Search Results (680)

Potato (Solanum tuberosum) is one of the world’s most important food crops, with tuber sink strength and starch deposition determining yield, quality, and processing performance. While starch is the dominant carbohydrate reserve, its accumulation is tightly linked with protein metabolism. Patatin, the major soluble storage protein, constitutes up to 40% of total tuber protein. In addition to serving as a nitrogen and carbon reserve, patatin exhibits lipid acyl hydrolase (phospholipase A₂-like) activity, suggesting roles in membrane remodeling and stress signaling. This dual identity places patatin at the intersection of storage, metabolic regulation, and defense. A structured review of studies published between 1980 and 2025 was developed using PubMed, Web of Science, Frontiers, and MDPI databases. Prioritized research included molecular, physiological, and multi-omics analyses of patatin expression, regulation, and function under optimal and stress conditions. Evidence indicates that patatin contributes to carbon–nitrogen balance and sink strength by affecting sucrose import, vacuolar osmotic capacity, and starch biosynthesis. Under drought, salinity, and pathogen stress, patatin transcript levels, protein stability, and enzymatic activity shift, leading to reduced starch deposition, altered sugar accumulation, osmoprotection, and reallocation toward defense responses. Despite these insights, major knowledge gaps remain. These include isoform-specific roles, integration into sugar–hormone regulatory networks, and field-scale responses under fluctuating environments. Future progress will require integrated multi-omics, fluxomics, and proximity-labeling approaches, combined with CRISPR-based isoform editing and promoter engineering. Targeting patatin as both a biomarker and an engineering node offers opportunities to develop climate-ready potato cultivars with improved starch yield, tuber quality, and stress resilience. Full article

Soil-borne pathogens cause devastating root rot diseases in forest ecosystems, often by inducing dysbiosis in the rhizosphere microbiome. While antagonistic bacteria can suppress disease, their effects frequently extend beyond direct inhibition to include ecological restructuring of resident microbial communities. However, the causal relationships between such microbiome restructuring and disease suppression in tree species remain poorly understood. Here, we show that the antagonistic bacterium B. mojavensis dxk33 effectively suppresses F. solani-induced root rot in C. lanceolata, and that this disease suppression coincides with a partial reversal of pathogen-associated dysbiosis in the rhizosphere. Inoculation with dxk33 significantly promoted plant growth and reduced the disease index by 72.19%, while concurrently enhancing soil nutrient availability and key C-, N- and P-cycling enzyme activities. High-throughput sequencing revealed that dxk33 inoculation substantially reshaped the rhizosphere microbiome, counteracting the pathogen’s negative impact on microbial diversity and coinciding with a shift toward a more stable community structure. Under pathogen stress, dxk33 enriched beneficial bacterial taxa such as Pseudomonas and Sphingomonas and suppressed pathogenic fungi while promoting beneficial fungi such as Mortierella. Linear discriminant analysis and functional prediction further indicated that dxk33 remodeled ecological guilds enriched for mycorrhizal and saprotrophic fungi, and reactivated bacterial metabolic pathways and signaling networks that were suppressed by the pathogen. Taken together, our findings are consistent with a multi-tiered mode of action in which direct antagonism by B. mojavensis dxk33 operates alongside associated changes in the rhizosphere microbiome that resemble a disease-suppressive state, although the present experimental design does not allow a strictly causal role for microbiome reconfiguration in disease suppression to be established. This study provides a mechanistic framework for understanding how microbiome engineering may mitigate soil-borne diseases in perennial trees and highlights the potential of targeted microbial interventions for sustainable forest management. Full article

