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15 pages, 1849 KB  
Article
Prevalence of Sleep Disturbance and Associated Risk Factors in Degenerative Cervical Myelopathy
by Salim Yakdan, Karan Joseph, Jingyi Zhang, Miguel A. Ruiz-Cardozo, Aryan Pradhan, Alisha Dhallan, Faraz Arkam, Willliam Mualem, Garrison Bentz, Diogo P. Moniz Garcia, Benjamin Plog, Alexander T. Yahanda, Daniel Hafez, Wilson Z. Ray, Camilo A. Molina and Jacob K. Greenberg
J. Clin. Med. 2025, 14(19), 7110; https://doi.org/10.3390/jcm14197110 - 9 Oct 2025
Abstract
Study Design: Retrospective Case–Control. Objectives: Sleep disturbances negatively impact quality of life and increase illness susceptibility. Chronic pain is a risk factor for sleep disruption, particularly in patients with degenerative spinal conditions. Existing studies suggest that degenerative cervical myelopathy (DCM) patients often experience [...] Read more.
Study Design: Retrospective Case–Control. Objectives: Sleep disturbances negatively impact quality of life and increase illness susceptibility. Chronic pain is a risk factor for sleep disruption, particularly in patients with degenerative spinal conditions. Existing studies suggest that degenerative cervical myelopathy (DCM) patients often experience sleep disturbances, possibly due to spinal cord compression and pain. However, most research is limited to small, single-center studies, creating a need for broader analyses. Methods: We utilized the Merative Explorys Dataset, focusing on electronic health record data of patients diagnosed with DCM and sleep disorders identified via ICD codes. Comorbidities analyzed included depression/bipolar disorder, chronic pulmonary disease, migraine, osteoarthritis, hypertension, malignancy, diabetes, and cerebrovascular disease. Patient demographic information (age, race, sex, and body mass index (BMI)) was included as covariates. Logistic regression analyses were performed to evaluate the association between each comorbidity and the risk of sleep disturbance. Results: Among 40,551 DCM patients, significant predictors of sleep disturbance included higher BMI (OR: 1.05, 95% CI: 1.05–1.06), depression/bipolar disorder (OR: 1.65, 95% CI: 1.56–1.74), chronic pulmonary disease (OR: 1.26, 95% CI: 1.20–1.33), migraine (OR: 1.32, 95% CI: 1.22–1.43), and hypertension (OR: 1.16, 95% CI: 1.10–1.23). Conclusions: This large-scale analysis demonstrates the multifactorial nature of sleep disturbances in DCM, highlighting strong associations with BMI and respiratory conditions, suggesting a contributory role of sleep-disordered breathing. The identification of migraines as a risk factor highlights the need for multidisciplinary management. Addressing modifiable risk factors such as BMI and mental health may improve sleep quality in DCM patients. Full article
(This article belongs to the Special Issue Emerging Trends in Cervical Spine Surgery)
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22 pages, 2565 KB  
Review
Inflammatory and Immune Biomarkers in Mood Disorders: From Mechanistic Pathways to Clinical Translation
by Mario Pinzi, Andrea Fagiolini, Despoina Koukouna, Giacomo Gualtieri, Maria Beatrice Rescalli, Caterina Pierini, Simone Pardossi, Benjamin Patrizio and Alessandro Cuomo
Cells 2025, 14(19), 1558; https://doi.org/10.3390/cells14191558 - 8 Oct 2025
Viewed by 134
Abstract
Over the past two decades, immune–inflammatory dysregulation has emerged as a central paradigm in the biology of mood disorders. Patients with major depression (MDD) and bipolar disorder (BD) frequently display low-grade systemic inflammation. Elevated C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α [...] Read more.
