Abstract: Caño Barro is a secondary tributary of the Ayapel wetland complex (Ramsar site), Córdoba, Colombia. Despite its role connecting the Cauca River to the wetland, no previous study has assessed its environmental condition. This work presents an integrated geo-environmental evaluation combining morphometric analysis, in-situ water quality measurements, and total mercury (Hg-T) analysis across ten stations. The watershed (632.78 km2, Kc = 2.09) has a very low channel slope (0.017%), limiting sediment transport. Dissolved oxygen fell below 4.0 mg/L at three stations (P1 = 3.55, P3 = 2.58, P6 = 3.27 mg/L), indicating localized oxygen depletion. Hg-T exceeded the US EPA chronic criterion (CCC = 0.77 µg/L) at six of seven quantifiable stations (range: 0.54–2.01 µg/L), with one outlier of 97.46 µg/L requiring confirmation. The Conesa impact assessment classified mercury ecotoxicity as severe (I = −66), ranking it as the highest management priority. Conservation proposals include riparian restoration, erosion control, and mercury monitoring. These results provide the first environmental baseline for this Ramsar tributary and underscore the impacts of illegal gold mining on protected wetland systems.

Abstract: Cement manufacturing is one of the major sources of carbon dioxide (CO2) emissions globally. Cement replacement materials are increasingly used to minimize the environ-mental impact of concrete production. In the present study, the mechanical and envi-ronmental performance of concrete mixtures containing fly ash and recycled glass powder as partial cement replacements at levels of 10%, 20%, and 30% were investigated. Workability, unit weight, compressive strength, and water permeability tests were con-ducted to evaluate the effect of replacements on the behavior of concrete. Carbon emissions and performance-normalized indicators were applied to evaluate environmental performance. It was observed that as the replacement level increased, the carbon emis-sions decreased. The highest reduction was observed at the 30% replacement level, as 28.9%. Compressive strength varied between 21.9 and 27 MPa. This indicates that all mixtures met the targeted strength range. The mixture with 30% fly ash demonstrated the highest environmental efficiency, with a carbon intensity of 10.84 kg CO₂/MPa. This in-dicates a 19.2% reduction compared to the control mixture. The sensitivity analysis re-vealed that changes in emission factors did not alter the order of the mixture.

Abstract:

Bacillus thuringiensis subsp. israelensis (Bti) is the most widely used biological larvicide for mosquito control worldwide and a cornerstone of environmentally sustainable vector-management programs. Its long-term global deployment reflects a well-characterized balance between public-health benefit and manageable ecological tradeoffs within integrated vector management (IVM) frameworks. Bti combines high larvicidal efficacy, operational simplicity, and strong target specificity, resulting in an exceptional safety profile for humans and vertebrate wildlife. Decades of laboratory and field studies demonstrate that Bti is biologically selective rather than ecologically inert, with reproducible yet context-dependent effects confined to closely related non-target aquatic dipterans. This review links the molecular and toxicological foundations of Bti to its operational performance, ecological selectivity, resistance-mitigating properties, and sustained utility in mosquito-control programs. Beyond its established larvicidal function, Bti’s prokaryotic insect larvicidal organelle (PILO) represents an underexplored platform for heterologous intracellular protein assembly. Its dense packing, structural stability, and resistance to environmental and biochemical stress indicate an evolutionary specialization for high-capacity protein storage during sporulation. These properties support noncanonical applications in biomolecule storage and stabilization and motivate cautious exploration of environmentally responsive protein release strategies. Although significant mechanistic and translational challenges remain, particularly with respect to cargo trafficking, modularity, and purification, the architectural principles that have enabled effective mosquito control provide a strong foundation for extending PILO-based platforms beyond larvicidal applications.

Abstract: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant widely detected in aquatic ecosystems, but its subcellular targets and the mechanisms by which it disrupts light resource utilization in photosynthetic protozoa remain poorly understood at environmentally relevant concentrations. Here, Euglena gracilis was exposed to environmentally relevant PFOS concentrations. Subcellular distribution, phototaxis, photosynthetic light reactions, and energy metabolism were investigated using isolated chloroplast assays, transcriptomics, and proteomics. PFOS accumulated prominently in the eyespot and chloroplasts. Eyespot accumulation impaired phototactic motility and increased the light perception threshold. PFOS did not acutely inhibit overall photosynthesis; instead, a transient upregulation of photosynthesis-related genes and a slight stimulation of oxygen evolution were observed, which weakened with prolonged exposure. PFOS significantly reduced ATP levels and the photosynthetic electron transport rate (ETR), while Fv/Fm remained unchanged and non photochemical quenching (NPQ) was elevated. Isolated chloroplast assays confirmed direct inhibition of Mg²⁺ ATP synthase and thylakoid electron transport. Transcriptomic and proteomic analyses revealed compensatory upregulation of photosynthesis pathways but suppression of ATP synthesis and redox homeostasis. Mechanistically, PFOS directly targets chloroplast ATP synthase, leading to proton gradient accumulation, feedback inhibition of electron transport, and increased NPQ. Together with eyespot mediated phototaxis impairment, PFOS dually disrupts light acquisition (behavioral) and light conversion (physiological). This dual impairment may compromise the ecological fitness of Euglena in PFOS contaminated environments, especially under prolonged exposure.

