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Extreme stressor-evoked psychophysiological responses are associated with adverse health outcomes. The present study examined the individual and combined influence of exercise and arousal reappraisal on stressor-evoked psychophysiological responses. Participants (N = 238) were randomly assigned to one of four groups: control (CTRL), arousal reappraisal only (AR), exercise only (EX), or combined arousal reappraisal and exercise (AR + EX). After completing baseline 1, the assigned experimental condition, recovery, and baseline 2, participants underwent a speech task. Cardiovascular measures were obtained during baselines and the stress task, and state psychological measures were obtained after informed consent and after the stress task. Trait reappraisal was also measured. There were no group differences in stressor-evoked cardiovascular responses. However, despite similar stress intensity ratings across all groups, participants in the AR group interpreted their stress more positively. Additionally, moderation analyses demonstrated that individuals with higher trait reappraisal in the EX and AR + EX groups viewed their physiological arousal as more helpful than individuals in the CTRL group. Arousal reappraisal may improve interpretations of acute stress. Additionally, acute exercise may be most beneficial for reducing negative interpretations of perceived physiological arousal when trait reappraisal levels are high. Future research should explore whether repeated arousal reappraisal and exercise training may promote more adaptive stressor-evoked responses.

The thyroid hormone system regulates physiological processes that are crucial for growth and metabolism. The homeostasis of thyroid hormones can be affected by test substances via multiple molecular interactions, one of them being the displacement of thyroid hormones from their binding proteins. The main thyroid hormone in the human bloodstream is L-thyroxine (T4), ≥ 99.5% of which is transported bound to three proteins: thyroxine binding globulin (TBG), transthyretin (TTR) and human serum albumin (HSA). To investigate the interactions of xenobiotics with the binding of T4 to these proteins, an in vitro thyroid hormone protein binding assay (THPB-assay) was developed. Samples containing 100 nM T4 were incubated with a T4-binding protein and increasing concentrations of a test compound, followed by removal of the unbound T4 via size exclusion chromatography and analysis of protein-bound T4. This assay allows for multiple adjustable parameters, including the choice of binding protein and the detection method for protein-bound T4, which can be extracted and measured via LC-MS or, when using 125I-T4, by a gamma counting. Eight test substances were tested for the displacement of T4 from TTR and TBG respectively. For interference with T4-TTR binding, Tetrabromobisphenol A was established as a positive control with an average measured IC50 of 287 nM. Displacement of T4 was observed for five more test substances, which displaced T4 from TTR with IC50 ranging from 101 nM for Tetrac and 121 nM for 2,4,6-tribromophenol (TBP) to 1056 nM for Genistein. 6-propylthiouracil and L-DOPA did not displace T4 from TTR. LC-MS analysis and gamma counting of 125I-T4 yielded similar results for each test substance. The five test substances which displaced T4 from TTR were additionally tested for displacement of T4 from TBG. Tetrac and Benziodarone displaced T4 with IC50 values of 3 µM and 22 µM, respectively, whereas the remaining compounds did not. Finally, a mix of TTR, TBG and HSA, in concentrations of 536 nM, 26.5 nM and 65.35 µM respectively, was tested with the potent T4 displacer Tetrac. Tetrac displaced T4 from this protein mix with an IC50 of 154 µM. Using the radioligand detection method, the T4 displacement of compounds from human and rat serum was tested to elucidate their effect in a physiological environment and identify potential species differences. Tetrac displaced T4 from human and rat serum at 10% serum concentration in samples, with IC50 values of 38 µM and 242 µM respectively. TBP displaced T4 from 10% rat serum with an IC50 of 1.3 mM. No displacement was observed in 10% human serum. At higher serum concentrations, no test substance was measured to displace T4 regardless of the species. While further research is essential, the insights regarding the absence of displacement at physiological serum concentrations challenge current risk assessment frameworks, which define changes in serum T4 levels as a key event in adverse outcome pathways related to the displacement of T4 from TTR.

