Browse Articles

Dynamic metacognitive regulation prospectively predicts reduced interpersonal epistemic invalidation: a three-wave random-intercept cross-lagged panel study

Abstract Interpersonal epistemic invalidation, often described within the broader gaslighting literature, has been linked to psychological distress, yet little is known about dynamic cognitive processes that may be associated with variation in reported exposure over time. Metacognitive awareness, defined as the capacity to monitor and regulate one’s own cognitive states, has been theorized to confer greater epistemic destabilization. However, prior research has relied primarily on cross-sectional designs, precluding separation of stable individual differences from dynamic within-person change. In a three-wave longitudinal study of 300 adult women residing within arranged or family-structured marital contexts assessed across a 10-week interval, we applied a random-intercept cross-lagged panel model (RI-CLPM) to disentangle trait-level associations from intra-individual temporal dynamics. Metacognitive awareness and gaslighting exposure were measured at each wave, alongside a multimethod behavioral subsample ( n  = 30). The invalidation measure assessed subjective interpersonal experiences without specifying source context. Longitudinal measurement invariance was established prior to structural modeling. At the between-person level, women with chronically higher metacognitive awareness reported lower overall endorsement of interpersonal epistemic invalidation experiences. Critically, at the within-person level, increases in metacognitive awareness above an individual’s typical baseline were prospectively associated with subsequent decreases in self-reported gaslighting exposure across both lag intervals, whereas reverse pathways were nonsignificant. Component-level analyses indicated that conditional knowledge and information management processes showed independent prospective associations with subsequent reported gaslighting exposure. In the behavioral subsample, observational indicators showed increases in reflective questioning and decreases in confusion and withdrawal across time. These findings are consistent with the interpretation that metacognitive awareness may function as a dynamically enacted regulatory process associated with subsequent changes in reported gaslighting exposure. By separating stable traits from short-term fluctuations, the present study contributes to understanding of cognitive processes that may be relevant to resilience in contexts involving sustained interpersonal invalidation and epistemic challenge.

Why environmental scientists need ethics training more than ever before

Chitosan/β-cyclodextrin nanocarriers enhance 5-fluorouracil efficacy against colorectal cancer via pH-responsive release and apoptosis modulation

Abstract Globally, colorectal cancer continues to be a major cause of cancer-related death. Clinical application of 5‑fluorouracil (5‑FU) is constrained by reduced bioavailability and dose‑limiting toxicity. To overcome these restrictions, a ternary drug delivery system was developed in this study. Chitosan and β‑cyclodextrin were physically assembled into a pseudopolyrotaxane complex, and 5‑FU was incorporated by solvent evaporation to form a solid dispersion. The resulting nanocomposite had a mean hydrodynamic diameter of 187 nm and a zeta potential of + 32.5 mV. Fourier transform infrared spectroscopy revealed peak shifts consistent with non‑covalent interactions. X‑ray diffraction confirmed amorphization of 5‑FU within the formulation. The ternary system released 5‑FU more rapidly at pH 5.5 than at pH 7.4. In HCT‑116 colorectal cancer cells, the 5‑FU/chitosan/β‑cyclodextrin formulation showed an IC 50 of 16.5 µM, compared with 42.5 µM for free 5‑FU and 27.5 µM for the binary 5‑FU/β‑cyclodextrin complex. Gene expression analysis indicated upregulation of P53 and Caspase‑3 and downregulation of BCL2 and VEGF . A complementary in silico analysis of 5-FU-responsive genes (from public dataset GSE183977) identified a protein‑protein interaction network enriched in apoptosis and cell‑cycle pathways, with IL6 , MYC , EGR1 , and ATF3 as central hub genes. The obtained results show that incorporation of 5‑FU into a chitosan/β‑cyclodextrin matrix improves its activity against colorectal cancer cells. This effect is attributed to enhanced solubility, pH‑responsive release, and modulation of apoptotic and angiogenic pathways.

