Search Results (2,579)

The oilfield gathering and transportation system (OGTS) accounts for a substantial share of total energy consumption, demonstrating considerable potential for energy-saving optimization. Previous research primarily focused on the independent optimization of gathering pipeline networks or processing stations, with little attention given to their integrated optimization. This study investigates the OGTS of a domestic oilfield block. It develops artificial neural network (ANN) surrogate models for both pipelines and processing station equipment to accurately capture system operating states. An optimization model linking the pipeline network and processing station is established, and a differential evolution algorithm is applied to enhance computational efficiency. The results indicate that optimal predictive performance was achieved when the first hidden layer of the backpropagation neural network (BPNN) contained 50 neurons with a rectified linear unit (ReLU) activation function, with the surrogate models achieving coefficient of determination (R²) values exceeding 0.85. Under a 30 min optimization cycle, total system energy consumption decreased by 2.28%, with computation completed in under 3 min, while daily average optimization led to a 1.55% reduction. These findings demonstrate that the proposed integrated optimization framework offers both a robust methodological foundation and practical engineering guidance for coordinated, low-carbon, and energy-efficient operation of oilfields. Full article

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by heterogeneous behavioral symptoms and systemic comorbidities, including immune and gastrointestinal dysfunctions. Emerging studies suggest that glycosylation—a fundamental post-translational modification regulating cellular communication and immune responses—may play a role in ASD pathophysiology, yet its contribution remains underexplored. Methods: In this study, we developed an integrative transcriptomic and network analysis framework to investigate glycosylation-related gene expression changes and their functional associations in ASD. Using publicly available datasets from bulk and single-cell RNA sequencing of brain and blood tissues, we focused on four prior-knowledge gene subsets: glycogenes, extracellular matrix glycoproteins, immune response genes, and autism risk genes. Results: Differential expression and pathway enrichment analyses revealed consistent dysregulation of glycosylation pathways, including mucin-type O-glycan biosynthesis, glycosaminoglycan metabolism, GPI-anchor formation, and sialylation, across ASD tissues. These transcriptional changes were functionally linked to altered immune signaling (e.g., IL-17, Toll-like receptor, and complement pathways) and synaptic development pathways, forming a distinct glyco-immune axis. Network analysis identified key glycogenes such as GALNT10, NEU1, LMAN2L, and CHST1 as central molecular nodes, interacting with immune and neuronal regulators. Linkage disequilibrium analysis further revealed ASD-associated SNPs influencing the expression of these glycogenes in both blood and brain tissues. Conclusions: Together, these findings support a model in which disrupted glycosylation contributes to ASD pathophysiology by mediating immune dysregulation and altered neuronal connectivity. This study offers a systems-level framework to understand the molecular complexity of ASD and highlights glycogenes as potential biomarkers and targets for future therapeutic exploration. Full article

Introduction: Pathogenic mutations in leucine-rich repeat protein kinase-2 (LRRK2), particularly G2019S, constitute the most common cause of autosomal dominant PD. Methods: Mouse models encoding human mutant alpha-synuclein (SNCA A53T) and LRRK2 G2019S were treated with a brain-penetrant kinase inhibitor (BK40196). Behavior, nigrostriatal and mesolimbic dopamine (DA) pathways were examined. Results: Mice harboring LRRK2 G2019S do not show age-dependent motor symptoms, but mice encoding SNCA A53T display motor deficits, while both strains exhibit anxiety-like behavior and BK40196 improves motor and behavioral defects. BK40196, a multi-kinase inhibitor of Abelson (Abl), Discoidin domain receptor (DDR)-1, c-KIT and FYN, alters microglial morphology and alpha-synuclein levels in SNCA A53T mice and improves DA neurotransmission, primarily via the nigrostriatal system. BK40196 inhibits brain LRRK2 G2019S (IC₅₀ of 89nM) and does not affect phosphorylated or total peripheral LRRK2 levels (lungs, kidneys, liver, etc.). LRRK2 G2019S mice treated with BK40196 exhibit distinct increases in DA in mesolimbic neurons such as the nucleus accumbens (NAcc), suggesting differential mechanisms of DA neurotransmission in mutant alpha-synuclein and LRRK2 models of PD. Conclusions: LRRK2 G2019S may primarily involve mesolimbic pathways leading to nonmotor symptoms independent of the motor and behavioral manifestations associated with alpha-synuclein via the nigrostriatal system. BK40196 may provide a comprehensive and synergistic therapeutic approach that addresses multiple mechanisms to reduce the pathologies related to LRRK2 G2019S and/or SNCA in PD. The multiple pathologies of PD necessitate a holistic approach that simultaneously targets inflammation and autophagy and LRRK2 inhibition. Full article