Cognitive deterioration and the transition to neurodegenerative disease does not develop through simple, linear regression; it develops as rapid and global transitions from one state to another within the neural network. Developing understanding and control over these events is among the largest tasks facing contemporary neuroscience. This paper will discuss a conceptual reframing of cognitive decline as a transitional phase of the functional state of complex neural networks resulting from the intertwining of molecular degradation, vascular dysfunction and systemic disarray. The paper will integrate the latest findings that have demonstrated how the disruptive changes in glymphatic clearance mechanisms, aquaporin-4 polarity, venous output, and neuroimmune signaling increasingly correlate with the neurophysiologic homeostasis landscape, ultimately leading to the destabilization of the network attraction sites of memory, consciousness, and cognitive resilience. Furthermore, the destabilizing processes are exacerbated by epigenetic silencing; neurovascular decoupling; remodeling of the extracellular matrix; and metabolic collapse that result in accelerating the trajectory of neural circuits towards the pathological tipping point of various neurodegenerative diseases including Alzheimer’s disease; Parkinson’s disease; traumatic brain injury; and intracranial hypertension. New paradigms in systems neuroscience (connectomics; network neuroscience; and critical transition theory) provide an intellectual toolkit to describe and predict these state changes at the systems level. With artificial intelligence and machine learning combined with single cell multi-omics; radiogenomic profiling; and digital twin modeling, the predictive biomarkers and early warnings of impending collapse of the system are beginning to emerge. In terms of therapeutic intervention, the possibility of reprogramming the circuitry of the brain into stable attractor states using precision neurointervention (CRISPR-based neural circuit reprogramming; RNA guided modulation of transcription; lineage switching of glia to neurons; and adaptive neuromodulation) represents an opportunity to prevent further progression of neurodegenerative disease. The paper will address the ethical and regulatory implications of this revolutionary technology, e.g., algorithmic transparency; genomic and other structural safety; and equity of access to advanced neurointervention. We do not intend to present a list of the many vertices through which the mechanisms listed above instigate, exacerbate, or maintain the neurodegenerative disease state. Instead, we aim to present a unified model where the phenomena of molecular pathology; circuit behavior; and computational intelligence converge in describing cognitive decline as a translatable change of state, rather than an irreversible succumbing to degeneration. Thus, we provide a framework for precision neurointervention, regenerative brain medicine, and adaptive intervention, to modulate the trajectory of neurodegeneration. Full article

A wide range of non-microbial contaminants—such as heavy metals, pesticide residues, antibiotics, as well emerging foodborne contaminants like micro- and nanoplastics and persistent organic pollutants—can enter the human body through daily diet and exert subtle yet chronic effects that are increasingly recognized to be gut microbiota-dependent. However, the relationships among multi-contaminant exposure profiles, dynamic microbial community structures, microbial metabolites, and diverse clinical or subclinical phenotypes are highly non-linear and multidimensional, posing major challenges to traditional analytical approaches. Artificial intelligence (AI) is emerging as a powerful tool to untangle the complex interactions between foodborne non-microbial contaminants, the gut microbiota, and host health. This review synthesizes current knowledge on how key classes of non-microbial food contaminants modulate gut microbial composition and function, and how these alterations, in turn, influence intestinal barrier integrity, immune homeostasis, metabolic regulation, and systemic disease risk. We then highlight recent advances in the application of AI techniques, including machine learning (ML), deep learning (DL), and network-based methods, to integrate multi-omics and exposure data, identify microbiota and metabolite signatures of specific contaminants, and infer potential causal pathways within “contaminant–microbiota–host” axes. Finally, we discuss current limitations, such as data heterogeneity, small-sample bias, and interpretability gaps, and propose future directions for building standardized datasets, explainable AI frameworks, and human-relevant experimental validation pipelines. Overall, AI-enabled analysis offers a promising avenue to refine food safety risk assessment, support precision nutrition strategies, and develop microbiota-targeted interventions against non-microbial food contaminants. Full article