Over the past two decades, immune–inflammatory dysregulation has emerged as a central paradigm in the biology of mood disorders. Patients with major depression (MDD) and bipolar disorder (BD) frequently display low-grade systemic inflammation. Elevated C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) identify clinically relevant subgroups of patients characterized by greater severity, cognitive impairment, and poor treatment response. Changes in the gut microbiota and disruptions of the blood–brain barrier (BBB) act as important gateways through which systemic immune activity can influence the brain. At the intracellular level, pattern-recognition receptors activate convergent hubs including NF-κB, JAK/STAT, and MAPK cascades, while the NLRP3 inflammasome integrates mitochondrial dysfunction and oxidative stress with IL-1β release and pyroptosis. These pathways converge on glial dysregulation, impaired BDNF/TrkB signaling, and kynurenine pathway (KP) alterations, fostering excitotoxicity and synaptic deficits. Translational studies demonstrate that elevated CRP and IL-6 predict poor antidepressant outcomes. Anti-inflammatory agents such as infliximab and celecoxib show efficacy in specific subgroups of patients. Emerging multi-omics approaches identify immuno-metabolic biotypes, supporting the rationale for biomarker-guided stratification. These findings define an ‘inflammatory biotype’ of mood disorders and highlight the need for biomarkers and precision-based trials to guide treatment. Full article
(This article belongs to the Special Issue Neuroinflammation in Brain Health and Diseases)
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26 pages, 4387 KB  
Article
Modeling, Analysis, and Classification of Asymmetrical DC Faults in a Bipolar Hybrid Cascaded Multi-Terminal HVDC System
by Muhammad Asim Mond, Zhou Li and Wenwen Mei
Symmetry 2025, 17(10), 1671; https://doi.org/10.3390/sym17101671 - 7 Oct 2025
Viewed by 167
Abstract
Hybrid cascaded multi-terminal HVDC systems represent a significant advancement in HVDC transmission technology. A notable real-world implementation of this concept is the bipolar hybrid cascaded multi-terminal high voltage direct current (MTDC) project in China, which successfully transmits hydropower from Baihetan to Jiangsu. This [...] Read more.
Hybrid cascaded multi-terminal HVDC systems represent a significant advancement in HVDC transmission technology. A notable real-world implementation of this concept is the bipolar hybrid cascaded multi-terminal high voltage direct current (MTDC) project in China, which successfully transmits hydropower from Baihetan to Jiangsu. This system combines MMCs for system support with LCCs for high-power transmission, offering both flexibility and efficiency in long-distance power delivery. This research explores the characteristics of main DC fault types in such systems, classifying faults based on sections and modes while analyzing their unique outcomes depending on DC fault locations. By focusing on the DC-side terminal behavior of the MMCs and LCCs, the main response processes to asymmetrical DC faults are investigated in detail. This study offers a detailed analysis of asymmetrical DC faults in bipolar HVDC systems, proposing a new classification based on fault characteristics such as current, voltage, active power, and reactive power. A supporting theoretical analysis is also presented. It identifies specific control demands needed for effective fault mitigation. PSCAD/EMTDC simulation results demonstrate that DC faults with similar characteristics can be consistently grouped into distinct categories by this new classification method. Each category is further linked to specific control demands, providing a strong basis for developing advanced protection strategies and practical solutions that enhance the stability and reliability of hybrid cascaded HVDC systems. Full article
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18 pages, 5552 KB  
Article
Development of a Low-Cost Measurement System for Soil Electrical Conductivity and Water Content
by Emmanouil Teletos, Kyriakos Tsiakmakis, Argyrios T. Hatzopoulos and Stefanos Stefanou
AgriEngineering 2025, 7(10), 329; https://doi.org/10.3390/agriengineering7100329 - 1 Oct 2025
Viewed by 349
Abstract
Soil electrical conductivity (EC) and water content are key indicators of soil health, influencing nutrient availability, salinity stress, and crop productivity. Monitoring these parameters is critical for precision agriculture. However, most existing measurement systems are costly, which restricts their use in practical field [...] Read more.
