylation (OXPHOS), and alternative nutrient catabolism, enabling CSCs to bypass microenvironmental constraints. This review delineates how glycolytic adaptation functions as a primary driver of therapy resistance within the CSC niche. We dissect the regulatory triad controlling these metabolic shifts, which includes rate-limiting enzymes, epigenetic and epitranscriptomic remodeling, and master transcription factors. Glycolytic reprogramming transcends bioenergetics by acting as a metabolic signaling node. It integrates with the epithelial–mesenchymal transition (EMT) program, autophagic pathways, and the immunosuppressive tumor microenvironment (TME) to fortify CSC survival. We appraise emerging therapeutic interventions targeting these metabolic vulnerabilities. Strategies focus on optimizing small-molecule inhibitors, nanotechnology-enabled delivery systems, and immunometabolic combination regimens. This review establishes a conceptual framework for precision interventions aimed at disrupting CSC plasticity, overcoming therapeutic resistance, and preventing tumor recurrence. Full article

Alternative splicing (AS) is a major post-transcriptional regulatory mechanism that greatly expands transcriptomic and proteomic diversity in plants. Recent studies have demonstrated that AS dynamically regulates gene expression during plant development and under diverse environmental conditions through isoform-specific modulation of transcript stability, translation efficiency, protein localization, and signaling pathways. In this review, we summarize recent advances in understanding the roles of AS in plant development and abiotic stress responses. Mechanistically, splice site selection is regulated through coordinated interactions among cis-regulatory elements, RNA-binding proteins, RNA secondary structures, transcriptional kinetics, chromatin organization, and spliceosomal dynamics. AS plays critical roles in various developmental processes, including seed germination, vegetative growth, flowering transition, and senescence, while also contributing to plant adaptation to abiotic stresses such as osmotic, temperature, and oxidative stresses. Particular emphasis is placed on the diverse regulatory outcomes of AS, including isoform-specific protein functions, AS-coupled nonsense-mediated decay, transcript stability control, and context-dependent isoform switching. We further discuss the varying levels of experimental evidence supporting reported AS events, ranging from transcriptome-wide observations to genetically and biochemically validated isoform functions. Moreover, recent advances in long-read sequencing, single-cell transcriptomics, proteogenomics, and genome-engineering technologies are accelerating the functional characterization of splice isoforms and uncovering the complexity of AS-mediated regulatory networks. Collectively, these advances highlight AS as a central mechanism coordinating plant developmental plasticity and environmental adaptation. Full article

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and reversible depletion of targeted macrophage populations, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablation. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Secreted Phosphoprotein 1 (Spp1) (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which Cx3cl1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation. Full article

The integration of the digital and real economies is a pivotal engine driving the development of new, quality productive forces. Tourism ecological governance is the concrete manifestation of the green dimension of new-quality productive forces in the cultural and tourism sector, as well as being a path for converting ecological value to drive regional sustainable development. The relationship and mechanisms between digital–real integration and tourism ecological governance are critical issues requiring urgent breakthroughs. However, existing research primarily explores the economic factors influencing tourism ecology and has yet to systematically reveal the intrinsic mechanisms through which digital–real integration affects tourism ecological efficiency from the perspective of typical ecological functional zones. Based on data from 78 counties (municipalities, districts) in China’s Taihang Mountains from 2011 to 2023, this study examines the impact of digital–real integration on tourism ecological efficiency and its operational pathways. The findings are as follows: Firstly, from a temporal evolution perspective, tourism ecological efficiency in the Taihang Mountains underwent a phase of dynamic adjustment and gradual improvement between 2011 and 2023, while the level of digital–real integration experienced a phase of general enhancement and phased advancement. From a spatial evolution perspective, neighboring sub-regions within the Taihang Mountains exhibit positive spatial correlations in terms of both digital–real integration and tourism ecological efficiency. From the perspective of spatiotemporal transfer characteristics, changes in tourism ecological efficiency and the level of integration of the digital and real economies in the Taihang Mountains are influenced by neighboring regions. The development processes of tourism ecology and digital–real integration exhibit a relatively stable and gradually improving pattern, driving the agglomeration of regions toward higher levels. Secondly, digital–real integration has a positive impact on improving tourism ecological efficiency by releasing ecological pressure, promoting industrial synergy agglomeration, and driving green innovation development. Heterogeneity analysis reveals that the positive effect of this integration on tourism ecological efficiency is more pronounced in national e-commerce demonstration cities. Digital–real integration has had a positive impact on improving tourism ecological efficiency in the Southern and Western Taihang Mountain regions, while its impact on the Eastern Taihang Mountain region was not statistically significant. This study incorporates digital–real integration with tourism ecological efficiency, as well as environmental, structural, and capacity factors, into a unified analytical framework, providing theoretical references and practical insights for exploring pathways of digital transformation and innovative tourism ecological governance in ecologically sensitive functional zones. Full article

