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    • Article
    • Open Access

    Background/Objectives: Longitudinal dental examinations provide prognostic outcomes but are costly to collect. We investigated whether representations learned from public cross-sectional examinations could support prediction of new caries experience in baseline-sound permanent first molars when longitudinal labels are limited. Methods: An encoder learned masked tooth-state reconstruction from 5837 US National Health and Nutrition Examination Survey examinations. Among 919 baseline-eligible Saudi schoolchildren, 849 had complete eligible-tooth follow-up, with 263 events across 16 schools; frozen representations were evaluated for approximately one-year new caries experience. Nested internal–external evaluation across schools compared 15 prediction pipelines and representation controls, using development-only calibration and matched training-school budgets. Discrimination, probability accuracy, follow-up allocation, incomplete charts and outcome uncertainty were assessed. Results: Frozen transfer achieved an area under the receiver-operating-characteristic curve (AUROC) of 0.6848 versus 0.6643 for random forest, with Brier scores of 0.19461 and 0.19868; paired difference intervals included zero. At nominal 20% school capacity, 164 children were selected (19.32% realised capacity), capturing 89 versus 82 observed future cases: a difference of 2.66 percentage points (95% interval 0.31–5.86), conditional on fitted predictions. Exploratory training with eight of 15 development schools yielded AUROCs of 0.6663 and 0.6280, respectively. Allocation captured only four of 75 events among children aged 5–7. Conclusions: Transferred information may support limited-label prognosis, but clinically meaningful incremental value remains unconfirmed and selection coverage varies by age. Independent longitudinal validation and clinical-impact evaluation are needed before preventive-care deployment.

    Children

    12 November 2026

    • Article
    • Open Access

    Pre-Launch Assessment of Simulated CHIME and LSTM Data for Water-Quality Monitoring in a Virtual Constellation Framework

    • José Andrés Vargas-Solano,
    • Valentina Santarsiero and
    • Elisabetta Lamboglia
    • + 6 authors

    The use of Earth Observation data for monitoring of aquatic and coastal ecosystems has expanded significantly, yet gaps remain in the spectral and thermal capabilities needed to detect and characterize liquid discharges. This study evaluates the potential of simulated pre-launch CHIME and LSTM observations, integrated with operational Sentinel-2 and Landsat 8/9 data, for water-quality anomaly detection across diverse aquatic environments, demonstrating that the simulated datasets are sufficiently realistic to reproduce key water-quality and thermal indicators and support pre-operational application development prior to mission launch. A multi-stage workflow was applied: initial anomaly detection with multispectral imagery, thermal verification using LSTM-simulated brightness temperatures processed via linear and quadratic split-window algorithms, and spectral characterization of turbidity and spectral signatures with atmospherically corrected CHIME-simulated data. Results showed consistent spatial patterns of turbidity and surface temperature between simulated and operational products, with CHIME resolving finer spectral features of suspended matter and the quadratic LSTM model achieving low RMSE relative to Landsat thermal references. These findings demonstrate the cross-sensor consistency and complementary information provided by simulated CHIME and LSTM products, supporting their use in the pre-launch development of future multisensor workflows for detecting and characterizing optical and thermal water anomalies. Identification of specific contaminants and attribution of anomalies to individual discharge sources were not assessed in this study.

    Remote Sens.

    12 November 2026

    • Perspective
    • Open Access

    Neuromotor exercise is recognized as a distinct domain of physical fitness, yet operational criteria for classifying the neuromotor demands of individual exercises and systematically structuring their progression remain limited. The aim of this paper is to introduce the Neuromotor Exercise Progression (NEP), a quantitative conceptual framework for the classification and progression of neuromotor exercises in musculoskeletal rehabilitation, fitness, and sport settings. Building on the conceptual principles underlying Gentile’s taxonomy and guided by the American College of Sports Medicine conceptualization of neuromotor exercise, the NEP characterizes each exercise according to four variables: level of balance challenge, level of destabilization, degree of coordination, and level of locomotion. Balance challenge reflects the demands imposed by posture, stance, and base of support, whereas destabilization is intended to reflect proprioceptive demands associated with unstable support surfaces and other perturbations to postural and joint stability. Each variable is operationalized at three levels of increasing neuromotor demand. Exercises are classified according to the number of neuromotor components simultaneously challenged and an overall score derived from the four variables. Progression is primarily achieved by integrating a greater number of neuromotor components and secondarily by increasing the overall score within each level. The NEP is intended to provide a systematic basis for identifying the neuromotor profile of an exercise and for selecting and progressing exercises according to individual needs and functional goals. As a conceptual proposal, the framework requires further validation.

