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9 pages, 493 KB  
Technical Note
Rapid Agrichemical Inventory via Video Documentation and Large Language Model Identification
by Michael Anastario, Cynthia Armendáriz-Arnez, Lillian Shakespeare Largo, Talia Gordon and Elizabeth F. S. Roberts
Int. J. Environ. Res. Public Health 2025, 22(10), 1527; https://doi.org/10.3390/ijerph22101527 - 5 Oct 2025
Abstract
Background: This technical note presents a methodological approach to agrichemical inventory documentation. It complements exposure assessments in field settings with time-restricted observational periods. Conducted in Michoacán, Mexico, this method leverages large language model (LLM) capabilities for categorizing agrichemicals from brief video footage. Method: [...] Read more.
Background: This technical note presents a methodological approach to agrichemical inventory documentation. It complements exposure assessments in field settings with time-restricted observational periods. Conducted in Michoacán, Mexico, this method leverages large language model (LLM) capabilities for categorizing agrichemicals from brief video footage. Method: Given time-limited access to a storage shed housing various agrichemicals, a short video was recorded and processed into 31 screenshots. Using OpenAI’s ChatGPT (model: GPT-4o®), agrichemicals in each image were identified and categorized as fertilizers, herbicides, insecticides, fungicides, or other substances. Results: Human validation revealed that the LLM accurately identified 75% of agrichemicals, with human verification correcting entries. Conclusions: This rapid identification method builds upon behavioral methods of exposure assessment, facilitating initial data collection in contexts where researcher access to hazardous materials may be time limited and would benefit from the efficiency and cross-validation offered by this method. Further refinement of this LLM-assisted approach could optimize accuracy in the identification of agrichemical products and expand its application to complement exposure assessments in field-based research, particularly as LLM technologies rapidly evolve. Most importantly, this Technical Note illustrates how field researchers can strategically harness LLMs under real-world time constraints, opening new possibilities for rapid observational approaches to exposure assessment. Full article
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24 pages, 1307 KB  
Article
Bolus MPTP Injection in Aged Mice to Mimic Parkinson Disease: Effects of Low-Dose Antioxidant Treatment with Fullerene (C60) and Fullerenol (C60(OH)24)
by Tatyana Strekalova, Alisa Burova, Anna Gorlova, Kirill Chaprov, Anastasia Khizeva, Joana E. Coelho, Evgeniy Svirin, Polina Novikova, Lia Ohanyan, Johannes J. M. P. de Munter, Naira Aivazyan, Luisa V. Lopes, Aleksei Umriukhin, Gohar Arajyan and Harry W. M. Steinbusch
Biomedicines 2025, 13(10), 2425; https://doi.org/10.3390/biomedicines13102425 - 3 Oct 2025
Abstract
Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for [...] Read more.
Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C60 and fullerenol C60(OH)24, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article
(This article belongs to the Special Issue Animal Models for Neurological Disease Research)
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18 pages, 602 KB  
Article
Mixed Management in Growing and Finishing Pigs: Impacts on Social Behavior and Judgment Bias
by Angela Cristina da Fonseca de Oliveira, Leandro Batista Costa, Saulo Henrique Weber and Antoni Dalmau
Animals 2025, 15(19), 2893; https://doi.org/10.3390/ani15192893 - 3 Oct 2025
Abstract
Intensive pig production practices may shape cognition and behavior. We evaluated whether repeated regrouping (mixing) and gender (gilts vs. barrows) affect social interactions, fear-related responses, and affective state. A total of 96 growing pigs were separated into two treatments: control—pigs that were mixed [...] Read more.
Intensive pig production practices may shape cognition and behavior. We evaluated whether repeated regrouping (mixing) and gender (gilts vs. barrows) affect social interactions, fear-related responses, and affective state. A total of 96 growing pigs were separated into two treatments: control—pigs that were mixed once during the growing–finishing period; and social stress—pigs that were mixed thrice during the growing–finishing period. Social and non-social behaviors were directly noted, and four behavioral tests were conducted: open field, novel object, couples, and judgment bias tests. The statistical analysis compared gender and treatment, and p-values ≤ 0.05 were considered significant. Females stayed longer in the test pen entrance area during the novel object test and barrows spent more time at the feeder and defecated more during the couples’ test. With regard to the judgment bias test, females took longer to be considered trained in the discriminatory learning task and presented a “pessimistic judgment” during the ambiguous cue. Our results suggest that gender influences judgment bias in pigs and can influence social and non-social behavior, which may reflect a negative affective state with implications for their welfare and management. Full article
16 pages, 1280 KB  
Article
Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury
by Bin Bu, Ruiyao Ma, Chengyu Wang, Shukun Jiang and Xiaoming Xu
Biomolecules 2025, 15(10), 1408; https://doi.org/10.3390/biom15101408 - 2 Oct 2025
Abstract
Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression [...] Read more.
Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved. Methods: A controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels. Results: The expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity. Conclusions: Our research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI. Full article
20 pages, 345 KB  
Article
A Novel Approach to Polynomial Approximation in Multidimensional Cylindrical Domains via Generalized Kronecker Product Bases
by Mohra Zayed
Axioms 2025, 14(10), 750; https://doi.org/10.3390/axioms14100750 - 2 Oct 2025
Abstract
The Kronecker product has been commonly seen in various scientific fields to formulate higher-dimensional spaces from lower-dimensional ones. This paper presents a generalization of the Cannon–Kronecker product bases by introducing generalized Kronecker product bases of polynomials within an analytic framework. It investigates the [...] Read more.
The Kronecker product has been commonly seen in various scientific fields to formulate higher-dimensional spaces from lower-dimensional ones. This paper presents a generalization of the Cannon–Kronecker product bases by introducing generalized Kronecker product bases of polynomials within an analytic framework. It investigates the convergence behavior of infinite series formed by these generalized products in various polycylindrical domains, including both open and closed configurations. The paper also delves into essential analytic properties such as order, type, and the Tρ-property to analyze the growth and structural characteristics of these bases. Moreover, the theoretical insights are applied to a range of classical special functions, notably Bernoulli, Euler, Gontcharoff, Bessel, and Chebyshev polynomials. Full article
26 pages, 4563 KB  
Article
Personalized Smart Home Automation Using Machine Learning: Predicting User Activities
by Mark M. Gad, Walaa Gad, Tamer Abdelkader and Kshirasagar Naik
Sensors 2025, 25(19), 6082; https://doi.org/10.3390/s25196082 - 2 Oct 2025
Abstract
A personalized framework for smart home automation is introduced, utilizing machine learning to predict user activities and allow for the context-aware control of living spaces. Predicting user activities, such as ‘Watch_TV’, ‘Sleep’, ‘Work_On_Computer’, and ‘Cook_Dinner’, is essential for improving occupant comfort, optimizing energy [...] Read more.
A personalized framework for smart home automation is introduced, utilizing machine learning to predict user activities and allow for the context-aware control of living spaces. Predicting user activities, such as ‘Watch_TV’, ‘Sleep’, ‘Work_On_Computer’, and ‘Cook_Dinner’, is essential for improving occupant comfort, optimizing energy consumption, and offering proactive support in smart home settings. The Edge Light Human Activity Recognition Predictor, or EL-HARP, is the main prediction model used in this framework to predict user behavior. The system combines open-source software for real-time sensing, facial recognition, and appliance control with affordable hardware, including the Raspberry Pi 5, ESP32-CAM, Tuya smart switches, NFC (Near Field Communication), and ultrasonic sensors. In order to predict daily user activities, three gradient-boosting models—XGBoost, CatBoost, and LightGBM (Gradient Boosting Models)—are trained for each household using engineered features and past behaviour patterns. Using extended temporal features, LightGBM in particular achieves strong predictive performance within EL-HARP. The framework is optimized for edge deployment with efficient training, regularization, and class imbalance handling. A fully functional prototype demonstrates real-time performance and adaptability to individual behavior patterns. This work contributes a scalable, privacy-preserving, and user-centric approach to intelligent home automation. Full article
(This article belongs to the Special Issue Sensor-Based Human Activity Recognition)
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15 pages, 1328 KB  
Article
Schinus terebinthifolia Raddi. Leaf Lectin (SteLL) Demonstrates Anxiolytic and Antidepressant Effects Under Monoaminergic Deficiency Induced by Reserpine
by Bárbara Raíssa Ferreira de Lima, Leydianne Leite de Siqueira Patriota, Amanda de Oliveira Marinho, Thiago Lucas da Silva Lira, Jainaldo Alves da Costa, Beatriz Galdino Ribeiro, Daniella Carla Napoleão, Jorge Vinícius Fernandes Lima Cavalcanti, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rego, Maira Galdino da Rocha Pitta, Thiago Henrique Napoleão, Michelle Melgarejo da Rosa and Patrícia Maria Guedes Paiva
Plants 2025, 14(19), 3048; https://doi.org/10.3390/plants14193048 - 1 Oct 2025
Abstract
Schinus terebinthifolia Raddi. leaf lectin (SteLL) has been investigated for its neuromodulatory effects. Given the etiological diversity of depression, this study evaluated the effects of SteLL in a pharmacological model induced by reserpine. Mice were administered reserpine intraperitoneally for 10 days to induce [...] Read more.