Lateral femoral neck and peritrochanteric fractures are common and clinically challenging injuries, particularly in the elderly population, with significant implications for morbidity, mortality, and functional recovery. Traditional classification systems are widely used to guide treatment, yet their reproducibility and clinical applicability remain debated. Increasing attention has been directed toward trabecular architecture and its role in fracture behavior and reduction strategies. This review aims to summarize current evidence on classification systems, trabecular-based fracture patterns, pre-operative reduction techniques, and fixation strategies. A narrative review was conducted using PubMed/MEDLINE, Embase, and Scopus databases up to May 2026. Original studies, reviews, and biomechanical investigations focusing on proximal femur fracture classification, reliability, trabecular alignment, reduction techniques, and fixation methods were included. Data were qualitatively analyzed, with emphasis on interobserver reliability, biomechanical implications, and clinical outcomes. Conventional classification systems, including anatomical, Evans–Jensen, and AO/OTA frameworks, demonstrated variable and generally moderate reproducibility, with reported interobserver agreement ranging from approximately κ = 0.30 to 0.60. Emerging evidence highlights the importance of trabecular architecture, distinguishing intradigital fractures—confined within trabecular pathways and relatively stable—from extradigital fractures, which disrupt load-bearing structures and are associated with increased mechanical instability and higher failure rates. Biomechanical and clinical studies indicate that inadequate reduction with trabecular misalignment significantly increases the risk of varus collapse and implant cut-out. Reduction strategies tailored to fracture pattern, such as internal rotation for intradigital fractures and external or combined maneuvers for extradigital patterns, improve alignment and load transfer. In terms of fixation, dynamic hip screws remain effective in stable fractures, whereas cephalomedullary nails demonstrate superior performance in unstable patterns, with lower reoperation rates reported (approximately 5–8% vs. 10–15%). Management of lateral femoral neck and peritrochanteric fractures should extend beyond traditional classification systems to incorporate trabecular biomechanics. Restoration of trabecular alignment, alongside established parameters such as neck–shaft angle and tip–apex distance, is critical for optimizing outcomes. Further prospective studies are needed to validate trabecular-based classifications and standardize reduction strategies. Full article

Peroxisomes are essential metabolic organelles that support core aspects of cellular homeostasis. In the hepatocytes, peroxisomes govern key aspects of cellular homeostasis, including processing lipid substrates that are inadequately handled by mitochondria, controlling hydrogen peroxide metabolism, and regulating bile acid synthesis. Increasing evidence indicates that these organelles are not merely auxiliary metabolic compartments but active contributors to the development and progression of liver disease. Dynamic alterations in peroxisomal proteins and function are being noted. Across metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic disorders, fibrosis, and hepatocellular carcinoma, peroxisomes undergo remodeling that shows a change from adaptive reactions to maladaptive states. These changes perturb signaling pathways that regulate inflammation, stress responses, and cell fate. In addition, because peroxisomes operate within an interconnected organelle network, their dysfunction propagates to mitochondria, endoplasmic reticulum, and other cellular systems, amplifying metabolic and cellular stress. This review summarizes current understanding of how peroxisomal pathways contribute to liver disease, highlighting mechanisms involving lipid accumulation, oxidative stress, and disrupted organelle crosstalk. How peroxisome-dependent control of circulating metabolites links hepatic injury to extrahepatic organ systems is further discussed. At the end, emerging therapeutic strategies for liver disease targeting peroxisomal pathways are discussed. Together, the emerging understanding of peroxisomal remodeling, metabolic regulation, organelle crosstalk, and inter-organ communication positions peroxisomes as active and dynamic regulators of liver disease and potential targets for therapeutic intervention. Full article