Candida biofilms play a critical role in clinical settings, contributing to persistent and device-associated infections and conferring resistance to antifungal agents, particularly in immunocompromised or hospitalized patients. Biofilm formation varies among Candida species, including C. albicans and non-albicans species, such as C. glabrata, C. tropicalis, C. parapsilosis, and C. auris, due to species-specific transcriptional networks that regulate modes of biofilm development, extracellular matrix composition, and metabolic reprogramming. These differences influence biofilm responses to treatment and the severity of infections, which can be further complicated in polymicrobial biofilms that modulate colonization and virulence. Understanding the mechanisms driving biofilm formation and interspecies interactions is essential for developing effective therapies and requires appropriate experimental models. Available models range from simplified in vitro systems to more complex ex vivo and in vivo approaches. Static in vitro models remain widely used due to their simplicity and reproducibility, but they poorly mimic physiological conditions and require careful standardization. Ex vivo tissue models offer a balance between practicality and biological relevance, enabling the study of biofilm physiology, host–microbe interactions and immune responses. In vivo models, primarily in mice, remain the gold standard for testing antifungal therapies, while alternative systems such as Galleria mellonella larvae provide simpler, cost-effective approaches. Advanced in vitro platforms, including organ-on-chip systems, bridge the gap between simplified tests and physiological relevance by simulating fluid dynamics, tissue architecture, and immune complexity. This review aims to examine Candida biofilms across species, highlighting differences in structural diversity and clinical implications, and to provide a guide to the most widely used experimental models supporting studies on Candida biofilm biology for the development of new therapeutic targets or drug testing. Full article

Myopathy encompasses a group of diseases characterized by abnormalities in both muscle function and structure. However, the underlying regulatory mechanisms of newly formed myofiber development remain poorly defined. No promising therapeutic approach has been developed, but numerous medication options are available to alleviate symptoms. Our previous studies demonstrated that adenosine kinase (ADK) is critical in regulating adenosine metabolism, pathological angiogenesis, pathological vascular remodeling, and vascular inflammatory diseases. Adenosine dynamically distributes between extracellular and intracellular, and adenosine concentration regulates ADK expression. However, the mechanism by which adenosine triggers an ADK-dependent intracellular signaling pathway to regulate skeletal muscle regeneration is not well defined. This study aimed to evaluate whether the adenosine-induced intracellular signaling pathway is involved in regulating myopathy, and how it regulates the development of newly formed myofibers. In this study, an intramuscular injection of cardiotoxin was used to induce a skeletal muscle injury model; satellite cells and C2C12 cells were employed. Whether adenosine regulates satellite cell activity, new myofiber formation and differentiation, as well as fusion of myofibers, were determined by H&E staining, BrdU incorporation assay, and spheroid sprouting assay. Interaction between ADK and PFKFB3 was evaluated by IF staining, PPI network analysis, molecular docking simulation, and CO-immunoprecipitation assay. The results demonstrated that adenosine dynamically distributes between extracellular and intracellular through concentrative nucleoside transports or equilibrative nucleoside transporters, and it rapidly induces an ADK-dependent intracellular signaling pathway, which interacts with PFKFB3-mediated glycolytic metabolism to promote satellite cell activity, new myofiber formation, differentiation, and fusion, and eventually enhances skeletal muscle regeneration after injury stress. The remarkable endogenous regeneration capacity of skeletal muscle, which is regulated by adenosine-triggered intracellular signaling, presents a promising therapeutic strategy for treating muscle trauma and muscular dystrophies. Full article

Altitude-driven environmental changes influence the persistence of soil organic carbon (SOC) via microbial metabolic pathways. However, the degree to which the network robustness of microbial communities directly predicts the persistence of organic carbon in alpine mountain forests remains unclear. This study focused on the Qilian Sabina przewalskii forest, situated along an altitude gradient of 2900–3400 m in the Qilian Mountains, systematically exploring the organization of soil microbial communities, the co-occurrence networks’ robustness, and their predictive capacity for organic carbon storage. The results indicate that altitude, as a critical driving factor, not only alters the physicochemical properties, microbial composition, and diversity of the soil but also significantly impacts its complexity and network robustness. The complexity and robustness of the microbial network are highest in the mid-altitude region (3100–3200 m), which is conducive to the development of robust microbial networks. Both bacterial α diversity and network robustness exhibit positive correlations with SOC, whereas fungal diversity shows a negative correlation with SOC. Furthermore, statistical modeling revealed that indices of microbial co-occurrence network robustness were stronger predictors of SOC storage than classical alpha-diversity indices. The structural equation model reveals that microbial biomass nitrogen (MBN) serves as a key mediating factor linking microbial diversity and SOC. Soil characteristics emerge as the primary direct driving factor, whereas the robustness of microbial networks exerts a significant yet minor direct and mediating influence. This study underscores that the robustness of microbial networks, rather than their diversity, is a critical predictor of soil organic carbon in high-altitude mountain forests. It offers a novel theoretical framework for understanding the mechanisms of the carbon cycle in mountain forest ecosystems in the context of climate warming. Full article