Aging is associated with structural and functional changes of the vocal folds that may result in presbyphonia, often perceived as a weak or shaky voice. However, the quantitative characterization of underlying age-related vocal tremor across the adult lifespan remains limited. This cross-sectional study investigated the characteristics of vocal tremor across the adult lifespan using automated acoustic analysis. A total of 291 native speakers aged 18-94 years were recruited and underwent perceptual voice evaluation and acoustic analysis during sustained phonation of the vowel /a/. Vocal tremor was quantified using digital signal processing, focusing on the prominence of fundamental frequency tremor (PF0T) and the prominence of amplitude tremor (PAT). A moderate-to-strong positive correlation between age and PF0T was observed in both males and females, indicating increasing instability of fundamental frequency with advancing age. In contrast, PAT did not show a significant age-related increase after correction for multiple comparisons. Perceptual ratings of tremor demonstrated only weak correlations with age but were moderately associated with acoustic measures of tremor. Normative models revealed that physiological tremor in healthy aging remains well below pathological thresholds reported in neurological disorders. These findings indicate that age-related vocal tremor is characterized predominantly by increasing instability of fundamental frequency rather than amplitude modulation, localizing the dominant age effect to laryngeal control of vocal fold tension rather than to respiratory drive. Automated acoustic analysis provides a sensitive and objective method for detecting subtle age-related vocal changes and may support future biomarker development for distinguishing physiological from pathological vocal tremor.

Bone remodeling in the mandible is governed by the interplay between local mechanical loads, cellular population dynamics, and overload-induced resorption. While mastication is the primary physiological driver of mandibular adaptation, low-magnitude vibration has emerged as a promising noninvasive adjunct to enhance peri-implant bone stability. However, the mechanistic interaction between vibration and chewing-induced stimuli remains insufficiently clarified.This study presents a hybrid mechanobiological model that integrates a reaction-diffusion formulation for osteoblast, osteoclast, and mediator fields with a density evolution law combining adaptive regulation and overload penalization. The framework incorporates accumulated stimulus dynamics, a threshold-regulated lazy zone, and frequency-dependent vibratory modulation of cellular activity. Numerical simulations were performed under controlled physiological and mechanical conditions using spatially resolved density fields and Gaussian-distributed masticatory stresses.The model reproduced the canonical biphasic response of bone adaptation, with an initial anabolic phase followed by stabilization governed by overload-driven resorption. Under chewing alone, the density evolution progressively approached a quasi-stationary regime near 1.02-1.03 g/cm3, depending on load magnitude. When vibration was superimposed, a strong frequency-dependent anabolic effect emerged: 40 Hz increased steady-state density by approximately 3.5%, whereas 120 Hz produced gains near 10% (0.08-0.10 g/cm3), consistent with 80-100 HU changes measurable by CBCT. Spatially, mastication alone generated localized densification, while vibration broadened and homogenized the anabolic region, particularly at 120 Hz. Cellular simulations revealed accelerated and synchronized reductions in osteoblast and osteoclast populations under vibration, indicating enhanced mechanotransductive efficiency rather than increased metabolic demand. The agreement between simulated density gains and spatial adaptation patterns demonstrates that the proposed hybrid model captures key mechanobiological features of mandibular adaptation. The framework offers a rigorous and computationally efficient tool for predicting peri-implant bone remodeling under combined masticatory and vibratory stimuli, supporting the development of patient-specific vibration-based therapeutic strategies in oral and maxillofacial biomechanics.

To analyze the research dynamics of myopia management functional lenses (MMFL) in the field of vision health over the past decade, revealing cutting-edge hotspots and development trends. Relevant literature on MMFL from 2016 to 2025 in the Web of Science (WOS) core database was searched by computer. The bibliometrics software Bibliometrix, VOSviewer 1.6.20 and CiteSpace.V.6.3.R1 were used for bibliometric and knowledge graph visualisation analyses. A total of 1143 WOS core database documents were included, and the number of publications has gradually increased over time. China and the United States rank the top two in terms of the number of publications and citations. The leading authors in this field are Cho P, Sankaridurg P, and Chen H, who have made significant contributions to research in two distinct subfields: contact lenses and spectacle lenses. Most relevant sources are OPHTHALMIC AND PHYSIOLOGICAL OPTICS, CONTACT LENS & ANTERIOR EYE, and OPTOMETRY AND VISION SCIENCE, all of which are considered to be highly authoritative publications in this field. These journals have published a considerable number of articles on a wide range of topics, including the mechanism of spectacle lenses, physiological changes associated with contact lenses, variations in fitting parameters, and the effects of myopia control. The keywords co-occurrence, clustering, thematic map, timeline view and emergent analyses reveal that recent research has been focused on the following areas: axial length, defocusing mechanism, choroidal thickness, and orthokeratology. The knowledge map of research on MMFL is constructed through bibliometric analysis, systematically summarizing the current status and hotspots of research. The integration of material, optics and intelligence is a trend that is set to be reflected in future functional lenses for myopia management.

