Search Results (263)

Resilience is commonly framed as a psychological trait, yet clinical and experimental evidence demonstrates that resilience failures emerge concurrently across metabolic, endocrine, immune, and cognitive domains. This review examines resilience as a bioenergetic property constrained by how organisms allocate finite metabolic resources under stress. We synthesize evidence from endocrinology, mitochondrial biology, immunometabolism, and stress physiology to propose a parsimonious, hypothesis-driven Energy Allocation System (EAS) in which the hypothalamic-pituitary-adrenal (HPA), thyroid (HPT), and gonadal (HPG) axes are conceptualized as a coordinated energy-governance network. Despite extensive investigation within these individual fields, the literature lacks an integrative physiological framework explaining why multisystem stress responses co-occur in predictable endocrine and metabolic patterns. Within this framework, mitochondrial reserve capacity serves as the limiting substrate through which hormonal signals regulate mobilization, metabolic pacing, immune tolerance, and recovery. The reviewed literature supports predictable patterns of endocrine reorganization during energetic strain, including prioritization of glucocorticoid-mediated mobilization, constrained thyroid hormone activation, suppression of long-term anabolic investment, and impaired recovery following stress. These configurations reflect adaptive energy-conserving strategies rather than isolated organ dysfunction. The novelty of this review lies in organizing established biological mechanisms into a unified, energy-allocation-based framework that generates falsifiable predictions linking endocrine coordination to bioenergetic capacity and recovery dynamics. We further discuss how routinely available biomarkers and validated psychometric measures can be interpreted as functional readouts of energetic allocation rather than static disease markers. Framing resilience through coordinated energy governance offers a unifying mechanistic lens for interpreting multisystem stress responses and generates testable predictions for future experimental and clinical investigation. Full article

The gut microbiome is defined as the collective assembly of microbial communities inhabiting the gut, along with their genes and metabolic products. The gut microbiome systematically regulates host metabolism, immunity, and neuroendocrine homeostasis via interspecies interaction networks and inter-organ axes. Given the importance of the gut microbiome to the host, this review integrates the composition, function, and genetic basis of the gut microbiome with host genomics to provide a systematic overview of recent advances in microbiome–host interactions. This encompasses a complete technological pipeline spanning from in vitro to in vivo models to translational medicine. This technological pipeline spans from single-bacterium CRISPR editing, organoid–microbiome co-culture, and sterile/humanized animal models to multi-omics integrated algorithms, machine learning causal inference, and individualized probiotic design. It aims to transform microbiome associations into precision intervention strategies that can be targeted and predicted for clinical application through interdisciplinary research, thereby providing the cornerstone of a new generation of precision treatment strategies for cancer, metabolic, and neurodegenerative diseases. Full article

The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of injury. This review summarizes principles of ECM organization, mechanotransduction, and pathological remodeling and highlights translational opportunities for ECM-targeted therapies, biomaterial platforms, and precision diagnostics. We conducted a narrative synthesis of foundational and recent literature covering ECM composition and turnover, stiffness-dependent signaling, and disease-associated remodeling across fibrosis/cardiovascular disease, cancer, and metabolic disorders, together with advances in ECM-based biomaterials, drug delivery, and ECMderived biomarkers and imaging. Across organs, a self-reinforcing cycle of altered matrix composition, excessive crosslinking, and stiffness-dependent mechanotransduction (including integrin–FAK and YAP/TAZ pathways) sustains fibroinflammation, myofibroblast persistence, and progressive tissue dysfunction. In tumors, aligned and crosslinked ECM promotes invasion, immune evasion, and therapy resistance while also shaping perfusion and drug penetration. Translational strategies increasingly focus on modulating ECM synthesis and crosslinking, normalizing rather than ablating matrix architecture, and targeting ECM–cell signaling axes in combination with anti-fibrotic, cytotoxic, or immunotherapeutic regimens. ECM biology provides a unifying framework linking pathogenesis, therapy, and precision diagnostics across chronic diseases. Clinical translation will benefit from standardized quantitative measures of matrix remodeling, mechanism-based biomarkers of ECM turnover, and integrative imaging–omics approaches for patient stratification and treatment monitoring. Full article