Soil electrical conductivity (EC) and water content are key indicators of soil health, influencing nutrient availability, salinity stress, and crop productivity. Monitoring these parameters is critical for precision agriculture. However, most existing measurement systems are costly, which restricts their use in practical field conditions. The aim of this study was to develop and validate a low-cost, portable system for simultaneous measurement of soil EC, water content, and temperature, while maintaining accuracy comparable to laboratory-grade instruments. The system was designed with four electrodes arranged in two pairs and employed an AC bipolar pulse method with a constant-current circuit, precision rectifier, and peak detector to minimize electrode polarization. Experiments were carried out in sandy loam soil at water contents of 13%, 18%, and 22% and KNO3 concentrations of 0, 0.1, 0.2, and 0.4 M. Measurements from the developed system were benchmarked against a professional impedance analyzer (E4990A). The findings demonstrated that EC increased with both frequency and water content. At 100 Hz, the mean error compared with the analyzer was 8.95%, rising slightly to 9.98% at 10 kHz. A strong linear relationship was observed between EC and KNO3 concentration at 100 Hz (R2 = 0.9898), and for the same salt concentration (0.1 M KNO3) at 100 Hz, EC increased from ~0.26 mS/cm at 13% water content to ~0.43 mS/cm at 22%. In conclusion, the developed system consistently achieved <10% error while maintaining a cost of ~€55, significantly lower than commercial devices. These results confirm its potential as an affordable and reliable tool for soil salinity and water content monitoring in precision agriculture. Full article
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27 pages, 3178 KB  
Review
The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders
by Ekaterina V. Marilovtseva, Amal Abdurazakov, Artemiy O. Kurishev, Vera A. Mikhailova and Vera E. Golimbet
Int. J. Mol. Sci. 2025, 26(19), 9492; https://doi.org/10.3390/ijms26199492 - 28 Sep 2025
Viewed by 633
Abstract
γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), regulates neuronal excitability, synaptic plasticity, and oscillatory activity essential for cognition, emotion, and behavior. Disruptions in GABAergic signaling are increasingly recognized as key contributors to a range of neurodevelopmental disorders [...] Read more.
γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), regulates neuronal excitability, synaptic plasticity, and oscillatory activity essential for cognition, emotion, and behavior. Disruptions in GABAergic signaling are increasingly recognized as key contributors to a range of neurodevelopmental disorders (NDDs), including schizophrenia (SZ), autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and intellectual disability (ID). In this review, we analyze the data available from the literature concerning the components of the GABA pathway. We describe the main steps of GABA metabolism, including GABA synthesis and release, GABA receptors neurotransmission, GABA reuptake and catabolism, and evaluate their involvement in the pathogenesis of neurodevelopmental disorders. We suggest the possibility of existence of so far undescribed mechanisms which maintain the concentrations of GABA at a relatively physiological level when the function of glutamic acid decarboxylases is compromised by mutations. Searching for these mechanisms could be important for better understanding neurodevelopment and could give a clue for future searches for new therapeutic approaches for treating or alleviating the symptoms of BD and SZ. We also argue that the metabolic stage of the GABA pathway has only a minor direct effect on GABA signaling and rather causes clinical effects due to accumulation of neurotoxic byproducts. Full article
(This article belongs to the Special Issue Molecular Investigations in Neurodevelopmental Disorders)
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30 pages, 3375 KB  
Article
Pro-Inflammatory Protein PSCA Is Upregulated in Neurological Diseases and Targets β2-Subunit-Containing nAChRs
by Mikhail A. Shulepko, Yuqi Che, Alexander S. Paramonov, Milita V. Kocharovskaya, Dmitrii S. Kulbatskii, Anisia A. Ivanova, Anton O. Chugunov, Maxim L. Bychkov, Artem V. Kirichenko, Zakhar O. Shenkarev, Mikhail P. Kirpichnikov and Ekaterina N. Lyukmanova
Biomolecules 2025, 15(10), 1381; https://doi.org/10.3390/biom15101381 - 28 Sep 2025
Viewed by 299
Abstract
Prostate stem cell antigen (PSCA) is a Ly6/uPAR protein that targets neuronal nicotinic acetylcholine receptors (nAChRs). It exists in membrane-tethered and soluble forms, with the latter upregulated in Alzheimer’s disease. We hypothesize that PSCA may be linked to a wider spectrum of neurological [...] Read more.