Cold stress limits cucumber productivity, and grafting onto tolerant rootstocks offers a promising strategy for improving resilience. This study compared the responses of cucumber heterografts and self-grafts exposed to different cold temperatures, aiming to uncover the molecular basis of grafting-mediated tolerance. Morphological observations showed that grafting onto Cucurbita ficifolia and C. maxima X C. moschata cv. Tetsukabuto rootstocks improved plant growth under moderate cold, while extreme stress remained lethal. Transcriptome analysis revealed that heterografts displayed broader and more sustained differentially expressed genes than self-grafts. Gene ontology (GO) enrichment in heterografts indicated early activation of structural, regulatory, and metabolic processes, with continued enrichment at later stages. KEGG analysis highlighted plant hormone signaling as a central pathway modulated by heterografting, with selective regulation of auxin, ethylene, and ABA signaling. Heterografts activated key regulators, including MAPK3-like, TIFY5A, and CPK28, which were strongly expressed, alongside transcription factors from NAC, CAMTA, WRKY, and MYB families, suggesting coordinated regulation of cold-responsive networks. These results demonstrate that heterografting enhances cold tolerance by orchestrating multi-layered molecular responses, including hormone modulation, stress signaling, and transcriptional factors. This underscores the potential of grafting onto cold-tolerant rootstocks as a practical strategy for cucumber cultivation in cold-prone environments. Full article

Veraison represents a pivotal transition point in grape berry ripening, driven by a cascade of temporally coordinated physiological and molecular events. Studies have shown that the onset of veraison is initially triggered by a decline in cell turgor, regulated by osmotic potential and water status, which subsequently leads to fruit softening. This softening process is accompanied by extensive cell wall remodeling, establishing a structural basis for enhanced sugar influx. A rapid accumulation of sugars follows, acting not only as metabolic substrates but also as signaling molecules that synergize with abscisic acid (ABA) to activate transcriptional programs, including the induction of anthocyanin biosynthesis that drives skin color change. ABA accumulates at the early stages of veraison and functions as a key hormonal regulator initiating the ripening process. In contrast, auxin (IAA) and gibberellin (GA) levels decline prior to veraison, thereby releasing their inhibitory effects on ripening. Environmental factors such as water availability, light, and temperature significantly influence the timing and intensity of veraison by modulating hormonal signaling pathways. The initiation of grape berry ripening exemplifies a multilayered regulatory network that progresses through turgor signaling, hormonal regulation, metabolic reprogramming, and transcriptional activation, thereby providing a mechanistic framework for understanding non-climacteric fruit ripening. offering a mechanistic framework for understanding non-climacteric fruit ripening. This review provides an integrated perspective on the initiation mechanism of veraison, offering theoretical insights and practical implications for improving grape quality and vineyard management. Full article