The aim of this study is to systematically capture, synthesize, and evaluate current research trends related to Automated Multiple-Choice Question Generation as they emerge within the broader landscape of natural language processing (NLP) and large language model (LLM)-based educational and assessment research. A systematic search and selection process was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using predefined inclusion and exclusion criteria. A total of 240 eligible publications indexed in the Scopus database were identified and analyzed. To provide a comprehensive overview of this evolving research landscape, a bibliometric analysis was performed utilizing performance analysis and scientific mapping methods, supported by the Bibliometrix (version 4.2.2) R package and VOSviewer (version 1.6.19) software. The findings of the performance analysis indicate a steady upward trend in publications and citations, with significant contributions from leading academic institutions—primarily from the United States—and a strong presence in high quality academic journals. Scientific mapping through co-authorship analysis reveals that, despite the increasing research activity, there remains a need for enhanced collaborative efforts. Bibliographic coupling organizes the analyzed literature into seven thematic clusters, highlighting the main research axes and their diachronic evolution. Furthermore, co-word analysis identifies emerging research trends and underexplored directions, indicating substantial opportunities for future investigation. To the best of our knowledge, this study represents the first systematic bibliometric analysis that examines Automated Multiple-Choice Question Generation research within the context of the broader LLM-driven educational assessment literature. By mapping the relevant scientific production and identifying research gaps and future directions, this work contributes to a more coherent understanding of the field and supports the ongoing development of research at the intersection of generative AI and educational assessment. Full article

Background: In nuclear medicine, numerous cancer types are treated via internal irradiation with radiopharmaceuticals, including low-LET (linear energy transfer) beta-emitting radionuclides like Lu-177. In most cases, such treatments lead to low-dose exposure of organ systems with β-irradiation, which induces only few isolated DSBs (double-strand breaks) in the nuclei of hit cells, the most threatening DNA damage type. That damaging effect contrasts with the clustering of DNA damage and DSBs in nuclei traversed by high-LET particles (α particles, ions, etc.). Methods: After in-solution β-irradiation for 1 h with Lu-177 leading to an absorbed dose of about 100 mGy, we investigated the spatial nano-organization of chromatin at DSB damage sites, of repair proteins and of heterochromatin marks via single-molecule localization microscopy (SMLM) in PBMCs. For evaluation, mathematical approaches were used (Ripley distance frequency statistics, DBScan clustering, persistent homology and similarity measurements). Results: We analyzed, at the nanoscale, the distribution of the DNA damage response (DDR) proteins γH2AX, 53BP1, MRE11 and pATM in the chromatin regions surrounding a DSB. Furthermore, local changes in spatial H3K9me3 heterochromatin organization were analyzed relative to γH2AX distribution. SMLM measurements of the different fluorescent molecule tags revealed characteristic clustering of the DDR markers around one or two damage foci per PBMC cell nucleus. Ripley distance histograms suggested the concentration of MRE11 molecules inside γH2AX-clusters, while 53BP1 was present throughout the entire γH2AX clusters. Persistent homology comparisons for 53BP1, MRE11 and γH2AX by Jaccard index calculation revealed significant topological similarities for each of these markers. Since the heterochromatin organization of cell nuclei determines the identity of cell nuclei and correlates to genome activity, it also influences DNA repair. Therefore, the histone H3 tri methyl mark H3K9me3 was analyzed for its topology. In contrast to typical results obtained through photon irradiation, where γH2AX and H3K9me3 markers were well separated, the results obtained here also showed a close spatial proximity (“co-localization”) in many cases (minimum distance of markers = marker size), even with the strictest co-localization distance threshold (20 nm) for γH2AX and H3K9me3. The data support the results from the literature where only one DSB induced by low-dose low LET irradiation (<100 mGy) can remain without heterochromatin relaxation for subsequent repair. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

The concept of intersectionality examines how multiple and interdependent forms of oppression manifest among marginalized social groups, considering their social markers. This study aims to analyze intersectionality in the labor market, with a critical focus on the interactions between race, gender, and class as structuring axes of inequality. An integrative literature review was conducted, encompassing an in-depth analysis of 140 articles addressing intersectionality in the labor context. The findings reveal a persistent conceptual fragmentation of intersectionality and a dilution of critical debates within labor market research. Empirical evidence consistently shows that women and racialized groups face enduring structural barriers, including wage gaps, occupational segregation, and limited access to leadership positions. Moreover, these inequalities are often obscured or reduced to superficial diversity and inclusion initiatives rather than being addressed as systemic issues. The study emphasizes the importance of committed and critical intersectional approaches to understanding and addressing systemic inequalities in the labor market, highlighting theoretical and epistemological gaps that must be addressed to advance emancipatory practices and policies that directly confront structural racism, patriarchy, and class-based exploitation. The study contributes theoretically by deepening the application of intersectionality in the labor market and by identifying conceptual and epistemological gaps in the literature. Empirically, it provides practical guidance for organizations to transform diversity initiatives into strategic and inclusive actions, integrating multiple social identities into management policies and practices. Full article