Prostate stem cell antigen (PSCA) is a Ly6/uPAR protein that targets neuronal nicotinic acetylcholine receptors (nAChRs). It exists in membrane-tethered and soluble forms, with the latter upregulated in Alzheimer’s disease. We hypothesize that PSCA may be linked to a wider spectrum of neurological diseases and could induce neuroinflammation. Indeed, PSCA expression is significantly upregulated in the brain of patients with multiple sclerosis, Huntington’s disease, Down syndrome, bipolar disorder, and HIV-associated dementia. To investigate PSCA’s structure, pharmacology, and inflammatory function, we produced a correctly folded water-soluble recombinant analog (ws-PSCA). In primary hippocampal neurons and astrocytes, ws-PSCA differently regulates secretion of inflammatory factors and adhesion molecules and induces pro-inflammatory responses by increasing TNFβ secretion. Heteronuclear NMR and 15N relaxation measurements reveal a classical β-structural three-finger fold with conformationally disordered loops II and III. Positive charge clustering on the molecular surface suggests the functional importance of ionic interactions by these loops. Electrophysiological studies in Xenopus oocytes point on ws-PSCA inhibition of α3β2-, high-, and low-sensitive variants of α4β2- (IC50 ~50, 27, and 15 μM, respectively) but not α4β4-nAChRs, suggesting targeting of the β2 subunit. Ensemble docking and molecular dynamics simulations predict PSCA binding to high-sensitive α4β2-nAChR at α4/β2 and β2/β2 interfaces. Complexes are stabilized by ionic and hydrogen bonds between PSCA’s loops II and III and the primary and complementary receptor subunits, including glycosyl groups. This study gives new structural and functional insights into PSCA’s interaction with molecular targets and provides clues to understand its role in the brain function and mental disorders. Full article
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14 pages, 5954 KB  
Article
Early Warning Technology for Heavy Metal Contaminant Leakage Based on Self-Potential Method
by Feng Wang, Hongli Li, Wei Zhang, Yansheng Liu, Guofu Wang and Xiaobo Jia
Water 2025, 17(19), 2839; https://doi.org/10.3390/w17192839 - 28 Sep 2025
Viewed by 265
Abstract
Heavy metal contamination poses significant environmental risks to groundwater and soil, necessitating efficient early-warning technologies for leakage detection. This study proposes a novel early-warning approach for heavy metal leakage using the self-potential (SP) method. A coupled numerical model integrating seepage, ion diffusion, and [...] Read more.
Heavy metal contamination poses significant environmental risks to groundwater and soil, necessitating efficient early-warning technologies for leakage detection. This study proposes a novel early-warning approach for heavy metal leakage using the self-potential (SP) method. A coupled numerical model integrating seepage, ion diffusion, and electric potential fields was developed within the COMSOL Multiphysics platform in order to elucidate the dynamic response mechanism of SP signals to advancing seepage fronts. Key findings reveal that the SP signal responds 1.5 h earlier than the contaminant diffusion front (Case 1), providing a critical early-warning window. The leakage process exhibits a distinct bipolar SP anomaly pattern (negative upstream/positive downstream), with the most significant response observed at the downstream toe area. Consequently, an optimized monitoring strategy prioritizing downstream deployment is proposed and validated using a representative landfill model. This SP-based technology offers a promising solution for real-time environmental risk monitoring, particularly in ecologically sensitive zones. Full article
(This article belongs to the Section Water Quality and Contamination)
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11 pages, 238 KB  
Article
Early-Onset and Delayed-Onset Postpartum Psychosis: A Case Series
by Júlia Olivé-Mas, Eva Aguilar, Meritxell Tost, Laia Martí, Cristina Giménez, Cristina Lesmes, Ana Moreno-Baró, Mariona Aparicio, Mireia Agut, Irina Olasz and Jesus Cobo
Women 2025, 5(4), 36; https://doi.org/10.3390/women5040036 - 28 Sep 2025
Viewed by 403
Abstract
Postpartum psychosis (PPP) is a rare but high-risk psychiatric emergency, with an estimated incidence of 1–2 in 1000 births. This study focuses on describing the characteristics of episodes occurring within the first postpartum year, specifically examining clinical, etiopathogenic, and prognostic differences between immediate- [...] Read more.