Multistep electron tunneling through tryptophans in the KatG bifunctional peroxidase monitored by a nonperturbing spin probe

The bifunctional heme peroxidase from B. pseudomallei (BpKatG) utilizes heme and three tryptophans (Trp139, Trp153, and Trp330) as unique redox cofactors in the peroxidase-like catalytic cycle, as was shown previously by multifrequency Electron Paramagnetic Resonance (EPR) spectroscopy combined with isotope labeling and site-directed mutagenesis. In this work, we exploited the redox properties of a strategically attached nitroxide as a direct probe of the long-range multistep electron-tunneling pathway between Trp153 • and the high-valent heme intermediate, thereby showing it is mediated by Trp94 and Trp95. We also demonstrated that the equilibrium between the [Fe IV = O Trp153 • ] and [Fe IV = O Trp139 • ] intermediates, which is observed in the absence of substrate, is preferentially shifted toward catalytic oxidation of isoniazid substrate by Trp139 • . Our EPR experimental data confirm that Trp139 • oxidatively activates the isoniazid prodrug, in sharp contrast to the current view that [Fe IV = O Por •+ ] is the oxidant, as in canonical peroxidases.

Fishing and warming reshape size spectra of commercial species in the Mediterranean Sea

Spectroscopic elucidation of an electron-delocalized copper–tyrosine state in heme–copper oxidases reveals its role in proton pumping

Heme–copper oxidases, the terminal respiratory complex in the electron transport chain, harness the energy from the reduction of dioxygen to water to pump protons across mitochondrial or bacterial membranes against a gradient to power ATP synthesis. While proton pumping in heme–copper oxidases was discovered more than four decades ago, a molecular-level understanding of the proton pumping mechanism remains elusive. Particularly, the role of the heme–copper active site, including a unique tyrosine residue covalently crosslinked to a copper ligand, remained inaccessible due to intense overlapping spectroscopic features from other redox centers in these enzymes. Here, by leveraging site-selective spectroscopic methods, we show that the active site copper and its crosslinked tyrosine directly control the proton pumping, providing the molecular mechanism underlying this process. This was achieved by experimental elucidation of the key intermediate F, formed in the first proton pumping step in heme–copper oxidases. By performing variable-temperature, variable-field magnetic circular dichroism spectroscopy on the oxo-heme center and K-edge X-ray absorption spectroscopy on the copper center of F, we find that the iron(IV)-oxo in F is ferromagnetically coupled to an electron-delocalized copper/tyrosine radical. These results show that the copper(I)-tyrosyl radical character, triggered by protonation of the heme–copper center, enables proton pumping. Furthermore, we find that the copper-tyrosyl radical character is regenerated in all four proton pumping intermediates, completing the molecular mechanism for proton pumping by the respiratory oxidase family of enzymes.

Retraction Note: Cognitive salience features enhance multitask deep learning for pragmatic reasoning across cultures

A transcription factor modulates dermal architecture to generate structural and pigment color diversity in lizards

The way organisms perceive the world influences their evolution. Many animals detect ultraviolet (UV) light invisible to humans, creating sensory contexts that alter the selective landscape for coloration. Here, we dissected the molecular basis of a UV-reflecting color morph in common wall lizards, uncovering its association with a noncoding region upstream of the transcription factor PAX7 . Our results suggest that variation at this locus alters dermal architecture by modifying the cellular composition, exposing structures within specialized cells that generate UV structural coloration. We further demonstrate that the PAX7 locus acts epistatically on other color genes to suppress pigment deposition, revealing a genetic interaction between pigmentary and structural pathways that underlie color production. Across populations, the frequency of the UV morph was not predicted by environmental variation, arguing against climate-driven selection. Inferred frequencies of the UV-associated allele across sampled populations exhibited weaker spatial structure than expected from genome-wide variation, suggesting this polymorphism may be maintained by balancing selection. Our findings reveal mechanisms of phenotypic evolution beyond human perception and a genetic link between pigmentary and structural coloration.

Intelligent credit risk assessment for rural small and micro enterprises based on hybrid deep learning architecture

Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer. Loss of von Hippel–Lindau (VHL) and the consequent activation of hypoxia-inducible factor-α (HIFα, especially HIF2α) plays an essential role in ccRCC initiation and progression. The VHL–HIF2α axis as the main driver for ccRCC may present specific opportunities to control the disease by cotargeting HIF2α with belzutifan and another vulnerability. This study elucidates the synthetic essentiality of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) in VHL-deficient ccRCC. Upregulated in ccRCC in a VHL–HIF2α-dependent manner, TRAIL is selectively essential in ccRCC cells, promoting cell proliferation by activating the p38 MAPK pathway and facilitating G1/S phase transition. Depletion of endogenous TRAIL or inhibition of HIF2α with belzutifan sensitizes ccRCC cell and tumor models to recombinant TRAIL, presenting a promising avenue for combination therapy in ccRCC.