The capacity of the brain to adapt to experience has long been associated with synaptic plasticity; however, recent evidence demonstrates that experience-driven neural activity also modulates white matter organization through dynamic regulation of oligodendrocyte lineage cells and myelination. Activity-dependent myelination has emerged as a complementary form of neuroplasticity that contributes to circuit efficiency, temporal coordination, and cognitive function. This review aims to examine the neurobiological mechanisms linking cognitive stimulation and activity-dependent neuronal signaling with oligodendroglial dynamics and adaptive myelination. A narrative review of experimental and translational studies was conducted, focusing on evidence from animal models and human research exploring neuron–oligodendroglia interactions, neurotransmitter-mediated signaling, learning paradigms, physical exercise, and neuromodulatory interventions relevant to myelination and brain plasticity. Accumulating evidence indicates that cognitive stimulation, learning, and physical activity modulate neuronal firing patterns and neurotransmitter release, influencing oligodendrocyte precursor cell proliferation, differentiation, and myelin remodeling. Neurotransmitters such as glutamate, GABA, dopamine, and acetylcholine play key roles in neuron–oligodendroglia communication, largely through calcium-dependent intracellular signaling pathways. These mechanisms have been associated with experience-dependent circuit refinement across motor, cognitive, and stress-related paradigms. Rather than implying direct clinical effects, this review highlights oligodendroglial plasticity as a biologically plausible substrate through which cognitive and behavioral experiences may influence adaptive myelination and white matter integrity. Understanding these mechanisms provides a conceptual framework for future research exploring non-pharmacological approaches to modulate brain plasticity at the level of myelin. Full article

Land cover classification (LCC) is a fundamental task in remote sensing, which enables effective environmental monitoring, agricultural planning, and disaster management. The existing approaches often rely on fine-tuning pre-trained models, which are not specifically designed for LCC, which lead to suboptimal performance in complex scenarios. To address these limitations, we propose the Cross-Module Attention Land Cover Network (CALCNet), a novel architecture developed from scratch. CALCNet follows a contracting and restoration backbone, where the contracting path extracts progressively abstract semantic features while reducing spatial resolution, and the restoration path recovers fine-grained spatial details through upsampling and skip connections. In addition, CALCNet integrates a cross-module attention mechanism that combines spatial attention and multi-scale feature selection to enhance feature representation. Furthermore, we applied a differential evolution-based neuron pruning strategy to create a compressed CALCNet variant, which retains high classification performance while reducing computational cost. The CALCNet is evaluated on four benchmark LCC datasets, AID, UCMerced_LandUse, NWPU_RESISC45, and EuroSAT, demonstrating strong performance across all benchmarks. Specifically, the model achieves classification accuracies of 98.09%, 99.47%, 99.19%, and 99.19%, respectively. The compressed CALCNet variant reduces computational cost to 78.55 million floating point operations (FLOPs) with a model size of 43 MB, while achieving improved inference speeds (38.32 frames/sec on CPU and 118.3 frames/sec on GPU), representing approximately 45–50% reduction in FLOPs and model storage. These results highlight that CALCNet is both highly accurate and computationally efficient, making it well suited for real-world LCC applications. Full article