Abstract: Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools - such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling – that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and on optimizing treatment sequencing across adjuvant and neoadjuvant settings.

Abstract:

The Koide relation \( Q = (\sum m_\ell)/(\sum \sqrt{m_\ell})^2 = 2/3 \) for the charged leptons has held to one part in \( 10^5 \) for over forty years without an accepted derivation and is widely regarded as numerology. This paper takes the relation as a clue rather than an endpoint. Treating lepton mass square roots as Descartes-circle curvatures, the outer root of the Descartes quadratic equals the closed form \( \mathcal{F} = e_1 - \sqrt{p_2} \) when Koide holds exactly (Proposition 1); equivalently, \( \mathcal{F}^2 = \alpha_K^2\,\mu_\star \) with \( \alpha_K^2 = 5/2 - \sqrt{6} \) and \( \mu_\star = \sum_\ell m_\ell \) the lepton-sum scale. The three-input symmetric-polynomial identity thus collapses to one dimensionless Koide-determined constant times the lepton-sum scale. Kocik [1] first observed a Descartes-like reading of Koide; our mutually-tangent variant is mathematically distinct but follows the same geometric spirit. The four-curvature completion carries a testable consequence absent from the bare three-mass relation: evaluating the squared fourth curvature numerically, \( \mathcal{F}^2 = 95.113 \) MeV, and comparing against the strange-quark \( \bar{MS} \) mass at \( \mu_\star \) within current lattice precision yields a residual of \( +0.04 \) MeV against \( \pm 0.69 \) MeV, about \( +0.06\sigma \). The lepton-side quantity is fixed to better than \( 0.01\% \); future lattice improvements will sharpen or refute the present numerical agreement. To our knowledge this paper implements the first Monte Carlo null test of the Koide relation under a random-spectrum prior; a Koide-conditioned null-model calibration across four prior shapes pre-registered for the analysis gives hit fractions at the sub-percent level — model-conditional frequencies, not \( p \)-values. Scale, input, prior, and filter sensitivities, together with the error budget, are reported; full Monte Carlo protocols, numerical output, and pre-registration are in a companion methods note [2].

Abstract: Exploring a possibility of β-myrcene (MY) incorporation in propene copolymerization has been studied in the presence of phenoxide-modified half-titanocene, Cp’TiCl₂(O-2,6-ⁱPr₂-4-C₆H₃) (Cp’ = Cp*, Me₃SiC₅H₄), and ketimide-modified half-titanicene, Cp’TiCl₂(N=C^tBu₂) (Cp’ = Cp*, Cp), catalysts. The permethylated Cp* catalysts exhibited good catalytic activities in the copolymerizations but afforded the copolymers up to 3 mol% MY incorporation; the other catalysts showed the negligible activities. The resulting copolymers were amorphous and exhibited glass transition temperatures (T_g) that de-creased with increasing the comonomer (MY) content, reaching values as low as −17 °C.