Ionizing radiation remains the primary approach for treating brain cancer and is frequently used in combination with chemotherapy. However, when it comes to gliomas, the effective delivery of therapeutic agents is hindered by the limited permeability of the blood–brain barrier (BBB). Consequently, selecting the most suitable and least harmful type of ionizing radiation is essential, given its potential side effects on healthy cells within the tumor microenvironment. In this study, we explored the impact of X-ray exposure on two in vitro BBB endothelial cell models—murine and human. Post-irradiation, we evaluated cell viability, clonogenic capacity, cell cycle progression, reactive oxygen species (ROS) levels, formation of micronuclei and γ-H2AX foci, as well as alterations in cytoskeletal organization, cell migration, and intracellular calcium dynamics. The results demonstrate notable differences between the two endothelial cell lines, suggesting the human cell line is more sensitive to X-rays. In conclusion, our study provides valuable insights into the brain microvascular endothelial cells’ response to radiation, laying the groundwork for strategies to protect healthy brain tissue. Full article

Background: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs used in type 2 diabetes mellitus management, and they have associated cardiovascular and renal advantages beyond their glucose-lowering effects, with maintained proof linking gut microbiota modulation to their multiple therapeutic benefits. Aim: This review aims to deliver an overview of the current knowledge regarding the relationship between SGLT-2 inhibitors and the gut microbiota and how this interplay impacts the gut–organ axes such as the lung, heart, brain, liver, and hematological system. Methodology: A literature review was performed in Web of Science, PubMed, and Google Scholar to discover studies that assessed the effects of SGLT-2 inhibitors on gut microbiota composition, microbial metabolites, and associated systemic consequences. Results: SGLT-2 inhibitors modulate gut microbiota and its driven metabolites, strengthening the barrier integrity and alleviating endotoxemia, inflammation, and oxidative stress, resulting in beneficial outcomes across the different gut–organ axes. Conclusion: Gut microbiota modulation is an emerging approach in mediating the multifaceted beneficial impacts of SGLT-2 inhibitors, revealing that their effectiveness goes beyond glycemic control. Future research should concentrate on the microbial taxa and metabolites that mediate these impacts and testing combination approaches that target SGLT-2 pathways and gut microbiota to enhance preservation of different organs. Full article

Angiosperms include many taxa with dimorphic unisexual reproductive structures. These are well studied in some grasses, with maize as a key model, but other wind-pollinated lineages in Poales remain less explored. Within Poales, the family Restionaceae has the highest known proportion of dioecious species. In its Australian subfamily Leptocarpoideae, the sexually dimorphic Leptocarpus denmarkicus has raised questions about the basic flowering unit and the developmental basis of dimorphism. Here, we analyze inflorescence architecture and floral development in Eurychorda complanata, the sister lineage to the remainder of Leptocarpoideae. Using comparative morphology, light microscopy and scanning electron microscopy, we reconstruct synflorescence topology, floral organography, and ontogeny in both sexes and compare them with those in L. denmarkicus. In Eurychorda, both sexes produce polytelic paniculate synflorescences with distinct inhibition zones and many-flowered simple spikelets as the basic flowering unit. Male and female spikelets bear up to 50 and up to 15 fertile flowers, respectively. Male flowers have two stamens and a dimerous pistillode, whereas female flowers possess two long filamentous staminodes and a dimerous gynoecium. Ontogenetic series show that flowers of both sexes initiate both androecial and gynoecial structures, and that functional unisexuality is achieved through late arrest of the organs of one sex. Defining spikelets as racemose axes with lateral sessile flowers clarifies homologies of reproductive structures and supports reinterpretation of the dimorphic female unit in L. denmarkicus as a derived compound spike generated through shifts in branching rank and the timing of lateral initiation. The compound female spike of L. denmarkicus has a striking overall similarity to the simple female spikelet in Eurychorda, illustrating fascinating parallelism in the evolution of reproductive organs within Restionaceae and Poales more broadly. At the male side, Eurychorda achieves anther exsertion via filament elongation, whereas in L. denmarkicus filaments are very short and anthers remain within the perianth, but male spikelets sit on long, flexible peduncles that invert the spikelet and promote trembling, thereby ventilating the perianth chamber and aiding pollen escape. These two solutions—filament elongation versus spikelet-peduncle flexibility—represent alternative strategies of pollen release in wind-pollinated flowers. 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