Background and Objectives: Infantile spasms (ISs), or West syndrome (WS), represent an early-onset epileptic encephalopathy in which diverse structural, genetic, metabolic, infectious, and neurocutaneous conditions converge on a shared pattern of hypsarrhythmia, clustered spasms, and later developmental impairment. Growing use of genomic diagnostics has revealed that variants in STXBP1, KCNQ2, GRIN2A, GRIN2B, and TSC-related genes are more common than previously recognized and can be linked to partially actionable pathways. This review aimed to synthesize current evidence on the multifactorial etiology, network-based pathogenesis, and evolving targeted therapies for ISs, with particular attention to TSC-related forms. Materials and Methods: A structured narrative review was undertaken of publications from 1990 to 2025 in PubMed, Scopus, Web of Science, and Embase using terms related to ISs, WS, genetics, mTOR, ACTH, vigabatrin, ketogenic diet, and precision therapies. Authoritative guidance from ILAE and AAN was incorporated. Clinical, molecular, and therapeutic data were grouped under etiological, pathogenetic, and management domains. Results: Structural causes remained the largest group, but combined genetic, genetic–structural, and metabolic etiologies accounted for about one third of contemporary cohorts. Early network disruption involving cortex, thalamus, basal ganglia, and brainstem, together with imbalances in NGF, BDNF, and IGF-1, explained why distinct primary insults produce a uniform electroclinical phenotype. Early treatment with ACTH or high dose prednisolone, with or without vigabatrin, was consistently associated with higher electroclinical remission and better developmental outcome. Everolimus and related mTOR inhibitors showed benefit in TSC-associated ISs, while agents directed at NMDA receptors or KCNQ channels are emerging for genotype defined subgroups. Conclusions: ISs should be approached as a heterogeneous but mechanistically convergent disorder in which rapid diagnosis, parallel genetic testing, and early disease modifying therapy improve prognosis. Integration of molecular profiling with standardized outcome monitoring is likely to move management from symptomatic seizure control to pathway-specific intervention. Full article

Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article

The AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest transcription factor families in plants and is not only vital for plant growth and development but also participates in responding to various abiotic stresses. However, few studies have investigated the function of the AP2/ERF gene family in natural rubber (NR) biosynthesis in Hevea brasiliensis. Here, 174 HbAP2/ERF genes were identified genome-wide and classified into 18 subclades based on gene-conserved structure and phylogenetic analysis. Gene duplication analysis revealed that 7 tandem and 100 segmental duplication events were major drivers of this gene family. Cis-element analysis in HbAP2/ERF promoters identified light-, hormone-, stress-, and development-associated cis-elements. Tissue-specific expression profiles revealed that 160 HbAP2/ERFs were expressed in at least one tissue. The protein–protein interaction network identified 59 potential interactions among the HbAP2/ERFs. Critically, dual-luciferase reporter assays confirmed that two key regulators exhibit distinct regulatory modes on NR biosynthesis-related genes: HbAP2/ERF25 significantly repressed the transcriptional activities of HbMVD1, HbCPT7, and HbSRPP1, whereas HbAP2/ERF46 repressed HbMVD1 but activated HbHMGR1, HbFPS1, and HbSRPP1. These findings reveal the complex regulatory network of HbAP2/ERFs in NR biosynthesis, establish a comprehensive framework for understanding their evolution and functional diversification, and provide novel molecular targets for genetic improvement of NR yield in rubber tree breeding and metabolic engineering. Full article

Pork is one of the most widely consumed meats worldwide, with tenderness and intramuscular fat (IMF) content serving as key determinants of consumer acceptance. The rising demand for high-quality pork underscores the need to better understand the molecular mechanisms regulating IMF deposition and meat tenderness. In this study, we systematically examined the tenderness and IMF in the Longissimus dorsi (LD) muscle of 104 eight-month-old Songliao black pigs and Leixiang pigs raised under identical conditions. In addition, three pigs from each breed were randomly selected for multi-omics analyses, including Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), transcriptomics, and proteomics to elucidate the molecular networks underlying IMF deposition and tenderness. We identified a total of 2635 differentially accessible chromatin (DARs) regions associated with 2006 functional genes and 351 regulatory transcription factors, predominantly enriched in adipocyte differentiation and muscle metabolism pathways. Transcriptome analysis revealed 624 differentially expressed genes (DEGs) involved in lipid metabolism and tissue structure maintenance. While proteomic profiling detected 153 differentially expressed proteins (DEPs) enriched in fatty acid degradation/metabolism, PPAR signaling, energy metabolism, and thermogenesis pathways. Further, combined integrated multi-omics analysis identified nine candidate genes (MBP, DCLK1, COL3A1, ART3, COL14A1, PDK4, VCAN, LIPE, and GPX1) and transcription factor–target interaction networks predicted key regulatory factors including MEF2A/C/D, PR, GR, AR-HALLSITE, NF1-HALLSITE, AP4, TCF21, MYOG, ATOH1, TCF12, BHLHA15, MYF5, ASCL1, and SIX2, which were potentially involved in the regulation of meat tenderness and IMF deposition. These findings provide novel insights into the molecular determinants of IMF and tenderness, offering valuable targets for improving meat quality through genetic breeding strategies. Full article