    • Review
    • Open Access

    Coordinating water allocation, pump scheduling, and hydraulic operation is essential for the safe and economical management of pumped water supply and transfer systems. Differences in planning horizons, hydraulic representations, and computational requirements complicate the translation of allocation plans into feasible equipment actions. This critical narrative review synthesizes multi-timescale coordination, economic–hydraulic coupling, and computational reduction methods and compares their applicability across system types and operating conditions. The synthesis identifies delivery windows, storage constraints, and operational feedback as essential links between decision layers. It distinguishes electricity cost savings from energy savings and shows why equipment transitions must be assessed alongside scheduled operating states. Hierarchical decomposition, model reduction, and surrogate models can offer computational benefits while requiring explicit feasibility checks and separate accounting of offline preparation and online decision time. Based on this synthesis, the review proposes a three-layer reference architecture linking water allocation, economic scheduling, and hydraulic execution through defined information exchanges, action-specific acceptance rules, and qualified fallback procedures. Future research should strengthen validation across time scales, uncertainty-aware hydraulic checking, and evaluation of computational performance under engineering operating conditions.

    Appl. Sci.

    12 November 2026

    • Article
    • Open Access

    Chronic inflammation within the prostate tumor microenvironment drives disease progression, in part because locally released cytokines make malignant cells more motile and better able to invade surrounding tissue. Plant-derived bioactive compounds may offer a potential strategy for attenuating inflammation-associated tumor aggressiveness. This study investigated the effects of the ethyl acetate fraction of Terminalia chebula Retz. (TC-EA) and its major constituent, chebulagic acid, on inflammation-stimulated migration and the invasion of castration-resistant prostate cancer (CRPC) cells. TC-EA was obtained by solvent-partitioning and chemically characterized using the Folin–Ciocalteu method and high-performance liquid chromatography. DU145 and PC3 cells were pretreated with TC-EA or chebulagic acid and subsequently exposed to conditioned medium derived from LPS-exposed THP-1 M1-like macrophages (M1-THP-1-CM), which contained elevated levels of IL-6 and IL-1β. Cell migration and invasion were assessed using wound-healing and Transwell invasion assays, respectively, while gelatin zymography, RT-qPCR, and Western blotting were used to evaluate invasion-associated molecular changes. TC-EA contained 511.12 ± 33.02 mg GAE/g extract of total phenolics and 264.34 ± 13.26 mg/g extract of chebulagic acid. M1-THP-1-CM significantly enhanced the migration and invasion in both cell lines, whereas neutralization of IL-6 or IL-1β attenuated these effects. TC-EA (10–40 μg/mL) and chebulagic acid (5–20 µM) significantly reduced M1-THP-1-CM-enhanced migration and invasion (p < 0.05). These effects were associated with reduced MMP-2 and MMP-9 activities, decreased expression of the invasion-associated proteins uPA, uPAR, and MT1-MMP, increased E-cadherin expression, and decreased N-cadherin and MT1-MMP mRNA expression (p < 0.01), and attenuated phosphorylation of AKT and GSK3β. These findings suggest that TC-EA and chebulagic acid may attenuate inflammation-driven migration and invasion of CRPC cells, potentially involving modulation of cytokine-associated AKT/GSK3β signaling.

    Int. J. Mol. Sci.