In-hospital detection of deep vein thrombosis after surgical treatment of open patellar fractures

Combinatorial decision-making driven by multicomponent surface condensates

Living organisms rely on molecular networks, such as gene circuits and signaling pathways, for information processing and robust decision-making in crowded, noisy environments. Recent advances show that interacting biomolecules self-organize by phase transitions into coexisting spatial compartments called condensates, often on cellular surfaces such as chromatin and membranes. In this paper, we demonstrate that multicomponent fluids can be designed to recruit distinct condensates to surfaces with differing compositions, performing a form of surface classification by condensation. We draw an analogy to multidimensional classification in machine learning and explore how hidden species, analogous to hidden nodes, expand the expressivity and capacity of these interacting ensembles to facilitate complex decision boundaries. By simply changing levels of individual species, we find that the same molecular repertoire can be reprogrammed to solve new tasks. Together, our findings suggest that the physical processes underlying biomolecular condensates can encode and drive adaptive information processing beyond compartmentalization.

A systematic trust management system for RPL based IoT networks using machine learning

Abstract As IoT networks continue to evolve, concerns about their security risks are growing. Several security gaps still exist within IoT systems like Blackhole, Decreased Rank, Version Number, and Flooding attacks. During these attacks the intruder cheat legitimate nodes. Hence, affecting trustworthiness. One potential solution is the Trust Management System (TMS). TMS evaluates the trustworthiness of nodes, offers real-time predictions, detects attacks and aids decision-making to offer secure routing. This work proposes a lightweight, reliable and dynamic TMS to enhance IoT network security. There are two primary challenges in developing an AI-driven security system for IoT. The first is the availability of IoT datasets that include trust-based attacks and trust value as labels. The second is the inherent uncertainty of trust, which complicates the development of a dynamic system. The proposed TMS relies on three novel set of trust indicators: network flows, recommendations, and social behaviour. These indicators are aggregated using a modified Beta Distribution function to represent trust as labels in the dataset. The work also discusses the design of a lightweight and real-time trustworthiness predictor based on Kernel Extreme Learning Machine (KELM), which uses the labels from Beta Distribution for more accurate and reliable predictions. Furthermore, a dynamic threshold evaluation module is introduced to classify the nodes as either trustworthy or untrustworthy based on distance metrics. The proposed TMS is validated against four types of trust-based attacks—Blackhole, Decreased Rank, Version Number, and Flooding—which have not been adequately addressed in existing literature. The performance of proposed model is also validated on binary and multiclassification. Comparisons existing linear and non-linear machine learning models demonstrate that the proposed system outperforms current state-of-the-art TMS solutions, achieving 99.95% accuracy, 99.9% precision, 99.96% recall, and a minimal misclassification rate of just 0.05%.

Neuropeptide signaling and the blood–brain barrier generate a persistent stress-induced internal state in <i>Drosophila</i>

Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety or phobia are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior (CLB) in Drosophila . Unlike aversive memory formation, the development of CLB does not require dopamine receptors. Our neuronal screening determined that neuropeptide signaling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing CLB. Moreover, gene expression profiling of individual fly heads revealed that innate immune response activation in the blood–brain barrier is involved in CLB. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signaling and the blood–brain barrier, providing the mechanism determining internal states which persistently change into a phobia-like mode.

Joule-Heated direct writing: an electrically-driven additive manufacturing paradigm for space fabrication

Dual salt bridges govern proton gating and calcium leak in <i>Bs</i> YetJ across bilayers and live cells

Proton-coupled ion transport is a fundamental chemical process underlying membrane physiology, yet how local electrostatics are transduced into gated Ca 2+ permeation remains poorly defined. Here, we combine single-channel planar bilayer electrophysiology, nanodisc-based double electron–electron resonance spectroscopy, atomistic modeling, and a nanodisc nano-delivery strategy that enables direct functional insertion of purified membrane proteins into live mammalian cells. Applying this integrated toolkit to the bacterial transmembrane Bax-inhibitor-1–containing motif prototype Bs YetJ, we resolve a hierarchical electrostatic gating mechanism governed by two salt bridges with distinct physical roles. A periplasmic E49–R205 interaction functions as a proton-sensitive latch that drives transmembrane helix 2 displacement and controls opening probability, while a cytoplasmic E182–R15 pair operates as a local electrostatic determinant of Ca 2+ self-block that tunes conductance and selectivity without large-scale conformational change. Quantitative separation of these effects reveals how protonation reshapes the energy landscape of ion permeation. Live-cell Ca 2+ imaging following nano-delivery recapitulates this gating logic in a cellular membrane setting. Together, this work establishes dual salt-bridge electrostatics as a chemical principle for graded Ca 2+ leak and introduces nano-delivery as a powerful platform for connecting molecular electrostatics to cellular ion transport.