In characterizing unconventional reservoirs, conventional Digital Rock Physics (DRP) has long been constrained by three fundamental bottlenecks: the trade-off between imaging resolution and field of view, challenges in reconstructing multiscale pore topology, and the prohibitive computational cost of direct numerical simulation (DNS) at the pore scale. The deep integration of artificial intelligence and rock physics has given rise to a new paradigm—Intelligent Digital Rock Physics (IDRP). This paper provides a systematic review of the evolutionary trajectory of IDRP, with a focus on how machine learning is reshaping the end-to-end workflow from imaging and segmentation to reconstruction and simulation. First, we survey image super-resolution and 3D pore structure generation techniques based on convolutional neural networks (CNNs), generative adversarial networks (GANs), and diffusion models, elucidating their mechanisms for surpassing optical diffraction limits and incorporating macroscopic petrophysical constraints. Second, we outline algorithmic strategies for fusing multi-source heterogeneous data (e.g., Micro-CT and SEM) and representing dual-porosity or multi-continuum systems. Third, we critically examine the application of machine learning surrogates in single- and multiphase flow prediction, highlighting how physics-informed machine learning (PIML) and reinforcement learning (RL)—by embedding governing equations such as Navier–Stokes or Muskat–Leverett into loss functions—achieve both computational acceleration and physical consistency. We further identify key limitations of current IDRP approaches, including insufficient validation of generated topological realism, narrow generalization across lithologies, inadequate representation of dynamic wettability, and limited model interpretability. Finally, we propose a forward-looking roadmap centered on multimodal foundation models for rocks, coupled with neural operators and uncertainty quantification frameworks, emphasizing the critical pathways for translating IDRP into engineering digital twins for unconventional hydrocarbon development, coalbed methane production enhancement, Enhanced Geothermal Systems, and geological CO₂ storage. This review offers a comprehensive reference for researchers at the intersection of geophysics, rock mechanics, and artificial intelligence. Full article

Anaerobic co-digestion (AcoD) is increasingly applied in sewage-sludge management and organic-waste treatment because it can improve methane recovery, stabilize mixed substrates, and reduce life-cycle greenhouse-gas emissions under appropriate feedstock and operating conditions. However, existing reviews still focus mainly on feedstock types or isolated enhancement measures and less often connect synergistic mechanisms with engineering implementation and carbon outcomes. The specific novelty of this review is to connect functional feedstock classification, mechanism boundaries, engineering controls, and carbon-performance evaluation within one sludge-centered AcoD framework. This review synthesizes recent progress in AcoD of sewage sludge, food waste, livestock manure, crop residues, and industrial organic streams through a chain from feedstock traits to substrate interactions, microbial responses, engineering performance, and carbon benefits. Feedstocks are reorganized by function rather than by waste name, highlighting how carbon-to-nitrogen contrast, buffering capacity, hydrolysis recalcitrance, and inhibitor profiles jointly define synergy potential. Key mechanisms, including C/N balancing, hydrolysis complementarity, inhibitor mitigation, and direct interspecies electron transfer (DIET), are discussed together with their applicability limits. Representative evidence shows methane-yield or methane-production increases of about 41–55% for selected food-waste–manure blends, approximately 45% for rice–straw–pig manure systems after cellulolytic pretreatment, and approximately 16–55% for selected additive strategies; these values are illustrative rather than directly comparable because the underlying studies differ in substrates, baselines, reactor configurations, pretreatment conditions, and operating parameters. The review then translates mechanism into practice through pretreatment, reactor-selection templates, operating windows, additive reinforcement, and artificial-intelligence-assisted monitoring. Representative cases and life-cycle evidence indicate that AcoD can improve methane productivity while lowering greenhouse-gas emissions relative to landfill or mono-digestion pathways when energy substitution and nutrient recycling are credibly counted. Remaining bottlenecks include incomplete kinetic integration, limited DIET quantification, insufficient reporting of quantitative operating ranges and additive dosages, and weak coupling of carbon, economics, and regional feedstock dynamics. The revised review therefore treats AcoD as a sludge-centered mechanism-to-engineering framework and highlights two transferability gaps that require stronger standardization: biodegradation/toxicity testing and local co-substrate logistics. Full article