Postpartum psychosis (PPP) is a rare but high-risk psychiatric emergency, with an estimated incidence of 1–2 in 1000 births. This study focuses on describing the characteristics of episodes occurring within the first postpartum year, specifically examining clinical, etiopathogenic, and prognostic differences between immediate- or early-onset PPP (≤15 days postpartum) and delayed-onset PPP (onset after several weeks). Data were collected from ten patients diagnosed with PPP during the first postpartum year, and a retrospective descriptive analysis was conducted. Five patients experienced immediate or early decompensation and five experienced delayed onset. None of the variables analyzed showed a significant association with the timing of decompensation (p > 0.05). The majority of deliveries were vaginal (n = 8), and most patients were primiparous (n = 9). The most frequent subsequent diagnosis was schizophrenia or a psychotic spectrum disorder (n = 6). The type of partner showed a non-significant trend (p = 0.15), which may warrant further investigation. Notably, the role of partner type deserves closer examination, as it may act as a protective factor against the development of mental disorders and could inform targeted support strategies within health care systems. The lack of descriptions of time to onset periods (staging) in PPP samples could be a gap in the literature. Full article
22 pages, 1278 KB  
Review
Artificial Intelligence-Based Methods and Omics for Mental Illness Diagnosis: A Review
by Glenda Santos de Oliveira, Fábio Henrique dos Santos Rodrigues, João Guilherme de Moraes Pontes and Ljubica Tasic
Bioengineering 2025, 12(10), 1039; https://doi.org/10.3390/bioengineering12101039 - 27 Sep 2025
Viewed by 697
Abstract
The underlying causes fof major mental illnesses, including anxiety disorders (ADs), depression, and bipolar disorder (BD), remain insufficiently understood, limiting the availability of effective, patient-friendly treatments and accurate diagnostic tests. For instance, anxiety disorders encompass a diverse spectrum of subtypes and may emerge [...] Read more.
The underlying causes fof major mental illnesses, including anxiety disorders (ADs), depression, and bipolar disorder (BD), remain insufficiently understood, limiting the availability of effective, patient-friendly treatments and accurate diagnostic tests. For instance, anxiety disorders encompass a diverse spectrum of subtypes and may emerge at different stages of mental illness, each with distinct symptom profiles. This heterogeneity often complicates differential diagnosis, leading, in many cases, to delayed treatment or inappropriate management. In recent years, technological advances have enabled the development of artificial intelligence (AI)-based approaches that, when integrated with multi-omics data, offer substantial advantages over traditional statistical methods, particularly for analysing large-scale datasets and integrating clinical with bioanalytical information. This review analyses current efforts to identify biomarkers for mental illness and explores the application of machine learning, deep learning, and computational modelling in advancing personalised and precise diagnostics. Full article
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14 pages, 10382 KB  
Article
A Low-Power, Wide-DR PPG Readout IC with VCO-Based Quantizer Embedded in Photodiode Driver Circuits
by Haejun Noh, Woojin Kim, Yongkwon Kim, Seok-Tae Koh and Hyuntak Jeon
Electronics 2025, 14(19), 3834; https://doi.org/10.3390/electronics14193834 - 27 Sep 2025
Viewed by 253
Abstract
This work presents a low-power photoplethysmography (PPG) readout integrated circuit (IC) that achieves a wide dynamic range (DR) through the direct integration of a voltage-controlled oscillator (VCO)-based quantizer into the photodiode driver. Conventional PPG readout circuits rely on either transimpedance amplifier (TIA) or [...] Read more.
This work presents a low-power photoplethysmography (PPG) readout integrated circuit (IC) that achieves a wide dynamic range (DR) through the direct integration of a voltage-controlled oscillator (VCO)-based quantizer into the photodiode driver. Conventional PPG readout circuits rely on either transimpedance amplifier (TIA) or light-to-digital converter (LDC) topologies, both of which require auxiliary DC suppression loops. These additional loops not only raise power consumption but also limit the achievable DR. The proposed design eliminates the need for such circuits by embedding a linear regulator with a mirroring scale calibrator and a time-domain quantizer. The quantizer provides first-order noise shaping, enabling accurate extraction of the AC PPG signal while the regulator directly handles the large DC current component. Post-layout simulations show that the proposed readout achieves a signal-to-noise-and-distortion ratio (SNDR) of 40.0 dB at 10 µA DC current while consuming only 0.80 µW from a 2.5 V supply. The circuit demonstrates excellent stability across process–voltage–temperature (PVT) corners and maintains high accuracy over a wide DC current range. These features, combined with a compact silicon area of 0.725 mm2 using TSMC 250 nm bipolar–CMOS–DMOS (BCD) process, make the proposed IC an attractive candidate for next-generation wearable and biomedical sensing platforms. Full article
(This article belongs to the Special Issue CMOS Integrated Circuits Design)
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15 pages, 944 KB  
Article
Disentangling the Effects of Suicide Attempts and Psychiatric Diagnosis Based on a Genotype-Informed Dynamic Model of the Serotonin Presynapse
by Lana Radenković, Maja Pantović-Stefanović, Goran Brajušković, Maja Ivković, Dušanka Savić-Pavićević and Jovan Pešović
Genes 2025, 16(10), 1141; https://doi.org/10.3390/genes16101141 - 26 Sep 2025
Viewed by 282
Abstract
Background: Suicide attempts often co-occur with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCH). Although impairments of the serotonin (5-HT) system have been associated with suicide attempts, it remains unclear whether these alterations reflect suicidal behavior or are confounded by underlying [...] Read more.