Schinus terebinthifolia Raddi. leaf lectin (SteLL) has been investigated for its neuromodulatory effects. Given the etiological diversity of depression, this study evaluated the effects of SteLL in a pharmacological model induced by reserpine. Mice were administered reserpine intraperitoneally for 10 days to induce anxiety- and depression-like symptoms. Before reserpine administration, animals also received SteLL (2 or 4 mg/kg, i.p.) or fluoxetine (10 mg/kg, i.p.) for 10 days. Behavioral assessments included the open field test, elevated plus maze, and tail suspension test. Body weight variation and brain levels of cytokines, noradrenaline, dopamine, and serotonin were also analyzed. In reserpine-treated mice, SteLL administration (2 and 4 mg/kg) produced anxiolytic-like effects in the open field (reduced number of rearings) and elevated plus maze (increased time spent in open arms) and significantly reduced immobility time in the tail suspension test. Additionally, SteLL prevented the body weight loss typically induced by reserpine. SteLL treatment modulated neuroinflammation by reducing IL-2 and increasing IL-10 levels in the brain. SteLL treatment restored dopaminergic and noradrenergic levels, with no effect on serotonin. In conclusion, SteLL was effective in reserpine-induced monoaminergic depletion, reversing behavioral and biochemical alterations characteristic of depression, likely through dopaminergic, noradrenergic, and anti-inflammatory mechanisms. Full article
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22 pages, 4256 KB  
Article
Carbon Monoxide in an Experimental Model of Chronic Pelvic Pain Syndrome: The Effects of CORM-A1 on Pain and Anxiety-Related Behaviors
by Nikola Šutulović, Neriman Ezgin, Nela Puškaš, Emilija Đurić, Željko Grubač, Daniel Škrijelj, Milena Vesković, Dušan Mladenović, Isidora Savić, Djuro Macut, Yavuz Dodurga, Aleksandra Rašić-Marković, Olivera Stanojlović and Dragan Hrnčić
Pathophysiology 2025, 32(4), 53; https://doi.org/10.3390/pathophysiology32040053 - 1 Oct 2025
Abstract
Current standard treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a urological disorder with anxiety as a major comorbidity, are limited in success rates. Recent findings revealed the anti-inflammatory and neuroprotective effects of CO-releasing molecules (CO-RMs), but there is a gap in the [...] Read more.
Current standard treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a urological disorder with anxiety as a major comorbidity, are limited in success rates. Recent findings revealed the anti-inflammatory and neuroprotective effects of CO-releasing molecules (CO-RMs), but there is a gap in the knowledge on its effects in CP/CPPS. Therefore, the objective of our study was to investigate the potential therapeutic effects of CORM-A1 on the scrotal pain threshold and anxiety-related behaviors in experimental model of CP/CPPS. Adult Wistar albino male rats were randomized to Sham (intraprostatic saline) or CP/CPPS (intraprostatic λ-carrageenan) groups (n = 12). Half received CORM-A1 (2 mg/kg/day, i.p., days 1–7), others PBS, forming four subgroups (n = 6). The pain threshold (by an electronic von Frey esthesiometer) and anxiety-like behavior (by an open field, elevated plus maze and light/dark test) were assessed; prostates were histologically examined. Carrageenan-induced CP/CPPS caused significant mechanical pain hypersensitivity (p < 0.001), anxiety-like behaviors (p < 0.001–0.05), and histological prostate damage when compared to corresponding Sham groups. CORM-A1 treatment increased pain thresholds (p < 0.001) and improved behavioral outcomes (p < 0.001–0.01) in all ethological tests. These findings indicate that CORM-A1 exerts analgesic and anxiolytic effects in an experimental model of CP/CPPS in rats. Full article
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27 pages, 7591 KB  
Article
Switching Frequency Figure of Merit for GaN FETs in Converter-on-Chip Power Conversion
by Liron Cohen, Joseph B. Bernstein, Roni Zakay, Aaron Shmaryahu and Ilan Aharon
Electronics 2025, 14(19), 3909; https://doi.org/10.3390/electronics14193909 - 30 Sep 2025
Abstract
Power converters are increasingly pushing toward higher switching frequencies, with current designs typically operating between tens of kilohertz and a few megahertz. The commercialization of gallium nitride (GaN) power transistors has opened new possibilities, offering performance far beyond the limitations of conventional silicon [...] Read more.