Abstract: Background: Tuberculosis remains a leading cause of infectious disease mortality, with over 10 million new cases annually. The standard first-line regimen—isoniazid, rifampicin, pyrazinamide, and ethambutol—has dramatically improved survival, yet drug-induced micronutrient depletion, particularly zinc, is an underappreciated complication that may contribute to treatment-related morbidity. Ethambutol-induced optic neuropathy (EON) affects 1–5% of treated patients, and accumulating evidence implicates zinc chelation as its central mechanism. We hypothesize that anti-TB therapy creates a “multi-hit” zinc depletion state through convergent drug- and disease-mediated pathways.Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and Cochrane databases from 1944 (discovery of streptomycin) through March 2026. Search terms combined anti-TB drug names with zinc, copper, micronutrient, optic neuropathy, and visual loss. We included randomized controlled trials, cohort studies, case-control studies, case series, in vitro investigations, and animal models. PRISMA 2020 guidelines were followed. Risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane RoB 2.0 tool for trials.Results: From 2,847 initial records, 186 studies met inclusion criteria. Serum zinc was significantly lower in TB patients versus controls (pooled mean difference: −12.1 μmol/L; 95% CI: −14.5 to −9.7; I² = 68%). Ethambutol directly chelates zinc and copper in retinal ganglion cells via its metabolite EDBA, causing lysosomal membrane permeabilization and mitochondrial dysfunction. Isoniazid depletes pyridoxine, impairing zinc-dependent enzymatic cascades. Rifampicin induces CYP3A4 via PXR activation, accelerating retinol catabolism and functionally coupling zinc deficiency to vitamin A insufficiency through impaired retinol-binding protein synthesis. The zinc–vitamin A axis demonstrates a strong positive correlation (r = 0.86, p < 0.01) in TB cohorts. Zinc supplementation (50 mg elemental zinc/day) improved sputum conversion rates and reduced hepatotoxicity markers in three randomized trials.Conclusions: Anti-TB drugs collectively create a “multi-hit” zinc depletion syndrome that extends beyond simple ethambutol chelation. We propose a clinical algorithm for baseline zinc assessment, risk stratification, and prophylactic supplementation during TB therapy. Persistent visual loss despite ethambutol discontinuation should prompt evaluation of concurrent zinc depletion from isoniazid, rifampicin, and the underlying TB disease itself.

Abstract: Rice (Oryza sativa L.) is an important staple crop in Mozambique, and understanding its genetic diversity is essential for crop improvement, genetic resources management and conservation. However, molecular characterization of Mozambican rice germplasm remains limited. This study assessed genetic diversity and population structure of 40 lowland rainfed rice genotypes using 3473 high-quality single nucleotide polymorphism (SNP) markers generated through DArTseq™ genotyping-by-sequencing platform. Results revealed moderate genetic diversity with a mean polymorphism information content of 0.25, indicating moderate marker informativeness. Unbiased expected heterozygosity (uHe = 0.314) was higher than observed heterozygosity (Ho = 0.125), reflecting the inbreeding nature of rice (FIS = 0.357). Model-based admixture analysis identified four subpopulations, with 20% of genotypes classified as admixed. Substantial genetic differentiation was observed among these subpopulations (FST = 0.267), which was broadly consistent with the principal coordinate analysis and the neighbor-joining tree. Furthermore, a high mean Manhattan dissimilarity index (0.70), indicated strong genetic divergence across the panel. Analysis of molecular variance revealed significant variation among subpopulations (32.90%) and within subpopulations (67.10%). These findings provide foundational genetic insights to guide Mozambican rice breeding programs and support the long-term conservation of local germplasm.

Abstract: Cancer remains a leading cause of death worldwide, with breast, lung, colorectal, prostate, and cervical cancers contributing significantly to global cancer-related morbidity and mortality. While individual lethality varies among these cancers, their combined impact on public health is substantial due to high incidence and, in some cases, limited access to early detection and effective treatment. These malignancies arise from a complex interplay of genetic, hormonal, lifestyle, and infectious factors, with molecular mechanisms that inform targeted therapies and precision medicine approaches. Advances in screening, immunotherapy, AI-assisted diagnostics, and minimally invasive surgical techniques have improved outcomes; however, challenges such as late diagnosis, treatment resistance, and healthcare disparities persist, particularly in low- and middle-income countries. This review provides a comprehensive synthesis of the epidemiology, risk factors, molecular pathogenesis, clinical features, current treatment strategies, emerging technologies, public health implications, and future research directions for the five deadliest cancers. Emphasis is placed on preventive measures, early detection, and equitable access to care, highlighting strategies to reduce the global cancer burden and improve survival outcomes.