Circadian rhythms orchestrate a wide array of behavioral and physiological functions, coordinating cellular and organismal processes on an approximately 24-h cycle through an intrinsic timekeeping system. Among the many processes subject to this temporal regulation, mitochondrial function has emerged as a critical and dynamic target of circadian control. Mitochondria, far from being static organelles, undergo continuous morphological remodeling through cycles of fusion and fission, collectively termed mitochondrial dynamics, that are essential for maintaining metabolic homeostasis, energy production, and cellular quality control. Disruptions in circadian rhythmicity, such as those arising from sleep disturbances or irregular feeding patterns, have been associated with impaired glucose tolerance, insulin resistance, and increased risk of metabolic syndrome, diabetes, and cardiovascular disease. Emerging evidence suggests that the circadian clock and mitochondrial dynamics are engaged in a bidirectional interplay, whereby clock-controlled gene expression shapes mitochondrial morphology and function, while mitochondrial metabolic states in turn feedback to influence circadian timing. This review explores the evolutionary origins of mitochondrial rhythmicity, synthesizes current evidence on how the circadian clock regulates mitochondrial dynamics, and examines the physiological and pathological implications of their interconnection. A particular focus is placed on how disruptions in this circadian-mitochondrial axis may contribute to the development of common diseases, including neurodegenerative disorders, metabolic diseases, and cancer, highlighting novel avenues for chronobiologically informed therapeutic strategies.

Melatonin, an anti-inflammatory-antioxidant neurohormone, is considered for the treatment of neonatal hypoxic-ischemic-encephalopathy. However, its effects on the developing cardiopulmonary system are poorly defined. We investigated how postnatal melatonin administration alters cardiopulmonary structure, function, and responses to acute hypoxia in newborn lambs. Twenty term-newborn lambs received melatonin (0.25 mg kg-1, n = 9) or vehicle (n = 11) daily from birth to day 5. Echocardiography was performed in 15 lambs (7 melatonin; 8 vehicle; day 5). On day-6, five lambs per group underwent 30-min of hypoxia followed by euthanasia. Cardiovascular physiology, morphology, cardiomyocyte size, gene expression, and lung morphology were analyzed. At normoxia, melatonin-treated lambs showed normal systemic function but altered cardiac hemodynamics and morphology compared to vehicle-treated lambs. During hypoxia, melatonin-treated lambs exhibited a blunted sympatho-circulatory response, with no increase in mean pulmonary arterial pressure and cardiac output. Additionally, heart weight and cardiomyocyte cross-sectional area were reduced, and pulmonary arteriole density increased. Gene expressions showed reduced cardiomyocyte markers in the right ventricle and left atrium but increased protective gene expression in the left ventricle. Postnatal melatonin triggers notable cardiopulmonary remodeling, reducing physiological flexibility to respond to hypoxic stress, highlighting the need to weigh its therapeutic benefits against potential cardiovascular risks. This study examined the effects of melatonin treatment on the cardiopulmonary system during the early neonatal period in lambs, when endogenous melatonin production is limited. Melatonin induces significant cardiopulmonary remodeling in newborn lambs, characterized by reduced heart weight and ventricular cardiomyocyte size, increased pulmonary arteriole density, and altered cardiac chamber gene expression. While these changes maintain normal cardiovascular function at normoxic-baseline, they compromise the system's ability to respond to acute hypoxia, revealing a diminished physiological flexibility. The study highlights the need to balance melatonin's therapeutic promise with caution regarding its potential developmental consequences on the cardiopulmonary system.