Production of Fe metal from Fe ores through novel molten oxide electrolysis at 1173 K

Social and spatial affinity drive wound care in ants

In social animals, open wounds pose a risk not only for the injured individual but also for its wider social context, especially when the probability of infection transmission is high. To mitigate this danger, different strategies have evolved across species, with ants representing one of the few taxa beyond humans that engage in social wound care. Yet, who provides this care and what drives care provision remains unexplored. To answer these questions, we combined controlled injury experiments with automated behavioral tracking and simulations across six colonies of the ant Camponotus fellah . Our results demonstrate that caregivers are workers in a transitional state between nursing and foraging roles, characterized by elevated activity and broad nest coverage. Being in this transitional state, however, is required but not sufficient to explain the temporal dynamics of individual care provision. Instead, care provisioning is best explained by preinjury spatial overlap, encounter rates, and social interactions, which together constitute an affinity index that predicts both the frequency and duration of subsequent wound care events. We further show that the treatment of open wounds is not the result of a generalized increase in social behaviors directed to the injured ants but part of a care response toward injuries that also involves an increase in allogrooming. Taken together, our findings reveal the necessary conditions for an individual to act as a caregiver and highlight affinity-driven dyadic interactions as an underexplored mechanism for the behavioral coordination of social immunity strategies in decentralized caste-based insect societies.

Retrospective detail reconstruction network for mitigating shallow information loss in colorectal polyp segmentation

Abstract Existing medical polyp segmentation networks predominantly rely on hierarchical feature representations to improve boundary delineation. However, we identify a critical yet underexplored issue, termed shallow information loss, wherein low-level layers irreversibly suppress low-contrast but semantically essential edge cues during forward propagation, while attenuated gradients in backpropagation are insufficient to recover such early-stage information loss. This problem is especially severe in polyps exhibiting fractal-like structural characteristics, where cross-scale self-similarity is progressively disrupted across spatial resolutions, ultimately degrading segmentation performance. Moreover, most existing approaches attempt to learn a direct pixel-to-semantic mapping in a single step, lacking progressive feature guidance and resulting in inadequate global semantic awareness. To address these limitations, we propose RDNet, a retrospective detail network composed of a backward detail reconstruction (BDR) module and a cascaded synergistic optimization (CSO) module. The BDR module injects discriminative semantic information backward in a layer-wise manner to recover weak-response regions that are suppressed during forward propagation, while cross-layer feature calibration enables accurate reactivation of shallow structural details. The CSO module further decouples boundary and region representations and employs a conditional gating mechanism to selectively activate complementary features, thereby enhancing structural consistency and semantic discrimination. Extensive experiments conducted on five public benchmark datasets demonstrate that RDNet consistently outperforms state-of-the-art methods, with particularly significant improvements in fractal-like multi-polyp segmentation scenarios, validating its robustness and effectiveness in complex clinical environments.

Histone H1 promotes silencing of unintegrated HIV-1 DNA

In eukaryotic cells, genomic DNA is packaged into chromatin with nucleosomes formed by core histones H2A, H2B, H3, and H4, and further stabilized by the linker histone H1. During the early stages of retroviral infection, such as with murine leukemia virus (MLV) and human immunodeficiency virus type 1 (HIV-1), host core and H1 histones are rapidly deposited onto unintegrated viral DNAs upon nuclear entry. These unintegrated viral DNAs are transcriptionally silenced through histone posttranslational modifications (PTMs), including high levels of H3K9 trimethylation and low levels of H3 acetylation. Linker histone H1 is closely associated with chromatin compaction and histone PTMs, suggesting a potential role in regulating retroviral DNA fate. In this study, we demonstrate that simultaneous knockdown of four somatic H1 variants (H1.2, H1.3, H1.4, and H1.5) in K562 cells reverses the silencing of unintegrated HIV-1 DNA, resulting in increased viral expression. Notably, this effect was specific to HIV-1, as the same H1 depletion did not alter the silencing of MLV unintegrated DNA. Furthermore, inhibition of H3K9 methylation also relieved HIV-1 silencing, and H1 depletion reduced H3K9me3 deposition on HIV-1 unintegrated DNA. These findings indicate that H1 regulates HIV-1 unintegrated DNA expression by promoting H3K9me3 deposition, a mechanism that appears distinct from that of MLV.