Background: Suicide attempts often co-occur with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCH). Although impairments of the serotonin (5-HT) system have been associated with suicide attempts, it remains unclear whether these alterations reflect suicidal behavior or are confounded by underlying psychiatric diagnosis. This study used a genotype-informed dynamic model of the 5-HT presynapse to disentangle the effects of suicide attempts and psychiatric diagnosis. Methods: We applied a personalized dynamic model of the 5-HT presynapse to 392 psychiatric patients (with BD, MDD, or SCH), categorized by suicide attempt status, and 140 unaffected individuals. The model incorporated five variants across TPH2, SLC6A4, and MAOA genes simulating individual-specific concentration changes of five 5-HT-related molecular species. Model outputs were summarized by six statistical measures (mean, median, maximum, standard deviation, skewness, and kurtosis) and compared across groups. Results: No significant differences were found across groups defined by suicide attempt status and unaffected individuals. However, diagnosis significantly influenced 5-hydroxyindoleacetic acid (5-HIAA) mean, median, maximum, and standard deviation (all p < 0.05). BD patients had lower 5-HIAA levels than SCH patients (mean: p = 0.013; median: p = 0.013; maximum: p = 0.014; standard deviation: p = 0.014). MDD patients also showed lower 5-HIAA levels than SCH patients for the same measures, with differences approaching significance. No significant difference was observed between BD and MDD patients. A diagnosis-by-suicide attempt status interaction was observed for 5-HIAA skewness (p = 0.013). Conclusions: Model-derived 5-HT profiles were shaped primarily by diagnosis, while temporal dynamics of 5-HIAA, rather than its absolute levels, was associated with suicide attempt status. Thus, personalized dynamic modeling incorporating genetic variants may aid in detecting subtle molecular signatures across diagnoses and suicidal behavior. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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18 pages, 1558 KB  
Article
Oral Microbiota Taxa and Pri-miRNA Expression in Bipolar Disorder: A Case–Control Study
by Diego Primavera, Mauro Giovanni Carta, Massimo Tusconi, Goce Kalcev, Laura Atzori, Caterina Ferreli, Rober Romero Ramirez, Letizia Peddio, Cinzia Casu, Sara Fais, Germano Orrù and Alessandra Scano
Biomolecules 2025, 15(10), 1355; https://doi.org/10.3390/biom15101355 - 24 Sep 2025
Viewed by 398
Abstract
Background/Objectives: Emerging evidence suggests a role for oral microbiota in mood disorders, particularly bipolar disorder (BD), complementing established links between gut dysbiosis and psychiatric symptoms. This study investigates the composition of oral microbial taxa and the expression of inflammation-related pri-miRNAs (146a and 155) [...] Read more.