Power converters are increasingly pushing toward higher switching frequencies, with current designs typically operating between tens of kilohertz and a few megahertz. The commercialization of gallium nitride (GaN) power transistors has opened new possibilities, offering performance far beyond the limitations of conventional silicon devices. Despite this promise, the potential of GaN technology remains underutilized. This paper explores the feasibility of achieving sub-gigahertz switching frequencies using GaN-based switch-mode power converters, a regime currently inaccessible to silicon-based counterparts. To reach such operating speeds, it is essential to understand and quantify the intrinsic frequency limitations imposed by GaN device physics and associated parasitics. Existing power conversion topologies and control techniques are unsuitable at these frequencies due to excessive switching losses and inadequate drive capability. This work presents a detailed, systematic study of GaN transistor behavior at high frequencies, aiming to identify both fundamental and practical switching limits. A compact analytical model is developed to estimate the maximum soft-switching frequency, considering only intrinsic device parameters. Under idealized converter conditions, this upper bound is derived as a function of internal losses and the system’s target efficiency. From this, a soft-switching figure of merit is proposed to guide the design and layout of GaN field-effect transistors for highly integrated power systems. The key contribution of this study lies in its analytical insight into the performance boundaries of GaN transistors, highlighting the roles of parasitic elements and loss mechanisms. These findings provide a foundation for developing next-generation, high-frequency, chip-scale power converters. Full article
(This article belongs to the Topic Wide Bandgap Semiconductor Electronics and Devices)
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17 pages, 2025 KB  
Article
Cerebellar Mechanisms Underlying Autism-like Cognitive Deficits in Mouse Offspring with Prenatal Valproic Acid Exposure
by Juan Wang, Xu-Lan Zhou, Zi-Han Ma, Li Liu, Qian Zhou, Jia-Wei Wen, Jia-Hui Wen, Hui Su, Yu-Han Zhang and Xiao-Chun Xia
Toxics 2025, 13(10), 833; https://doi.org/10.3390/toxics13100833 - 30 Sep 2025
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication and repetitive behaviors, involving various brain regions. Emerging evidence highlights the critical role of the cerebellum in the pathophysiology of autism; however, the underlying molecular mechanisms remain poorly [...] Read more.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication and repetitive behaviors, involving various brain regions. Emerging evidence highlights the critical role of the cerebellum in the pathophysiology of autism; however, the underlying molecular mechanisms remain poorly understood. This study aimed to establish a prenatal valproic acid (VPA)-induced mouse model of ASD and explore the potential molecular mechanisms underlying cerebellar ASD-like phenotypes through DIA-based proteomics and bioinformatics analyses. Significant cognitive impairment and anxiety-like behaviors were detected using an open field test and novel object test following VPA exposure, respectively. Additionally, reduced numbers of Purkinje cells with irregular arrangement were observed in the cerebellum. Furthermore, cerebellar proteomics analyses revealed that they identified 193 differentially expressed proteins (DEPs) involved in multiple pathways, including axon guidance, glutamatergic synapse, long-term potentiation, and calcium signaling, among others. Notably, dysfunction of glutamate receptor signaling and disruptions in axon-guidance signaling appear to be major molecular mechanisms underlying cerebellar impairment. Together, these findings suggest that Grin2b may serve as a critical molecule linking synaptic neurotransmission and neurodevelopmental disorders. Thus, Grin2b may represent a potential therapeutic target for addressing cognitive impairment in ASD. Full article
(This article belongs to the Section Neurotoxicity)
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26 pages, 5170 KB  
Article
Minocycline Treatment Improves Memory and Reduces Anxiety by Lowering Levels of Brain Amyloid Precursor Protein and Indoleamine 2,3-Dioxygenase in a Rat Model of Streptozotocin-Induced Alzheimer’s Disease
by Grzegorz Świątek, Jowita Nowakowska-Gołacka, Monika Słomińska-Wojewódzka, Wojciech Glac, Oliwia Harackiewicz, Ewelina Kurowska-Rucińska and Danuta Wrona
Int. J. Mol. Sci. 2025, 26(19), 9397; https://doi.org/10.3390/ijms26199397 - 26 Sep 2025
Abstract
Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) [...] Read more.
