Search Results (1,669)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk. Full article

As typical environmental hormones, endocrine-disrupting chemicals (EDCs) have become a global environmental health issue of high concern due to their property of interfering with the endocrine systems of organisms. As a commonly used substitute for bisphenol A (BPA), bisphenol E (BPE) has been frequently detected in environmental matrices such as soil and water in recent years. Existing research has unveiled the developmental and reproductive toxicity of BPE; however, only one in vitro cellular experiment has preliminarily indicated potential neurotoxic risks, with its underlying mechanisms remaining largely unelucidated in the current literature. Potential toxic mechanisms and action targets of BPE were predicted using the zebrafish model via network toxicology and molecular docking, with RT-qPCRs being simultaneously applied to uncover neurotoxic effects and associated mechanisms of BPE. A significant decrease (p < 0.05) in the frequency of embryonic spontaneous movements was observed in zebrafish at exposure concentrations ≥ 0.01 mg/L. At 72 hpf and 144 hpf, the larval body length began to shorten significantly from 0.1 mg/L to 1 mg/L, respectively (p < 0.01), accompanied by a reduced neuronal fluorescence intensity and a shortened neural axon length (p < 0.01). By 144 hpf, the motor behavior in zebrafish larvae was inhibited. Through network toxicology and molecular docking, HSP90AB1 was identified as the core target, with the cGMP/PKG signaling pathway determined to be the primary route through which BPE induces neurotoxicity in zebrafish larvae. BPE induces neuronal apoptosis and disrupts neurodevelopment by inhibiting the cGMP/PKG signaling pathway, ultimately suppressing the larval motor behavior. To further validate the experimental outcomes, we measured the expression levels of genes associated with neurodevelopment (elavl3, mbp, gap43, syn2a), serotonergic synaptic signaling (5-ht1ar, 5-ht2ar), the cGMP/PKG pathway (nos3), and apoptosis (caspase-3, caspase-9). These results offer crucial theoretical underpinnings for evaluating the ecological risks of BPE and developing environmental management plans, as well as crucial evidence for a thorough comprehension of the toxic effects and mechanisms of BPE on neurodevelopment in zebrafish larvae. Full article

Having in view the current global disruptive social and economic landscape, sustainability becomes more important than ever. As producers become more concerned about adopting more sustainable practices, customer awareness towards sustainable behavior must be the focus of all stakeholders. Within this context, the SHIFT framework (proposed in 2019) highlights the manner in which consumers’ traits and attitudes influence their propensity towards sustainable consumption. It consists of five factors considered to be relevant to consumer behavior: Social influence, Habit formation, Individual self, Feelings and cognition, and Tangibility. Different from previous studies, this research focuses on applying the SHIFT framework to the automotive industry, taking into consideration the contribution of digital technologies to fostering sustainable consumer behavior throughout the entire product lifecycle. Using a qualitative research approach, the most relevant digital technologies in the automotive industry were identified and mapped in relation to the three phases of consumption (choice, usage, and disposal). The research aimed to develop and test an original conceptual framework, starting from the SHIFT. The results of the study highlight the fact that the digital technologies, in their diversity, are integrated in different ways into each of the three phases, facilitating the adoption of sustainable consumption. To achieve sustainability, the two key stakeholders, consumers and producers, should share a common ground on capitalizing the opportunities offered by digital technologies. Full article

To investigate temporal deformation mechanisms of hydraulic asphalt concrete slope flow under evolving temperatures, this study developed a novel temperature-controlled slope flow intelligent test apparatus. Using this apparatus, slope flow tests were conducted at four temperature levels: 20 °C, 35 °C, 50 °C, and 70 °C. By applying nonlinear dynamics theory, the temporal evolution of slope flow deformation and its nonlinear mechanical characteristics under varying temperatures were thoroughly analyzed. Results indicate that the thermal stability of hydraulic asphalt concrete is synergistically governed by the phase-transition behavior between asphalt binder and aggregates. Temporal evolution of slope flow exhibits a distinct three-stage pattern as follows: rapid growth (0~12 h), where sharp temperature rise disrupts the primary skeleton of coarse aggregates; decelerated growth (12~24 h), where an embryonic secondary skeleton forms and progressively resists deformation; stabilization (>24 h), where reorganization of coarse aggregates is completed, establishing structural equilibrium. The thermal stability temperature influence factor (δ) shows a nonlinear concave growth trend with increasing test temperature. Dynamically, this process transitions sequentially through critical stability, nonlinear stability, period-doubling oscillatory stability, and unsteady states. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