    12 November 2026

    • Article
    • Open Access

    Practical fixed-time backstepping control of uncertain electro-hydraulic position servo systems must address derivative-related terms induced by low-order nonsmooth virtual controls while ensuring a settling-time bound independent of the initial conditions. This paper proposes a practical fixed-time backstepping control scheme with an extended lumped disturbance observer for systems driven by three-stage electro-hydraulic servo valves. Based on a third-order strict-feedback model, system uncertainties and these derivative-related terms are incorporated into extended lumped disturbances in the mechanical and hydraulic channels. Fixed-time disturbance observers estimate these terms online, and the backstepping controller compensates for them to achieve trajectory tracking. Lyapunov analysis shows practical fixed-time stability of the closed-loop error system: all error states converge to a small neighborhood of the origin within a settling-time bound independent of the initial conditions, while all closed-loop signals remain bounded. Simulations demonstrate improved sinusoidal tracking accuracy and illustrate the practical fixed-time convergence behavior under different initial conditions. Experiments under sinusoidal and random-wave references demonstrate improved tracking accuracy with smooth servo-valve driving voltages.

    Actuators

    12 November 2026

    • Review
    • Open Access

    Cancer is increasingly understood as a tissue- and system-level disease shaped by dynamic interactions among malignant cells, stromal elements, the vasculature, the immune system, and the nervous system. In this context, tumors are not passive recipients of neural input, but active participants in the recruitment, remodeling, and exploitation of neural circuits that support tumor initiation, progression, metastasis, immune evasion, and resistance to therapy. Emerging work in cancer neuroscience has therefore shifted the field from a neuron-centric perspective toward an integrated model of the tumor microenvironment in which malignant cells help establish pathogenic neural niches. This review adopts a tumor-centric perspective to examine how cancer cells drive neoneurogenesis, engage in perineural invasion, and co-opt neural signaling and neuro-immune crosstalk to promote disease progression. It first distinguishes tumor-induced nerve growth and remodeling from perineural invasion as related but mechanistically distinct processes, then considers how tumor cell plasticity and neural mimicry enable malignant cells to acquire neuronal-like traits and exploit neural pathways. The review further explores how tumor-driven innervation shapes angiogenesis, immune modulation, therapeutic resistance, and minimal residual disease while also assessing emerging strategies designed to therapeutically target the tumor–nerve axis. By integrating these themes, the review highlights innervation not as a secondary feature of cancer, but as an active and potentially actionable dimension of tumor biology.

    Cells

    12 November 2026

    • Article
    • Open Access

    Biochar can improve composting, yet the ecotoxicological consequences of returning compost’s biochar to composting are poorly understood. Mature but off-specification compost was pyrolysed at 550 °C, and the resulting biochar (CBC) was added at 0, 3, 6 and 9% of dry matter to pilot-scale piles (one ~15 Mg pile per rate) of green waste and sewage sludge (9:1). After 39 days, the composts were analysed for respiration activity (AT4), nutrients, heavy metals and water-extractable ions and tested with the Phytotoxkit (Triticum aestivum, Sinapis alba, Pisum sativum) and Ostracodtoxkit (Heterocypris incongruens). CBC tended to increase K, Mn and Cu and reduce Ca and Mg; total metals remained below regulatory limits. CBC9 had the lowest AT4 (<10 mg O2 g−1), interpreted as inhibited microbial activity, and the strongest biological response (72.5% shoot inhibition in wheat; 83.2% ostracod growth inhibition). In PCA, these responses aligned with K, Mn, pH and oxidised N forms, probably markers of biochar loading. In this exploratory study, 3% CBC showed the most favourable ecotoxicological profile, though not an established optimum for compost quality; composts meeting chemical and stability criteria may still be ecotoxic.