Minocycline (MINO), a classic antibiotic, may have psychotropic activity related to the modulation of the tryptophan-kynurenine pathway. In this study, we investigated the effects of MINO on (1) memory and anxiety behaviors, (2) the modulation of brain levels of amyloid precursor protein (APP) and 2,3-indoleamine dioxygenase (IDO1) levels, and (3) peripheral inflammatory markers in a streptozotocin (STZ)-induced rat model of sporadic Alzheimer’s disease (sAD). After repeated treatment with a dose of 35 mg/kg MINO for seven consecutive days, male Wistar rats with sAD showed (1) improvements in early (29 days after injection, probe test) reference memory (decreased latency to reach the platform, increased time in the critical quadrant of the Morris water maze) and anxiety disorders (increased time in the open arms of the elevated plus maze; increased exploration and entrances in the center of the white–light illuminated open field) 45–46 and 90–91 days after STZ injection; (2) reduced APP and IDO1 levels in the hippocampus and prefrontal cortex; and (3) induction of anti-inflammatory response in blood (increased TCD4+ lymphocyte number and interleukin-10 production). This suggests that MINO, due to its anti-inflammatory action, improves memory and anxiety behavior related to sAD, indicating its neuroprotective and psychotropic properties. Full article
(This article belongs to the Special Issue Drug Repurposing: Emerging Approaches to Drug Discovery (2nd Edition))
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30 pages, 7119 KB  
Article
FLAC3D-IMASS Modelling of Rock Mass Damage in Unsupported Underground Mining Excavations: A Safety Factor-Based Framework
by Mahdi Saadat, Mattin Khishvand and Andrew Seccombe
Mining 2025, 5(4), 60; https://doi.org/10.3390/mining5040060 - 24 Sep 2025
Viewed by 31
Abstract
The implementation and application of a safety factor (SF)-based numerical framework in FLAC3D-IMASS (Itasca Model for Advanced Strain Softening) is presented for the evaluation of the short-term stability of unsupported underground excavations in sedimentary rock masses during pillar recovery in bord-and-pillar mining. The [...] Read more.
The implementation and application of a safety factor (SF)-based numerical framework in FLAC3D-IMASS (Itasca Model for Advanced Strain Softening) is presented for the evaluation of the short-term stability of unsupported underground excavations in sedimentary rock masses during pillar recovery in bord-and-pillar mining. The stability of underground openings during the initial hours post-excavation must be ensured, as they are not accessed thereafter; therefore, short-term stability assessment is essential. The framework was specifically calibrated to field observations and applied to a case study from an Australian bord-and-pillar mine, focusing on plunge and bellout configurations commonly used during the pillar extraction stage to enhance ore recovery. The modelling approach was integrated with rock mass degradation behavior under static loading conditions and was used to calculate three-dimensional distributions of SF to identify potential failure zones. The results demonstrate that the coal (CO) roof scenario generally maintains structural stability, while the impure coal (Cox) roof scenario is observed to exhibit significant instability, particularly at greater excavation advancement. Among the tested bellout geometries, 8.0 m spans were observed to provide improved performance due to shorter tunnel lengths that enhance confinement and reduce the volume of disturbed rock. Overall, the proposed SF framework effectively captures localized failure mechanisms and is demonstrated as a practical design tool for assessing the short-term stability of unsupported structures during critical stages of underground mining operations. Full article
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24 pages, 5557 KB  
Article
The Antidepressant Effect of Targeted Release of Ketamine-Loaded Nanodroplets Stimulated by Low-Intensity Focused Ultrasound
by Bailing Wu, Yu Xu, Yuhang Xie, Youzhuo Li, Yue Huang, Yuran Feng and Mei Zhu
Pharmaceutics 2025, 17(10), 1251; https://doi.org/10.3390/pharmaceutics17101251 - 24 Sep 2025
Viewed by 91
Abstract
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose [...] Read more.
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article
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30 pages, 668 KB  
Article
Symmetry-Aware Transformers for Asymmetric Causal Discovery in Financial Time Series
by Wenxia Zheng and Wenhe Liu
Symmetry 2025, 17(10), 1591; https://doi.org/10.3390/sym17101591 - 24 Sep 2025
Cited by 1 | Viewed by 111
Abstract
Financial markets exhibit fundamental asymmetries in temporal causality, where policy interventions create asymmetric transmission patterns that traditional symmetric modeling approaches fail to capture. This work introduces a mathematical framework that exploits the inherent symmetries of transformer architectures while preserving essential asymmetric temporal relationships [...] Read more.