Abstract: Background/Objectives: COVID-19 vaccine resistance was detrimental to herd immunity and worsened COVID-19 morbidity and mortality during outbreaks. Despite more evidence showing reactionary behavior among residents exposed to vaccine mandates, little research has been conducted on the effects of state proof-of-vaccine (POV) mandate bans in the United States (US). We sought to investigate the causal effects of POV mandate bans, overall and stratified by policy passage via executive order or state legislature, on 1st-dose COVID-19 vaccinations. Methods: In the contiguous US, 21 states enacted POV mandate bans from 2/8/2021–10/25/2021. Using a geographic regression discontinuity design, we selected treatment and control counties within 150 miles of the POV mandate ban state border. The resulting sample was 4,612 county-observations and 2,466 unique counties. We conducted two-way fixed effects estimation to compare changes in bimonthly, 1st-dose COVID-19 vaccinations among individuals under 65 years old before and after POV mandate ban enactment between treatment and control counties. Results: Among executive order POV mandate ban counties, we saw a reduction in the decreasing 1st-dose COVID-19 trend following POV mandate ban enactment. This corresponded to an additional 32.6% increase in 1st-dose COVID-19 vaccinations in Weeks 1–2, 34.5% in Weeks 3–4, 35.0% in Weeks 5–6, and 36.9% in Weeks 7–8 post-POV mandate ban enactment when compared to control counties. Conclusions: These findings suggest that executive order POV mandate bans reversed reactance to vaccine mandates. Future public health efforts should consider potential reactance to mandatory policies and tailor efforts to community values.

Abstract: China is committed to building a new development paradigm to realize Chinese modernization. Therefore, it is of great significance to delve into, from the standpoint of new quality productive forces (NQPF), how digital finance affects foreign investment. This study utilizes data from 31 Chinese provinces from 2011 to 2023 to ascertain the impact of digital finance on foreign investment. The findings indicate that digital finance exerts a significant and positive effect on foreign investment, with this effect being stronger in the central and western regions. With regard to transmission mechanism, digital finance can enhance foreign investment by improving regional NQPF, which has significant characteristics of regional heterogeneity. Further research makes a discovery that the outward foreign investment’s level in the central and western regions, is positively associated with the strength of digital finance’s effect on foreign investment, while the outward foreign investment’s level in the eastern regions, is negatively associated with the strength of digital finance’s effect on foreign investment. This research provides evidence for deepening digital finance’s development to promote foreign investment.

Abstract: The advent of CRISPR-based genome editing has transformed the conceptual framework of oncology—from descriptive molecular profiling to functional genome engineering. By enabling precise, programmable, and multiplex control of cancer-associated genes, CRISPR/Cas systems are reshaping how we model tumorigenesis, predict drug response, and design patient-tailored interventions. This Perspective discusses how CRISPR technologies are redefining precision oncology, the biological and ethical challenges that impede their clinical translation, and emerging strategies that integrate gene editing with immunotherapy, synthetic biology, and systems medicine. We argue that the future of cancer therapy lies not merely in editing genes but in orchestrating the dynamic networks that sustain malignancy.

Abstract: Non-Saccharomyces yeasts (NSY) are increasingly investigated as biotechnological tools to diversify wine profiles and modulate fermentation outcomes. This study evaluated the enological behavior of two Chilean isolates, Starmerella bacillaris (SB) and Hanseniaspora uvarum (HU), in Sauvignon Blanc must from the Casablanca Valley under monoculture and sequential inoculation (NSY → Saccharomyces cerevisiae) at laboratory (500 mL) and microvinification (10 L) scales. In synthetic medium (150 g/L sugars), SB and HU showed incomplete sugar consumption, producing 4.25% and 8.50% v/v ethanol, respectively, compared with 9.16% v/v for S. cerevisiae. In laboratory-scale fermentation in real must, both strains completed fermentation in monoculture, with moderate reductions in ethanol production relative to the control. At the microvinification scale, monocultures yielded lower ethanol concentrations (11.90–12.50% v/v) than S. cerevisiae (13.50% v/v), whereas sequential fermentations converged toward control values. NSY treatments showed higher relative abundances of medium-chain ethyl esters associated with fruity and floral sensory attributes while maintaining acetic acid concentrations ≤0.50 g/L. These findings indicate that the effects of SB and HU depended primarily on fermentation strategy and process scale under the evaluated conditions.

Abstract: Temperature control during hot-mix asphalt production and paving is critical to construction quality and emissions. However, conventional thermometry is susceptible to dust and vibration. This study proposes an indirect temperature monitoring system using electronic nose technology, exploiting the nonlinear correlation between asphalt VOC odor fingerprints and temperature. The system integrates a MOS sensor array with IoT feedback, with a proof-of-concept study involving three asphalt types at five temperature levels. Leave-One-Out Cross-Validation (LOOCV) was employed to mitigate overfitting. The hybrid modeling framework significantly outperformed the Multiple Linear Regression (MLR) baseline, achieving 88.9% three-class accuracy and a regression RMSE of ±6.2℃. Drift compensation improved accuracy by 16.4%. These results show the feasibility of multi-dimensional odor patterns for quantitative temperature prediction, offering a new paradigm for closed-loop, non-contact temperature control in smart, low-carbon pavement engineering.