    Molecules

    12 November 2026

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Highly Accessed Articles

  • Article
  • Open Access

I argue that the emerging sciences of synthetic morphology and diverse intelligence suggest non-physicalist models of mind and show how they can be empirically investigated. Whence the anatomical, physiological, molecular-biological, and behavioral properties of engineered new beings that have never before existed, and do not have a history of selection? Understanding, predicting, and guiding new forms of life and mind requires characterizing a structured latent space of patterns. Developmental, synthetic, and behavioral biology should take seriously, and exploit, the kinds of non-physicalist ideas that are already a staple of Platonist mathematics. I propose the following hypotheses. (1) Patterns in this space span a highly variable degree of agency, comprising a spectrum ranging from static truths studied by mathematicians to active ones studied by behavioral scientists (i.e., some patterns on the same spectrum as mathematical truths are kinds of minds). (2) The relationship between mind and body is the same as the relationship between causally instructive mathematical facts and physics. (3) Living beings have no monopoly on the “free lunches” provided by the ingression of these patterns into the physical world. While traditional computationalist views of living and cognitive systems are insufficient, my framework erases artificial distinctions between organisms and machines, framing all physical constructs (natural or engineered) as being, to various degrees, in-formed by patterns from the latent space. I sketch a research program, already begun, inspired by these ideas. Such frameworks, while contradicting long-held assumptions of both mechanists and organicists, could have many implications for evolutionary biology, regenerative medicine, AI, and the ethics of synthbiosis with the forthcoming immense diversity of morally important beings.

Philosophies

9 September 2026

80,724 Views
Bodies and minds self-assemble from single cells as a process of alignment and autopoiesis. (A) Most complex biological forms begin as one cell—a fertilized oocyte, commonly thought to be well-described by the laws of physics and chemistry. (B) A gradual, slow process of developmental morphogenesis results in the final form of the organism, which may have complex structure and a mind which may not believe it is a “machine”. Our transformation from a chemical soup into an active embodied mind is continuous but heterogeneous: (C) while we commonly think of ourselves as a unified intelligence with a “centralized” brain, the fact is that even the pineal gland, of which there is only one in the brain, is made of cells (C′) and those cells in turn are made of myriad other active components (C″)—we are a collective intelligence at all scales. (D) The creation of an “individual” out of an excitable medium such as an embryonic blastoderm with hundreds of thousands of cells is a dynamic process that is not hardwired: scratches made in that blastoderm would result in independent self-organization in each island, resulting in multiple embryos forming. This reveals the potentiality for some non-pre-determined number of minds to arise out of the same substrate. Images in (A,B,D) courtesy of Jeremy Guay of Peregrine Creative, used previously in [29]. Image (B) used with permission from [30]. Image in (C′) courtesy of Jose Calvo, Science Photo Library. Image in (C″) courtesy of Evan Ingersoll and Gaël McGill. Image (D) used with permission from [31].
  • Review
  • Open Access

Background: Chlorine dioxide (ClO2), formulated as an aqueous solution (CDS), has been proposed as a therapeutic agent, yet its classification among oxidizing compounds is frequently confounded with chemically distinct species—sodium chlorite (NaClO2) and sodium hypochlorite (NaOCl). Objective: This study aimed to synthesize the physicochemical, mechanistic and cellular basis of ClO2 action and to delineate the distinctions between ClO2 and related oxidants, with explicit separation of established data from hypothesized data. Methods: The methodology includes a narrative synthesis of electrochemical data, primary toxicological and clinical literature (PubMed) and the redox-biology literature on low-dose oxidant signaling. Results: ClO2 is a neutral free radical that acts via one-electron transfer (E°′ = +0.95 V vs. SHE for the half-reaction ClO2 + e− → ClO2−, essentially pH-independent over pH 4–8, pH-independent) without chlorination. Its antimicrobial action is attributable to oxidation of thiol-dependent enzymes and membrane constituents and to the inhibition of bacterial respiratory metabolism; host-cell sparing is consistent with differential glutathione-dependent buffering. Controlled human ingestion studies at low concentrations report a favorable short-term safety profile; conversely, the principal metabolite (chlorite) is associated with documented developmental toxicity in animals and regulatory caution by EPA/WHO. Low-dose ClO2 exposure is hypothesized—but not yet directly demonstrated—to elicit dose-dependent adaptive redox responses and redox-regulatory modulation. Conclusions: The one-electron, non-chlorinating chemistry of ClO2 provides a coherent mechanistic framework. The translation of this framework into clinical application requires prospective trials and direct mechanistic measurement, ideally conducted by independent investigators. The following mechanisms are hypothesized and have not yet been directly demonstrated in vivo: modulation of oxidative phosphorylation, mitochondrial oxygenation, and associated redox-regulatory signaling. Reported antimicrobial efficacy typically occurs in the low-ppm range (0.1–5 ppm), whereas adverse effects on mammalian cells in the reviewed literature are reported at concentrations at least one order of magnitude higher; direct head-to-head cytotoxicity comparisons remain scarce and are identified as a priority for future work. This differential thiol buffering—in particular, the higher glutathione content of many mammalian cells relative to many pathogens—has been proposed as a contributing basis for host-cell sparing; direct quantitative confirmation in vivo is not yet available. Bacterial species possess their own thiol-based defense systems (e.g., mycothiol in actinomycetes, bacillithiol in Firmicutes), and the interplay between ClO2 and these systems requires further investigation.