Financial markets exhibit fundamental asymmetries in temporal causality, where policy interventions create asymmetric transmission patterns that traditional symmetric modeling approaches fail to capture. This work introduces a mathematical framework that exploits the inherent symmetries of transformer architectures while preserving essential asymmetric temporal relationships in financial causal inference. We develop CausalFormer, a symmetry-aware neural architecture that maintains the permutation equivariance properties of self-attention mechanisms while enforcing strict temporal asymmetry constraints for causal discovery. The framework incorporates three mathematically principled components: (1) a symmetric attention matrix construction with asymmetric temporal masking that preserves the mathematical elegance of transformer operations while ensuring causal consistency, (2) a multi-scale convolution module with symmetric kernel initialization but asymmetric temporal receptive fields that captures policy transmission effects across heterogeneous time horizons, and (3) enhanced Nelson–Siegel decomposition that maintains the symmetric factor structure while modeling the evolution dynamics of asymmetric factors. Our mathematical formulation establishes the formal symmetry properties of the attention mechanism under temporal transformations while proving asymmetric convergence behaviors in policy transmission scenarios. The integration of symmetric optimization landscapes with asymmetric causal constraints enables simultaneous achievement of mathematical elegance and economic interpretability. Comprehensive experiments on monetary policy datasets demonstrate that the symmetry-aware design achieves a 15.3% improvement in the accuracy of causal effect estimations and a 12.7% enhancement in the predictive performance compared to those for existing methods while maintaining 91.2% causal consistency scores. The framework successfully identifies asymmetric policy transmission mechanisms, revealing that monetary tightening exhibits 40% faster propagation than easing policies, establishing new mathematical insights into the temporal asymmetries in financial systems. This work demonstrates how principled exploitation of architectural symmetries combined with domain-specific asymmetric constraints opens up new directions for mathematically rigorous yet economically interpretable deep learning in financial econometrics, with broad applications spanning computational finance, economic forecasting, and policy analysis. Full article
(This article belongs to the Section Mathematics)
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17 pages, 6419 KB  
Article
Lactiplantibacillus plantarum HY7715 Alleviates Restraint Stress-Induced Anxiety-like Behaviors by Modulating Oxidative Stress, Apoptosis, and Mitochondrial Function
by Kippuem Lee, Daehyeop Lee, Haeryn Jeong, Joo Yun Kim, Jae Jung Shim and Jae Hwan Lee
Int. J. Mol. Sci. 2025, 26(18), 9251; https://doi.org/10.3390/ijms26189251 - 22 Sep 2025
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Abstract
Anxiety disorders are closely associated with oxidative stress-mediated neuronal damage, mitochondrial dysfunction, and apoptosis. In this study, we investigated the neuroprotective effects of Lactiplantibacillus plantarum HY7715 in a mouse model of restraint stress-induced anxiety, and in neuronal cell models (HT-22 mouse hippocampal neuroblast [...] Read more.
Anxiety disorders are closely associated with oxidative stress-mediated neuronal damage, mitochondrial dysfunction, and apoptosis. In this study, we investigated the neuroprotective effects of Lactiplantibacillus plantarum HY7715 in a mouse model of restraint stress-induced anxiety, and in neuronal cell models (HT-22 mouse hippocampal neuroblast cell and SH-SY5Y human neuroblastoma cells). Oral administration of HY7715 (1 × 109 CFU/kg/day) alleviated anxiety-like behaviors significantly, as shown by increased central exploration in the open field test and prolonged open-arm activity in the elevated plus maze. HY7715 reduced serum norepinephrine levels elevated by stress, and restored hippocampal expression of brain-derived neurotrophic factor, while suppressing pro-inflammatory (NF-κB, IL-6) and pro-apoptotic (BAX, caspase-3) markers. It also increased expression of mitochondrial regulatory genes (SIRT1, mTOR), and decreased that of cytochrome c, in brain tissue. Histological analysis revealed that HY7715 preserved neuronal integrity in the CA1 and CA3 hippocampal regions. In vitro, HY7715 attenuated oxidative stress-induced cytotoxicity, decreased intracellular ROS accumulation, maintained mitochondrial activity, and inhibited apoptosis of both neuronal cell types, showing greater efficacy than the strain type L. plantarum KCTC3108. These findings suggest that HY7715 exerts neuroprotective effects by modulating oxidative stress/apoptosis/mitochondrial pathways, and highlight its potential as a psychobiotic for stress-related neuropsychiatric disorders. Full article
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