The SNF2-related chromatin remodeler Srcap is the principal ATPase responsible for the deposition of the histone variant H2A.Z at promoters and regulatory chromatin regions. Although this activity is known to modulate transcription, its contribution to DNA replication remains unexplored. Here we show that Srcap is required for efficient replication fork progression and origin firing in mammalian cells. Using RNA interference in human PC3 cells, we found that Srcap depletion leads to a ~25% reduction in fork elongation rate, decreased replication fork density, accumulation of the replication-stress marker γH2AX, and reduced chromatin-bound H2A.Z. High-resolution expansion microscopy further revealed diminished intensity and increased spacing of replication foci, consistent with reduced origin activation. Transcriptomic analysis of published data identified broad downregulation of replication-associated genes. These data uncover a dual mechanism by which Srcap sustains replication efficiency—through both H2A.Z-dependent chromatin organization and transcriptional maintenance of the replication machinery. Our findings establish Srcap as an important coordinator of replication dynamics, with implications for genome stability. Full article

Background: Malignant ovarian tumours are most often detected at an advanced stage, when peritoneal dissemination across abdominal organs is already present. Metastasis in ovarian cancer arises from complex interactions between cancer cells and diverse components of the tumour microenvironment (TME), including extracellular matrix elements, fibroblasts, adipocytes, mesenchymal cells and leukocytes. This dynamic niche drives tumour progression, invasiveness and immunosuppression through cytokine- and chemokine-mediated signalling. A deeper understanding of these interactions may enable targeted modulation of the TME and help limit metastatic spread. Methods: In this study, using immunoenzymatic assays and a computational digital twin—a mechanistic, ODE-based in silico model that replicates key cellular and microenvironmental processes—we investigated whether and how caffeic acid phenethyl ester (CAPE) influences TME activation, cytokine and growth factor levels, and extracellular matrix remodelling. Results: Our findings show that CAPE modulates both pro- and antitumourigenic signalling pathways across immune, stromal and hypoxia-related axes, suggesting its potential to reshape the ovarian cancer microenvironment and improve therapeutic outcomes in this challenging malignancy. Conclusions: Taken together, these results indicate that CAPE may serve as a multifaceted modulator capable of simultaneously targeting tumour cells and their microenvironment, offering a promising avenue for enhancing therapeutic strategies in ovarian cancer. Full article

The microbiota–gut–organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson’s disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota–gut–organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation. Full article

Boron (B) remains one of the least understood trace elements in human nutrition. Traditionally regarded as non-essential, its biological role has been reevaluated in light of emerging microbiome research. We provide a narrative synthesis of mechanistic, preclinical, and clinical studies to assess whether the colonic actions of B meet accepted criteria for nutritional essentiality. This review revisits B bioavailability through a dual-pathway framework distinguishing plasma-accessible boron (PAB)—small, fully absorbable species with transient systemic effects—from microbiota-accessible boron complexes (MABCs)—indigestible conjugates that reach the colon intact. Evidence indicates that PAB exerts short-term metabolic modulation, whereas MABCs act as prebiotic cofactors that stabilize microbial quorum sensing (autoinducer-2–borate; AI-2B), reinforce the colonic mucus barrier through borate–diol crosslinking, and support host–microbiota symbiosis. Deficiency or low intake of MABCs leads to dysbiosis, barrier fragility, and low-grade inflammation along gut–organ axes—effects reversible by MABC-rich diets. Analytical and clinical tools are proposed to discriminate between PAB and MABC pathways, including fecal B/speciation, AI-2B assays, and mucus-penetration markers. Recognizing B’s essentiality as a microbiota-dependent nutrient reframes its nutritional assessment, guiding future dietary guidelines and prebiotic design toward the microbiome–mucus interface. Full article