Biophysica

21 September 2026

15,926 Views
Mechanistic overview. ClO2 acts via one-electron oxidation of microbial targets (thiol oxidation, envelope and nucleic acid damage, respiratory inhibition); host cells are spared through glutathione-dependent redox buffering. The proposed low-dose hormetic response is a hypothesis requiring direct experimental confirmation, as discussed in Section 4.2.
  • Article
  • Open Access

Evidence of Selective Response in the Free-Breeding Dog Population in Chornobyl

  • Megan N. Dillon,
  • Reade B. Roberts and
  • Matthew Breen
  • + 3 authors

Background/Objectives: Understanding genomic responses to environmental contamination is essential for assessing long-term ecological and genetic risk. The free-breeding dogs inhabiting the Chornobyl Exclusion Zone (CEZ) offer a unique, multigenerational model for investigating these responses within a chronically contaminated landscape. Following the 1986 radioecological disaster at the Chornobyl Nuclear Power Plant, and subsequent remediation activities, the surrounding environment was contaminated by ionizing radiation, heavy metals, organic compounds, and other environmental toxicants. Our previous work identified significant genetic differentiation between two distinct but geographically proximate dog populations within the CEZ, a pattern not explained by breed composition, spatial isolation, or increased mutation rates. Methods: In this study, we tested the hypothesis that the dogs residing at the nuclear power plant show genomic signatures consistent with adaptive evolution in response to chronic environmental stressors. This work extends prior population-genetic analyses by integrating whole-genome selection scans with estimates of effective population size and comparative measures of population divergence, providing a framework to evaluate whether the observed genomic differentiation is more consistent with selection than demography. Using these whole genomic data, we evaluated chromosome-level FST metrics, estimated effective population size (Ne), and analyzed a geographically isolated island dog population as a comparative reference for genetic divergence. Results: We continued to find that the levels of genetic differentiation are not comparable to other free-breeding dog populations. Genome-wide outlier analyses identified candidate loci showing evidence of positive selection across multiple metrics. Conclusions: Genes associated with these loci were enriched for biological functions related to DNA replication and repair, cell death and survival, cellular compromise, immune response, and cancer-associated pathways, suggesting biologically plausible mechanisms through which chronic environmental stress could influence fitness. These findings are consistent with directional selection in the nuclear power plant population, which could potentially be associated with the environmental variables present, and advance our understanding of local adaptation and genomic resilience under chronic environmental contamination.