Abstract: Effervescent tablets are highly hygroscopic solid dosage forms in which even minor surface defects can compromise product stability, dose uniformity, and patient safety. Reliable, high-throughput defect detection is therefore essential, yet the existing literature overwhelmingly focuses on compressed or film-coated tablets and rarely offers a systematic comparison across recent YOLO families and scales. This study presents a multi-scale performance benchmarking of three recent YOLO families—YOLO11, YOLO12, and YOLO26—on a newly constructed effervescent tablet defect dataset. The dataset comprises 251 high-resolution images acquired under controlled illumination, each containing 12 tablets, and is manually annotated in YOLO format across six physical-condition classes (intact, damaged, cracked, broken, moist, and stained), yielding 3,012 bounding-box instances. All five standard scale variants (n, s, m, l, x) of each family were trained for 100 epochs under identical hyper-parameter settings, producing fifteen model variants that are compared in terms of mAP@0.5, mAP@0.5:0.95, precision, recall, inference speed (FPS), parameter count, and FLOPs. Experimental results show that YOLO11l achieves the best overall accuracy, with 96.8% mAP@0.5 and 91.7% mAP@0.5:0.95, while YOLO11n offers the most attractive real-time trade-off at 345.9 FPS with 95.6% mAP@0.5 and only 2.5M parameters. YOLO12 variants deliver competitive accuracy but at markedly lower inference speeds for the larger scales, whereas YOLO26 scales lag in the nano regime (88.0% mAP@0.5) but close the gap at l/x scales. Class-wise analysis of YOLO11l shows consistently high performance across all six defect categories, with mAP@0.5 ranging from 0.940 (damaged) to 0.994 (stained). The results provide practical guidance for selecting a YOLO configuration for real-time effervescent tablet inspection lines and demonstrate that modern nano- and small-scale detectors are already sufficient for high-throughput pharmaceutical quality control.

Abstract: Background: Single cell proteins (SCPs) have significantly high protein content, contain low fat and are rich in various vitamins. They are produced from microbial fermentation of low-cost raw materials, some of which are considered as waste resources. SCP production has a reduced environmental footprint compared to con-ventional methods of producing protein. It also provides a way of converting waste products, including those containing hemicellulose into useful biomass. Objective: This review is focused on the current sustainability problem associated with the present food sys-tem alongside the global demand for protein which places a stress on it. The role of SCPs, a sustainable source of protein able to meet human nutritional needs is also considered. Method: We searched databases for primary and secondary research published on SCPs, Anthropocene, and Sustainability. Relevant articles were thereafter. Results: The food system is in the intersection of several overarching Sustainable Development Goals, and hence influences almost all planetary health boundaries. Contrary to processes associated with obtaining protein-rich foods from various animals, SCPs production is eco-friendly, offers an avenue for waste transformation, and does not impact the biogeochemical flow negatively. Nutritional contents of SCPs are good building blocks for the human immune system. Conclusion: Current challenges associated with SCPs mass production and consumption, especially eth-ic-related and downstream processing and purification technology and technical know-how can be overcome through an interdisciplinary research approach. The role of science communication in portraying SCPs as a safe microbial source of protein before the non-scientific communities cannot be overemphasized.

Abstract: The paper seeks to determine whether renewable energy is a future pathway for society or rather a temporary stage leading towards sustainable sources of energy. It evaluates the factors that affect the use of renewable energy in Malaysia through modeling their long-term relationship and short-term causalities. Time series data collected from 1970 to 2020 is used in the Johansen cointegration test and Vector Error Correction Model (VECM) to determine the association among renewable energy consumption, per capita GDP, foreign direct investments (FDI), carbon dioxide (CO2) emissions, oil prices, trade openness, and urbanization. There is evidence of a strong positive long-term association between renewable energy consumption and per capita GDP. However, there is evidence of a negative long-term relationship between renewable energy and FDI, CO2 emissions, oil prices, and urbanization. There is a positive relationship between renewable energy consumption and trade openness in the long term. In addition, short-term causality analysis shows the existence of a feedback loop between renewable energy consumption, economic growth, and FDI. Overall, the paper provides empirical evidence for the carbon-neutral target set by Malaysia in 2050.