MhbZIP62-MhbZIP23 module has a positive regulatory effect on tobacco and apple calli under drought stress. Drought stress seriously restricts the efficient cultivation and sustainable development of the apple industry. In this study, 19 apple MhbZIP genes were identified from transcriptome datasets, followed by systematic analyses of their physicochemical characteristics, promoter cis-acting elements, and stress-responsive expression profiles. Bioinformatic analysis revealed that most encoded proteins are hydrophilic and unstable, and their promoter regions contain abundant cis-elements responsive to diverse abiotic stresses and phytohormones. Transcriptional assays showed that MhbZIP family genes are markedly upregulated upon PEG 6000, mannitol and ABA treatments, with MhbZIP62 displaying the most prominent inducible expression. Functional assays in transgenic tobacco and apple calli verified that ectopic overexpression of MhbZIP62 substantially improves drought tolerance, elevates endogenous ABA levels, and stimulates antioxidant enzyme activities. Consistently, VIGS-mediated knockdown of MhbZIP62 compromises drought-associated physiological traits, whereas exogenous ABA supplementation partially restores the defective phenotype. Yeast two-hybrid and subsequent biochemical assays validated physical protein-protein interaction between MhbZIP62 and MhbZIP23. In apple calli, co-overexpression of the two genes synergistically strengthens drought resistance relative to single-gene overexpression. Furthermore, transient silencing of MhbZIP23 in apple seedlings leads to aggravated leaf wilting, enlarged stomatal aperture, suppressed antioxidant enzyme activities, and reduced accumulation of proline and chlorophyll, ultimately impairing drought adaptability. Collectively, this work characterizes the drought-resistant functions of MhbZIP62 and MhbZIP23 as well as their synergistic regulation via protein interaction, and phenotypic and physiological data imply potential involvement of ABA-dependent pathways in their drought regulatory cascade, which lays a theoretical foundation for drought-resistant molecular breeding and agronomic improvement in apple.

Beyond inherited genes and environmentally induced changes in gene expression, phenotypes can also be shaped by parental effects-an effect from a parental phenotype that causes modifications in offspring traits, which cannot be solely explained by the parental or offspring genomes. Such effects may prepare offspring for future environmental conditions and contribute to phenotypic plasticity, including responses to temperature. While temperature-induced plasticity has been extensively studied, the relative contributions of parental versus direct environmental cues remain poorly understood. The fruit fly Drosophila melanogaster is a powerful model for studying physiological and behavioral adaptation to temperature. Flies inhabit environments spanning broad thermal ranges and show evidence of parental effects, such as increased heat tolerance in offspring from warm-reared parents. Here, we exposed mothers to two experimental temperatures and split their broods between the same two temperatures to estimate the relative importance of maternal and developmental effects on adult physiological and developmental responses to temperature. We find that the reaction norms of locomotor activity under gradually increasing temperatures, responses to heat-shock and cold-shock, and fecundity are mostly governed by direct plastic responses to developmental environment. We detected comparatively weak maternal effects in the response to heat-shock, fecundity, and grand-offspring survival where matched environments counteracted the effects of direct offspring experience. We conclude that thermal experience during development is the primary determinant of phenotypic plasticity in D. melanogaster, while maternal experience contributes a small but non-negligible component.

Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) cells. Although OLE exhibits direct anticancer effects, its therapeutic utility is constrained by poor bioavailability, requiring supraphysiological concentrations for direct cytotoxicity. To evaluate the effect of OLE on the cytotoxic activity of NK-92 cells against HT-29 colorectal cancer cells within a co-culture model. Olive leaves obtained from Balıkesir, Türkiye were dried and extracted with 70% methanol. The effects of OLE on the viability of HT-29 cells and NK-92 cells were evaluated using MTT and ATP assays. Additionally, the cytotoxic activity of NK-92 cells against HT-29 cells was assessed in a direct co-culture system. Granzyme B and perforin levels were measured using ELISA kits. OLE inhibited the proliferation of HT-29 cells in a dose-dependent manner, with an IC₅₀ values of 548 µg/mL. In NK-92 cells, low concentrations of OLE (100-200 µg/mL) promoted cell proliferation, whereas higher concentrations exerted cytotoxic effects. In co-culture experiments, NK-92-mediated cytotoxicity against HT-29 cells was significantly enhanced by the addition of OLE at non-toxic concentrations (100 and 200 µg/mL). This enhanced cytotoxicity was further supported by a significant increase in granzyme B and perforin levels following OLE treatment. Our findings suggest that OLE can elicit a potent anticancer response via NK cells at lower, physiologically achievable doses. These results highlight a promising therapeutic strategy for CRC, leveraging OLE's immunomodulatory effects to enhance innate antitumor defenses.