Genes

27 September 2026

8,858 Views
Historical effective population size (Ne) estimations generated through GONE analysis. The plot visualizes the Ne as estimated for the past 100 generations for each population, with points for the population size estimates and a loess smoother for these data points with default confidence band in gray. CC indicates Chornobyl City (in gold) and NPP indicates the Nuclear Power Plant population (in blue).
  • Review
  • Open Access

Neglected tropical diseases (NTDs) caused by Leishmania and Schistosoma species continue to impose a significant health burden in endemic regions, largely due to limited therapeutic options, drug resistance, and incomplete understanding of parasite biology at the molecular level. A major restriction in the development of targeted interventions is the structural inaccessibility of parasite membrane-associated proteins, which are central to host invasion, nutrient transport, immune evasion, and survival. Recent advances in cryogenic electron microscopy (cryo-EM) have expanded the structural biology toolkit available for studying difficult parasite proteins, particularly large and membrane-associated macromolecular assemblies. However, experimentally resolved cryo-EM structures remain limited for many of the Leishmania and Schistosoma targets relevant to therapeutic and vaccine development. This review therefore distinguishes experimentally determined structures from partial structural information and computational models and examines how potential cryo-EM approaches may address unresolved structural questions. We discuss current structural knowledge of selected parasite targets, approaches for recombinant expression and membrane-protein stabilization, membrane-mimetic systems for structural characterization, and computational methods that complement experimental structural biology. We further examine how experimentally supported structural information, complemented by computational predictions where appropriate, could contribute to structure-guided drug discovery, vaccine design, and targeted nanomedicine. At present, however, the direct translation of parasite structural information into rational nanotherapeutic design remains limited. Key gaps include the scarcity of experimentally resolved parasite membrane protein structures, challenges in their expression and structural characterization, and limited integration of structural biology with nanoparticle engineering. Resolving these gaps may improve the prospects for structure-informed therapeutic and nanomedicine applications against leishmaniasis, schistosomiasis, and other NTDs.

Curr. Issues Mol. Biol.

30 September 2026

8,239 Views
Molecular representation of experimentally characterized structural regions of selected Leishmania and Schistosoma targets (extracted from the PDB database and visualized with ChimeraX software). (A) X-ray crystal structure of Leishmania major leishmanolysin (GP63; PDB 1LML), showing the experimentally determined protein architecture and catalytic zinc-containing region. (B) Solution NMR structure of the extracellular EC2 domain of Schistosoma mansoni Sm-TSP-2 (PDB 2M7Z). The Sm-TSP-2 structure represents an 81-residue extracellular domain and does not resolve the complete four-pass membrane protein or its organization within the native tegument. The structures illustrate the different levels and experimental methods of structural evidence available for these parasite targets.

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Editor's Choice Articles

  • Review
  • Open Access

Genetic and Molecular Basis of Heat Stress Resilience in Pigs: Mechanisms, Genomic Regions, and Breeding Perspectives

  • Vasileios G. Papatsiros,
  • Georgios I. Papakonstantinou and
  • Georgios Michailidis
  • + 4 authors

Background/Objectives: Heat stress is one of the most economically and physiologically important constraints on pig (Sus scrofa domesticus) production, affecting welfare, reducing feed intake, growth, and reproductive efficiency, while increasing morbidity and mortality; because pigs lack functional eccrine sweat glands and have a limited capacity for evaporative heat dissipation, their ability to cope with high ambient temperature depends heavily on behavioral, physiological, and cellular stress-response mechanisms, which vary among individuals and genetic backgrounds. This review synthesizes current knowledge of the genetic and molecular pathways underlying the pig heat-stress response, spanning the HSF1–heat shock protein axis and epigenetic regulation, as well as genomic regions, candidate genes, nutrigenomic modulation, and reproductive consequences in boars and sows. Methods: A narrative literature review, informed by key principles of the PRISMA 2020 statement, synthesized 58 peer-reviewed transcriptomic, genomic, epigenomic, proteomic, and physiological studies published mainly between 1998 and 2026. Results: Heat exposure activates HSF1-driven heat shock protein transcription, oxidative stress, gut tight-junction disruption, hypothalamic–pituitary proteomic remodeling, and sex-dimorphic apoptotic/inflammatory transcriptional programs that also compromise boar semen quality. GWAS and QTL studies have mapped genomic regions and candidate genes for thermoregulatory, reproductive, and growth traits. At the same time, breed comparisons suggest, but do not prove on their own, a genetic contribution to the smaller physiological responses observed in some tropical and Mediterranean-adapted breeds. Heritability estimates for individual heat-stress-related traits, rather than for heat tolerance as a composite phenotype, range from low (0.02–0.20) for reproductive traits, to moderate (0.35–0.39) for thermoregulatory traits in lactating sows, to moderate-to-high (0.49–0.83) for physiological responses to acute heat challenge in gilts; circulating cortisol (h2 ≈ 0.68) is a heritable biomarker of the stress response rather than a measure of heat tolerance itself. Conclusions: Several traits associated with the response to heat stress in pigs are heritable and polygenic, supporting the potential of genomic selection, reaction-norm modeling, and marker-assisted introgression, although functional validation of candidate genes and larger multi-population studies, together with an explicit definition of heat tolerance as a composite selection objective, remain priorities.