Background/Objectives: Emerging evidence suggests a role for oral microbiota in mood disorders, particularly bipolar disorder (BD), complementing established links between gut dysbiosis and psychiatric symptoms. This study investigates the composition of oral microbial taxa and the expression of inflammation-related pri-miRNAs (146a and 155) in individuals with BD, aiming to explore their potential as biomarkers in the oral–gut–brain axis. Methods: A matched case–control design was implemented, recruiting 25 BD patients and 46 controls matched by age and sex. Salivary samples were collected, and microbial profiling was conducted via real-time qPCR targeting major bacterial phyla and genera. Pri-miRNA 146a and 155 expression was evaluated through RT-qPCR using validated primers. Statistical comparisons between groups were performed using Fisher’s exact test and non-parametric tests for continuous variables. Results: Microbial analysis revealed significant reductions (p < 0.01) in α-Proteobacteria, γ-Proteobacteria, and Actinobacteria in BD patients versus controls. A shift toward a higher Firmicutes/Bacteroidetes ratio was observed in the BD cohort, suggesting differences in the oral biotic status between the two groups. However, pri-miRNA 146a and 155 expression levels did not differ significantly between the groups and exhibited high inter-individual variability. Conclusions: The findings indicate that oral microbiota composition differs in BD patients, potentially influencing systemic homeostasis through interactions with gut microbial communities and SCFA pathways. These findings should be interpreted as preliminary and hypothesis-generating given the modest sample size. While pri-miRNAs 146a and 155 did not distinguish BD status, the observed microbial taxa alterations should be regarded as exploratory and hypothesis-generating. Larger, longitudinal studies are required to clarify their potential role in BD pathogenesis and risk assessment. Full article
(This article belongs to the Special Issue Biomarkers and Molecular Basis of Psychiatry)
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11 pages, 796 KB  
Article
Unveiling the Interplay of EBV, HSV-1, and Inflammatory Biomarkers in Psychiatric Disorders
by Özer Akgül, Ömer Faruk Demirel, İlker Tosun, Yasin Kavla, Mehmet Murat Kirpinar, Burcu Sapmaz, Gülçin Şenyiğit, Reyhan Çalişkan and Yaşar Ali Öner
J. Clin. Med. 2025, 14(19), 6730; https://doi.org/10.3390/jcm14196730 - 24 Sep 2025
Viewed by 325
Abstract
Background/Objectives: Schizophrenia (SCH), bipolar disorder (BPD), and major depressive disorder (MDD) are increasingly viewed as neuroimmune disorders shaped by viral exposure and inflammation. Disorder-specific immunovirological profiles, however, remain poorly defined. Methods: In this cross-sectional study, we assessed Epstein–Barr Virus (EBV) and Herpes Simplex [...] Read more.
Background/Objectives: Schizophrenia (SCH), bipolar disorder (BPD), and major depressive disorder (MDD) are increasingly viewed as neuroimmune disorders shaped by viral exposure and inflammation. Disorder-specific immunovirological profiles, however, remain poorly defined. Methods: In this cross-sectional study, we assessed Epstein–Barr Virus (EBV) and Herpes Simplex Virus type 1 (HSV-1) seropositivity and measured serum CRP, IL-6, and IL-1β in 708 participants: 110 with SCH, 121 with BPD, 135 with MDD, and 342 healthy controls (HC). Statistical analyses included Shapiro–Wilk tests for normality; Kruskal–Wallis with Bonferroni-adjusted Dunn post hoc comparisons; and logistic regression adjusted for age, sex, and marital status. Results: EBV seropositivity was higher in SCH (90.9%) than in HC (78.9%) (OR = 3.46, 95% CI: 1.68–7.12; p = 0.001) but not in BPD or MDD. HSV-1 seropositivity was elevated in BPD (83.5%) versus HC (67.0%) (OR = 2.29, 95% CI: 1.34–3.92; p = 0.003), with no differences in SCH or MDD. Inflammatory biomarkers were significantly increased in SCH and MDD compared to HC (p < 0.001), while BPD showed no differences. Conclusions: The findings delineate distinct immunovirological patterns across major psychiatric disorders. Schizophrenia was characterized by EBV seropositivity accompanied by systemic inflammatory activation, bipolar disorder by HSV-1 seropositivity in the absence of inflammatory changes, and major depressive disorder by inflammatory dysregulation independent of viral exposure. These disorder-specific profiles highlight heterogeneity in neuroimmune pathways and underscore the potential relevance of biomarker-based stratification for generating hypotheses regarding targeted antiviral or anti-inflammatory interventions in psychiatric populations. Full article
(This article belongs to the Section Mental Health)
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21 pages, 3073 KB  
Article
Treatment of Na2SO4-Containing Wastewater Generated During the Recycling of Spent Lithium-Ion Batteries: Comparative Study on the Operating Modes of Bipolar Membrane Electro-Dialysis
by Minhyuk Seo, Youngjae Lee, Junhee Kim, Jaehyuk Chang, Yeonchul Cho and Jaewoo Ahn
Metals 2025, 15(10), 1067; https://doi.org/10.3390/met15101067 - 23 Sep 2025
Viewed by 369
Abstract
The recycling of spent lithium-ion batteries generates Na2SO4-containing wastewater, resulting in environmental problems and resource losses. This study investigates a treatment method employing bipolar membrane electrodialysis (BMED) to recover H2SO4 and NaOH from such wastewater. The [...] Read more.