Among the numerous compounds released as a result of human activities, endocrine-disrupting chemicals (EDCs) have attracted particular attention due to their widespread detection in human biological samples and their accumulation across various ecosystems. While early research primarily focused on their effects on reproductive health, it is now evident that EDCs may impact neurodevelopment, altering the integrity of neural circuits essential for cognitive abilities, emotional regulation, and social behaviors. These compounds may elicit epigenetic modifications, such as DNA methylation and histone acetylation, that result in altered expression patterns, potentially affecting multiple generations and contribute to long-term behavioral phenotypes. The effects of EDCs may occur though both direct and indirect mechanisms, ultimately converging on neurodevelopmental vulnerability. In particular, the gut–brain axis has emerged as a critical interface targeted by EDCs. This bidirectional communication network integrates the nervous, immune, and endocrine systems. By altering the microbiota composition, modulating immune responses, and triggering epigenetic mechanisms, EDCs can act on multiple and interconnected pathways. In this context, elucidating the impact of EDCs on neurodevelopmental processes is crucial for advancing our understanding of their contribution to neurological and behavioral health risks. Full article

Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER–mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD. Full article

When emergency incidents, such as bridge damage, abruptly occur on highways and lead to traffic disruptions, the multidimensionality and complexity of driver behaviors present significant challenges to the design of effective emergency response mechanisms. This study introduces a multi-level collaborative emergency mechanism grounded in driver behavior characteristics, aiming to enhance both traffic safety and emergency response efficiency through hierarchical collaboration and dynamic optimization strategies. By capitalizing on human drivers’ perception and decision-making attributes, a driver behavior classification model is developed to quantitatively assess the risk response capabilities of distinct behavioral patterns (conservative, risk-taking, and conformist) under emergency scenarios. A multi-tiered collaborative framework, comprising an early warning layer, a guidance layer, and an interception layer, is devised to implement tailored emergency strategies. Additionally, a rear-end collision risk propagation model is constructed by integrating the risk field model with probabilistic risk assessment, enabling dynamic adjustments to interception range thresholds for precise and real-time emergency management. The efficacy of this mechanism is substantiated through empirical case studies, which underscore its capacity to substantially reduce the occurrence of secondary accidents and furnish scientific evidence and technical underpinnings for emergency management pertaining to highway bridge damage. Full article

Disruption of circadian rhythms by abnormal light exposure and reduced melatonin secretion has been linked to heightened pain sensitivity and opioid tolerance. This study evaluated how environmental light manipulation and exogenous melatonin supplementation influence pain perception and morphine tolerance in a rat model of neuropathic pain induced by partial sciatic nerve transection (PSNT). Rats were exposed to constant darkness, constant light, or a 12 h/12 h light–dark cycle for one week before PSNT surgery. Behavioral assays and continuous intrathecal (i.t.) infusion of morphine, melatonin, or their combination were conducted over a 7-day period beginning immediately after PSNT. On Day 7, after discontinued drugs infusion, an acute intrathecal morphine challenge (15 µg, i.t.) was administered to assess tolerance expression. Constant light suppressed melatonin levels, exacerbated pain behaviors, and accelerated morphine tolerance. In contrast, circadian-aligned lighting preserved melatonin rhythms and mitigated these effects. Melatonin co-infusion attenuated morphine tolerance and enhanced morphine analgesia. Reduced pro-inflammatory cytokine expression and increase anti-inflammatory cytokine IL-10 level and suppressed astrocyte activation were also observed by melatonin co-infusion during morphine tolerance induction. These findings highlight the potential of melatonin and circadian regulation in improving opioid efficacy and reduced morphine tolerance in managing neuropathic pain. Full article

Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the mammary gland, a blunted hormonal response (notably of prolactin), altered progesterone and estrogen dynamics, high leptin levels, and misaligned circadian rhythms contribute significantly to delayed lactogenesis. In addition, mechanical difficulties and psychological factors further hinder effective breastfeeding. This report synthesizes evidence from human epidemiological studies and animal models that elucidate the diverse mechanisms linking maternal obesity to delayed lactogenesis. We review the role of obesity-associated inflammatory mediators in impairing mammary tissue remodeling, the endocrine aberrations that impair lactogenic signaling, the consequences of circadian disruption on hormonal rhythmicity, and the behavioral influences that challenge effective breastfeeding. Finally, we discuss the clinical implications of these findings and propose future research directions targeting endocrine modulation, anti-inflammatory therapy, circadian interventions, and enhanced lactation support strategies for mothers with obesity. Full article

This study examines the extended dissipativity analysis for newly designed mixed traffic systems (MTSs) utilizing the coupling memory sampled-data control (CMSDC) approach. The traffic flow creates a platoon, and the behavior of human-driven vehicles (HDVs) is presumed to adhere to the optimal velocity model, with the acceleration of a single-linked automated vehicle regulated directly by a suggested CMSDC. The ultimate objective of this work is to present a CMSDC approach for optimizing traffic flow amidst disruptions. The primary emphasis is on the proper design of the CMSDC to ensure that the closed-loop MTS is extended dissipative and quadratically stable. A more generalized CMSDC methodology incorporating a time delay effect is created using a Bernoulli-distributed sequence. The existing Lyapunov–Krasovskii functional (LKF) and enhanced integral inequality methods offer sufficient conditions for the suggested system to achieve an extended dissipative performance index. The suggested criteria provide a comprehensive dissipative study, evaluating $L_2-L_{\infty }$, $H_{\infty }$, passivity, and dissipativity performance. A simulation example illustrates the accuracy and superiority of the proposed controller architecture for the MTS. Full article

The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article

Wildlife–vehicle collisions (WVCs) remain a significant cause of animal mortality worldwide, particularly in regions experiencing rapid road network expansion. During the COVID-19 pandemic, a number of studies reported decreased WVC rates, attributing this trend to reduced traffic volumes. However, the validity of the simplified assumption that “fewer vehicles means fewer collisions” remains underexplored from a mechanistic perspective. This study aims to reevaluate that assumption using two simulation-based models that incorporate both the physics of vehicle movement and behavioral parameters of road-crossing animals. Employing an inverse modeling approach with quasi-realistic traffic scenarios, we quantify how vehicle speed, spacing, and animal hesitation affect collision likelihood. The results indicate that approximately 10% of modeled cases contradict the prevailing assumption, with collision risk peaking at intermediate traffic densities. These findings challenge common interpretations of WVC dynamics and underscore the need for more refined, behaviorally informed mitigation strategies. We suggest that integrating such approaches into road planning and conservation policy—particularly under the European Union’s ‘Vision Zero’ framework—could help reduce wildlife mortality more effectively in future scenarios, including potential pandemics or mobility disruptions. Full article

Environmental enrichment is essential for promoting species-specific behaviors and enhancing the welfare of zoo-housed animals. This study examined the behavioral responses of two juvenile male binturongs (Arctictis binturong) at the Minnesota Zoo to three enrichment stimuli: lavender oil (olfactory), thawed fish (olfactory and dietary), and hard-boiled egg (olfactory and dietary). Their behaviors were recorded using scan sampling before and after enrichment exposure, focusing on locomotion, foraging, resting, and visitor visibility. Food-based enrichments, particularly the hard-boiled egg, significantly increased foraging behavior, while lavender oil and thawed fish produced minimal behavioral changes. Locomotion and visibility remained stable across the conditions, although a slight increase in resting was observed with lavender oil. No evidence of scent-marking disruption was noted, and individual differences appeared to influence inactivity levels. These findings highlight the potential of biologically relevant, food-based enrichment to stimulate natural behaviors in binturongs and emphasize the importance of species-specific enrichment strategies. Future research should explore a broader range of olfactory cues, assess long-term behavioral responses, and incorporate physiological measures to further evaluate enrichment impacts on binturong welfare. Full article