Abstract: The tumor microenvironment (TME) is a highly adaptive and heterogeneous niche in which cancer stem cells (CSCs) promote immune evasion, metastatic dissemination, and therapy resistance. Among the mechanisms that support this phenotype, mitochondrial hijacking has emerged as a central strategy through which CSCs reprogram immune and stromal cells to favor tumor progression. This review synthesizes current evidence on how CSCs exploit mitochondrial transfer, particularly via tunneling nanotubes (TNTs) and extracellular vesicles (EVs), to impair antitumor immunity and remodel the metastatic niche. CSCs display marked metabolic plasticity, shifting between glycolysis and oxidative phosphorylation (OXPHOS) in response to environmental stress. They exploit this adaptability by transferring mitochondria and mitochondrial components to recipient cells, including tumor-associated macrophages (TAMs) and cytotoxic T cells, thereby disrupting ATP production, increasing oxidative stress, and skewing immune polarization. This mitochondrial hijacking contributes to an immunosuppressive milieu, stabilizes HIF-1α, and enhances PD-L1 expression, ultimately weakening T-cell activity and reinforcing CSC survival. EVs add another layer of regulation by transporting bioactive cargo, including oncogenic microRNAs (miRNAs) and mitomiRs such as miR-21, miR-210, and miR-34a. These molecules modulate mitochondrial gene expression, reshape immune signaling, and reinforce CSC phenotypes through autocrine and paracrine loops. Single-cell and spatial transcriptomic approaches have further revealed metabolic heterogeneity within CSC–immune synapses, identifying “metabolic hotspots” associated with profound immune dysfunction. Therapeutic strategies targeting OXPHOS, EV biogenesis, and miRNA activity are therefore being explored. In parallel, mitochondria-associated proteins such as TSGA10 may also contribute to CSC-driven immunometabolism regulation and deserve further investigation. Targeting downstream heterogeneity is like cutting the branches of a weed. Targeting the upstream mechanisms of mitochondrial hijacking and miRNA crosstalk aims to destroy the root (CSC plasticity) that generates the heterogeneity and drives therapy resistance in the first place. This review highlights mitochondrial hijacking and miRNA-mediated reprogramming as central determinants of CSC-driven immune escape and proposes a framework for precision interventions targeting CSC–immune interactions in metastatic cancer.

Abstract: Background/Objectives: Intermittent fasting (IF) has been widely investigated for its metabolic effects, including improvements in insulin sensitivity, lipid metabolism, and inflammatory markers. However, its psychological and experiential dimensions remain comparatively underexplored. The present narrative review examines IF within a psychobiological framework, integrating evidence from metabolic science, neuroendocrinology, and affective neuroscience to explore its potential impact on emotional regulation and interoceptive processes. Methods: A structured narrative literature search was conducted across PubMed, Scopus, and Google Scholar, focusing on studies published between 2000 and 2025. Eligible studies included human and relevant animal research addressing metabolic, hormonal, interoceptive, and psychological responses to IF. Evidence was synthesized thematically to identify convergent mechanisms linking metabolic adaptations to emotional and regulatory outcomes. Results: The available literature indicates that IF induces a metabolic shift toward lipid utilization, characterized by increased lipolysis, elevated circulating free fatty acids, and enhanced ketone body production, particularly β-hydroxybutyrate. These metabolic changes are accompanied by modulation of neuroendocrine pathways, including transient activation followed by adaptive recalibration of the hypothalamic–pituitary–adrenal axis, as well as alterations in insulin, leptin, and ghrelin signaling. Emerging evidence suggests that these physiological adaptations may influence central nervous system functioning through mechanisms involving neuroinflammation, mitochondrial efficiency, and synaptic plasticity. At the psychological level, IF appears to modulate interoceptive signaling, with heterogeneous emotional outcomes: structured fasting protocols have been associated with modest improvements in depressive symptoms and perceived stress in metabolically healthy individuals, whereas increased irritability, anxiety, or behavioral rigidity may occur in the presence of psychological vulnerability. Individual variability appears to be associated with differences in interoceptive sensitivity, stress reactivity, and traits related to anxiety, perfectionism, and eating-related pathology. Conclusions: Overall, IF may be conceptualized as a context-dependent psychobiological stressor whose effects extend beyond metabolic regulation to include interoceptive and emotional processes. These effects appear bidirectional, potentially promoting psychological resilience in some individuals while increasing the risk of affective destabilization or maladaptive behaviors in others. Current evidence remains limited by a lack of integrative and longitudinal studies combining metabolic and psychological measures. Future research adopting multidisciplinary approaches is needed to clarify the mechanisms underlying individual variability and to better define the potential benefits and risks of IF in both clinical and non-clinical populations.