Aging disrupts physiological homeostasis, impairing thermoregulation, metabolism, and water balance, but the underlying neural mechanisms remain unclear. Here, we identify arginine vasopressin (AVP) neurons in the supraoptic nucleus (SON) of the hypothalamus as a critical driver of these changes in male mice. Single-nucleus RNA-sequencing revealed Avp among the most upregulated neuronal transcripts with age. Aged SONAVP neurons displayed enlarged size and heightened excitability, features consistent with hyperactivity. Chemogenetic activation of SONAVP neurons in young mice reproduced aging-associated phenotypes including hypothermia, reduced energy expenditure, and suppressed water intake. Conversely, knockdown of Avp in the SON of aged mice restored water balance, partially improved thermoregulation and metabolism. Pharmacological studies demonstrated that neuroendocrine AVP signaling mediates these deficits through distinct contributions of V1A and V2 receptors. These findings identify SONAVP neurons as a central regulator of physiological aging and a potential therapeutic target for age-related homeostatic dysfunction.

In vitro alveolar-capillary models based on co-culturing the alveolar epithelial cell line H441 and primary pulmonary microvascular endothelial cells (HPMEC) are a widely used platform for evaluating the function of the alveolar barrier. However, the relatively thick synthetic membranes that are used as substrates in most approaches fail to mimic the properties of the natural basement membrane, thereby decreasing the physiological relevance of those models. We investigated the potential of the FN-silk membrane to support an in vitro alveolar-capillary model. The FN-silk membrane is micrometer-thin, fibrillar, constructed from a functionalized recombinant spider silk protein, and has been previously shown to be a potent basement membrane mimic supporting physiologically relevant in vitro models of various barrier tissues (i.e., blood vessel, skin, BBB, and kidney). Herein, it supported alveolar epithelial and endothelial barrier formation, surfactant protein B and C (SPB, SPC) production, and epithelial cell polarization, detected with immunofluorescence. Notably, we also demonstrated for the first time, to our knowledge, that key events related to alveologenesis (i.e., cell hollowing, lumen formation, septation, and α-SMA expression) can take place in an in vitro model. This further highlights the ability of the FN-silk membrane to recapitulate the complicated alveolar milieu and expanding the known potential of the H441 cell line, which to our knowledge, has not been previously reported to enable modeling the alveolar tissue 3D morphology. We propose the FN-silk-based alveolar-capillary model as an advanced in vitro model that can be used as a potent tool in respiratory, developmental biology, and regenerative medicine research.

In everyday life, eye movements (including fixation, smooth pursuit and saccades) are essential for interacting with the visual environment. In patients with Disorders of Consciousness (DoC), visual fixation and pursuit are considered among the earliest clinical signs of awareness recovery. However, the traditional distinction between reflexive and voluntary eye movements may be insufficient to interpret these behaviours, as movements that appear automatic can still recruit cortical networks. This review re-examines eye movements in DoC through a neuroanatomical and translational lens. We characterize their physiological parameters, clinical operational definitions and underlying brain networks, with particular attention to the extent of cortical involvement. Across fixation, pursuit and saccades, we show that cortical participation is frequent but does not necessarily imply conscious intention. We therefore propose reframing behavioural interpretation from a reflexive-versus-voluntary dichotomy toward a gradient of cortical mediation, aligned with the concept of Cortically Mediated State. We highlight the differential inferential strength of oculomotor behaviours: fixation may reflect subcortical stabilization, whereas pursuit and structured saccadic paradigms provide stronger evidence of cortical engagement. However, even cortically mediated eye movements do not constitute definitive proof of conscious awareness. Finally, we discuss methodological constraints in bedside assessment, the need for standardized oculometric paradigms, and the complementary role of multimodal approaches, including pupillary dynamics, to better disentangle preserved cortical processing from overt behavioural expression in severe brain injury.