DNA

5 November 2026

An integrative overview of the genetic and molecular pathways underlying heat-stress resilience in pigs. Environmental heat stress and an elevated temperature–humidity index (THI) impose anatomical and physiological constraints that trigger cellular and molecular stress responses, including heat-shock and oxidative, inflammatory, neuroendocrine, intestinal, and epigenetic pathways. These responses interact with genomic variation, candidate genes, and breed-specific adaptation to influence thermoregulatory, reproductive, growth, health, and welfare phenotypes. The resulting genetic and phenotypic information can support precision phenotyping, genomic selection, reaction-norm modeling, and complementary management and nutrigenomic strategies for improving heat resilience in pigs. The figure integrates direct porcine evidence with conserved mammalian mechanisms and proposed applications discussed throughout the review.
  • Review
  • Open Access

Somatic hematopoietic mutations, particularly clonal hematopoiesis of indeterminate potential (CHIP), represent an emerging link between aging, inflammation and cardiovascular disease beyond their established relevance in hematology. This narrative review examines how acquired mutations in hematopoietic stem and progenitor cells contribute to cardiovascular pathogenesis and how this knowledge may inform precision prevention and therapy. Evidence from experimental, clinical and population studies was synthesized with emphasis on clonal expansion, variant allele fraction, gene-specific mechanisms and cardiovascular phenotypes. The reviewed data indicate that driver mutations in DNMT3A, TET2, ASXL1, JAK2, TP53 and PPM1D can promote chronic myeloid inflammation, NLRP3/IL-1β and IL-6 signaling, endothelial dysfunction, atherosclerotic plaque instability, myocardial fibrosis, adverse remodeling, thrombosis, arrhythmias and cardio-oncology complications. The cardiovascular impact of CHIP appears heterogeneous and depends on the mutated gene, clone size, inflammatory phenotype, age, sex, treatment exposures and traditional risk factors. Anti-inflammatory, antithrombotic and mutation-oriented strategies, including IL-1β/NLRP3 blockade and pathway-specific approaches, are promising but remain incompletely validated. Somatic hematopoietic mutations should be considered cardiovascular risk modifiers rather than uniform disease entities. Future studies are needed to define screening thresholds, clinical utility and safety of CHIP-guided risk stratification and targeted therapy.

Cardiogenetics

3 November 2026

Clonal Expansion and Stepwise Mutation Accumulation in Hematopoietic Stem and Progenitor Cells. This figure illustrates the biological basis of clonal hematopoiesis, showing how acquired somatic mutations in hematopoietic stem and progenitor cells (HSPCs) can confer a selective advantage, leading to clonal expansion and altered myeloid cell function and inflammatory signaling. Clonal hematopoiesis of indeterminate potential (CHIP), particularly involving mutations in TET2 and ASXL1, has been associated with an increased risk of cardiovascular disease, including atherosclerosis, heart failure, arrhythmias, thrombosis, aortic stenosis, and myocardial remodeling. Experimental studies support potential mechanistic links between specific mutations, inflammation, endothelial dysfunction, and cardiovascular pathology. However, epidemiological associations do not establish causality, and causal relationships remain incompletely demonstrated in humans. Further accumulation of somatic mutations may also contribute to progression toward hematologic malignancy, although this process is not depicted explicitly in the figure. Abbreviations: HSPCs, hematopoietic stem and progenitor cells; CHIP, clonal hematopoiesis of indeterminate potential; IL, interleukin; TNF-α, tumor necrosis factor alpha; NLRP3, NLR family pyrin domain containing 3.
  • Article
  • Open Access