Phenylalanine ammonia-lyase (PAL) is the core branch-point enzyme connecting plant primary aromatic amino acid metabolism to the phenylpropanoid pathway, which determines carbon flux redistribution between growth and defense and is essential for plant adaptation to various environments. Extensive research has clarified PAL’s conserved homotetrameric structure, MIO cofactor-dependent catalytic mechanism, and its roles in plant growth, development, and stress responses. However, there is a lack of comprehensive review studies focusing on PAL-mediated carbon metabolic flux redistribution, specifically covering its structural and evolutionary foundations, the links between this flux regulation and plant growth/development, its multi-layered regulatory network, and its roles in stress adaptation, limiting a comprehensive understanding of its evolutionary and functional diversity. This review systematically covers four core aspects: first, the molecular foundation, encompassing PAL’s structural features and catalytic specificity governed by the MIO cofactor; second, evolutionary diversity spanning from algae to angiosperms, with emphasis on unique regulatory mechanisms and evolutionary significance across lineages; third, the multi-layered regulatory network, integrating transcriptional control, post-translational modifications, epigenetic regulation, and functional crosstalk with phytohormones; and fourth, functional dynamics, which elaborate PAL’s roles in organ development, including root lignification, stem mechanical strength, leaf photoprotection, flower and fruit quality formation, and lifecycle-wide dynamic expression, as well as its mediated stress adaptations and regulatory networks under combined stresses. These insights provide a theoretical basis for targeted manipulation of PAL to optimize crop carbon allocation, thus improving growth performance, enhance stress resilience, and promote sustainable agriculture. Full article

Dark fermentative hydrogen production is constrained by challenges including low hydrogen yield and operational instability. Magnetic nanoparticles (MNPs) have emerged as promising additives for enhancing biohydrogen production due to their unique physicochemical characteristics, such as high specific surface area, excellent electrical conductivity, and inherent magnetic recyclability. This review systematically compares the enhancement mechanisms of MNPs in two distinct microbial systems: pure cultures and mixed cultures. In pure cultures, MNPs function primarily at the cellular and molecular levels through the following: (1) serving as sustained-release sources of essential metallic cofactors like Fe and Ni to promote hydrogenase synthesis and activation; (2) acting as efficient electron carriers that facilitate intracellular and extracellular electron transfer; and (3) redirecting central carbon metabolism toward high-hydrogen-yield acetate-type fermentation. In mixed cultures, which are more representative of practical applications, MNPs operate at the ecological level through the following: (1) modifying microenvironmental niches to exert selective pressure that enriches hydrogen-producing bacteria, such as Clostridium; (2) forming conductive networks that promote direct interspecies electron transfer and strengthen syntrophic metabolism; and (3) enhancing system robustness via toxin adsorption and pH buffering. Despite promising phenomenological improvements, critical knowledge gaps remain, including unclear structure–activity relationships of MNPs, insufficient quantification of electron transfer pathways, unknown genetic regulatory mechanisms, and overlooked magnetobiological effects. Future research should integrate electrochemical monitoring, multi-omics analyses, and advanced characterization techniques to deepen the mechanistic understanding of nanomaterial–microbe interactions. This review aims to provide theoretical insights and practical strategies for developing efficient and sustainable MNP–microorganism hybrid systems for scalable biohydrogen production. Full article