The recycling of spent lithium-ion batteries generates Na2SO4-containing wastewater, resulting in environmental problems and resource losses. This study investigates a treatment method employing bipolar membrane electrodialysis (BMED) to recover H2SO4 and NaOH from such wastewater. The acid and base recovery efficiencies, energy consumption, operational stability, and economic feasibility of two BMED configurations, i.e., two- and three-compartment systems, were systematically compared. The current density, initial concentrations of the feed, and initial concentrations and volumes of the acid and base were optimized under constant current conditions. The three-compartment system exhibited higher acid purity and stability, whereas the other system exhibited lower energy consumption and membrane degradation. Under optimal conditions, both systems successfully recovered H2SO4 and NaOH from the Na2SO4-containing wastewater. A techno-economic analysis based on a lab-scale process revealed that the two-compartment system exhibited cost effectiveness while the three-compartment system showed long-term operational stability. These findings suggest that BMED is a viable and effective solution for the treatment of Na2SO4-containing wastewater generated from battery recycling processes. Full article
(This article belongs to the Special Issue Advances in Mineral Processing and Hydrometallurgy—3rd Edition)
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24 pages, 6230 KB  
Article
Genetic Loss of VGLUT1 Alters Histogenesis of Retinal Glutamatergic Cells and Reveals Dynamic Expression of VGLUT2 in Cones
by Sriparna Majumdar and Vincent Wu
Brain Sci. 2025, 15(9), 1024; https://doi.org/10.3390/brainsci15091024 - 22 Sep 2025
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Abstract
Background/Objectives: Glutamatergic neurotransmission is essential for the normal functioning of the retina. Photoreceptor to bipolar and bipolar to ganglion cell signaling is mediated by L-glutamate, which is stored in and released from vesicular glutamate transporter 1 (VGLUT1) containing synaptic vesicles. VGLUT1 is [...] Read more.
Background/Objectives: Glutamatergic neurotransmission is essential for the normal functioning of the retina. Photoreceptor to bipolar and bipolar to ganglion cell signaling is mediated by L-glutamate, which is stored in and released from vesicular glutamate transporter 1 (VGLUT1) containing synaptic vesicles. VGLUT1 is expressed postnatally, P2 onwards, and is required for the glutamatergic retinal wave observed between P10 and P12 in the developing mouse retina. P9–P13 postnatal age is critical for retinal development as VGLUT1 expressing ribbon synapses activate in the outer and inner plexiform layers, and rod/cone mediated visual signaling commences in that period. Although it has been hypothesized that glutamatergic extrinsic signaling drives cell cycle exit and initiates cellular differentiation in the developing retina, it is not clear whether intracellular, synaptic, or extrasynaptic vesicular glutamate release contributes to this process. Recent studies have attempted to decipher VGLUT’s role in retinal development. Here, we investigate the potential effect of genetic loss of VGLUT1 on early postnatal histogenesis and development of retinal neural circuitry. Methods: We employed immunohistochemistry and electrophysiology to ascertain the density of glutamatergic, cholinergic, and dopaminergic cells, spontaneous retinal activity, and light responses in VGLUT1 null retina, and contrasted them with wildtype (WT) and melanopsin null retina. Results: We have demonstrated here that VGLUT1 null retina shows signs of age dependent retinal degeneration, similar to other transgenic mice models with dysfunctional photoreceptor to bipolar cell synapses. The loss of VGLUT1 specifically alters glutamatergic cell density and morphological maturation of retinal ganglion cells. Moreover, VGLUT2 expression is lost in the majority of VGLUT2 cones in the absence of VGLUT1 coexpression, except when VGLUT2 coexpresses transiently with VGLUT3 in these cones, or when VGLUT1 null mice are dark reared. Conclusions: We present the first evidence that synaptic or extrasynaptic postnatal glutamate release from VGLUT1 containing vesicles impacts histogenesis of glutamatergic cells, pruning of retinal ganglion cell dendrites and VGLUT2 expression in cones. Full article
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