Electric Double Layers in Soils as Basis for Micro-Aggregation

  • Edgar Galicia-Andrés,
  • Chris Oostenbrink and
  • Martin Gerzabek
  • + 1 author

The behavior of ions at the electric double layer interfacial region between solid and liquid phases is well known in surface and material science. However, this is not fully the case in soil science, where the electric double layer develops due to the inherent complexity and diversity of negatively charged soil organic matter molecules that sorb at the mineral surface. This lack of knowledge opens questions regarding the interaction mechanisms at the molecular scale that lead to the stabilization of such soil building blocks, the so-called organo-mineral aggregates. By using classical molecular dynamics simulations, we studied the interactions between Kaolinite and four standardized soil organic matter samples with different aromatic and carboxylic content and Ca2+ cations clustering OM molecules and stabilizing them to the surface. We assessed the influence of (i) organic content, (ii) water content, and (iii) competing Cl− ions. Cluster aggregates are favored in soils with a high aliphatic fraction at low-water content, whereas aggregation is favored in soils with high aromatic fraction at high-water content and in the presence of Cl− ions. Moreover, samples with a low acid fraction favor clustering due to non-bonded interactions and hydrogen bonds. All of these environments are reflected as unique charge-density “fingerprints” and surface coverage for each OM sample. This work represents a step towards the characterization and study of natural soils tunable to specific local conditions.

Minerals

30 October 2026

Snapshot of cavities: (a) partially filled, (b) fully filled by water, and (c) fully filled by water and extra ions (CaCl2 solution). The cavity is represented by the periodic image of the Kaolinite basal surface in the z-direction. OM is represented by the green surface, Ca2+ ions by magenta spheres, and Cl− ions by yellow spheres.
  • Review
  • Open Access

Non-dilated left ventricular cardiomyopathy (NDLVC) presents a unique clinical paradox: patients with nearly identical phenotypes can face radically different clinical outcomes. NDLVC has been recently recognized as a distinct dynamic phenotype within the spectrum of non-ischemic cardiomyopathies, linked by a high risk of life-threatening arrhythmias. Recent advances in genetics have overcome clinical phenotyping in prognostic accuracy. Specifically, gene-specific scores have been introduced to guide primary prevention ICD in high-risk gene carriers. On the other hand, while gene-elusive cases present a more favourable arrhythmic profile, their long-term clinical outcome is more challenging to predict. Despite advancements in therapeutic strategies, the heterogeneity of the disease represents an ongoing dilemma for risk stratification and long-term surveillance. This review offers a comprehensive analysis of NDLVC management in clinical practice, highlighting the profound prognostic divergence between genetic (both in actionable and VUS carriers) and gene-elusive cohorts. By synthesizing current evidence, we aim to clarify how genotype–phenotype correlations influence clinical outcomes and to provide a framework for more personalized approaches in the follow-up and treatment of these distinct patient populations. Furthermore, we address the current lack of standardized guidelines specifically tailored to gene-elusive phenotypes. In conclusion, NDLVC management requires a paradigm shift towards a multi-parametric, genotype-directed framework, where cardiac magnetic resonance tissue characterisation and personalized risk scores are essential to optimize sudden cardiac death prevention. Future research must leverage artificial intelligence and polygenic risk scores (PRSs) to integrate multi-parametric clinical-imaging data and refine risk stratification beyond traditional binary models. Concurrently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) will be pivotal as a translational platform to clarify VUS pathogenicity, unravel gene-specific arrhythmic mechanisms, and accelerate targeted therapeutic interventions.

Cardiogenetics

30 October 2026

Methodological Workflow for VUS Management: From Multi-Parametric Evidence Streams to Clinical Decision-Making.