Ischemic stroke induces complex molecular responses that disrupt subcellular organelles’ function and contribute to brain injury, yet the temporal changes of organelle-specific transcriptomic remodeling remain to be investigated. In this study, we performed in silico analysis of publicly available transcriptomic data from isolated brain microvessels of transient middle cerebral artery occlusion (tMCAO) mouse model. Using in silico approaches, we analyzed differential gene expression at 24 h (acute phase) and 7 d (intermediate phase) post-stroke, focusing on mitochondria, endoplasmic reticulum (ER), and Golgi apparatus. Functional enrichment (Gene Ontology, KEGG) and protein–protein interaction network analyses were performed. Our analysis of the data revealed that at 24 h post-stroke, all three organelles exhibited marked transcriptional remodeling, where mitochondrial pathways showed disrupted metabolic and redox regulation; ER pathways indicated activation of biosynthetic processes, stress signaling, and ferroptosis; and Golgi-related genes reflected altered vesicular trafficking and glycosylation. By 7 d, mitochondrial alterations subsided, whereas ER and Golgi pathways displayed downregulation of metabolic and neuronal signaling processes, indicating persistent dysfunction and incomplete microvascular recovery. Phase-specific drug–gene interaction analysis will be useful to understand temporal organelle-associated transcriptional organization and to guide future investigations of neurovascular remodeling after ischemic stroke. Full article

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection. Full article

Oligodendroglial cells are the myelinating glial cells of the central nervous system (CNS), and their morphological differentiation is a prerequisite for efficient myelin formation, which is essential for proper neuronal function. While oligodendroglial morphological changes normally proceed through tightly regulated developmental transitions, disruption of the underlying molecular mechanisms can lead to aberrant cellular phenotypes characterized by either premature, insufficient, or excessive differentiation. Although the phosphatidylinositol 3-kinase (PI3K) and its downstream Akt kinase signaling are well established as major drivers of oligodendrocyte morphological differentiation, myelination, and CNS white matter formation, how its negative regulator, phosphatase and tensin homolog (PTEN), is involved in the regulation of oligodendroglial morphogenesis remains incompletely understood. Recent genetic studies have highlighted a spectrum of disorders caused by PTEN dysfunction, conceptually established but currently evolving as PTENopathy, which has been partially associated with white matter abnormalities. Here, we report that, in an experimental model using the FBD-102b cell line, a well-established model of oligodendroglial cell differentiation, chemical inhibition of PTEN enhances pronounced morphological changes characterized by widespread membranes, accompanied by increased expression of differentiation and/or myelin marker proteins. We then focused on Rho family small GTPases, central regulators of cell morphogenesis, and examined their potential involvement downstream of this signaling. Expression of the RhoG-binding domain (RBD) of engulfment and cell motility 1 (ELMO1) attenuated the increased morphological changes. Similarly, inhibition of downstream Akt signaling also reversed these changes. Taken together, these results provide insight into how balanced regulation between PTEN and downstream signaling molecules governs oligodendroglial cell differentiation and suggest that dysregulation of this signaling equilibrium may contribute to cellular phenotypes relevant to disease-associated cellular alterations. Full article

Fetal hypoxia and maternal stress during pregnancy are major risk factors for neurological disorders. The effects of maternal hypoxia may be transmitted to the next generation through persistent alterations in maternal endocrine and metabolic regulation. In this study, using immunohistochemistry, quantitative RT-PCR, and Western blotting, we assessed morphological features and HIF1-dependent processes in the fetal and adult brains of progeny of female rats exposed to maternal hypoxia (PMH). We identified a delay in progenitor cell differentiation into neurons at embryonic day 14, a decreased number of neurons in the hippocampus, an increased number of astrocytes in the prefrontal cortex, and a decreased number of astrocytes in the raphe nuclei of the PMH rats. However, no significant changes were observed in HIF1α protein levels or in the protein levels of HIF1-dependent gene products in the examined brain structures. Thus, the transgenerational effect of maternal hypoxia is manifested as structural disturbances of brain development but is not accompanied by changes in HIF1-dependent metabolism. Full article

Background/Objectives: Neuritogenesis and synaptogenesis support learning and cognitive function, and hippocampal neurons play central roles in these processes. Cleistocalyx nervosum var. paniala (CNP), a Southeast Asian berry, has reported neuroprotective activities, but its direct effects on hippocampal neurons remain unclear. We investigated whether CNP extract modulates hippocampal neuronal transcriptomes, neuritogenesis, and synaptogenesis. Methods: Primary hippocampal neurons isolated from male and female Wistar rat pups were treated with CNP extract in vitro. Cytotoxicity was assessed to define non-cytotoxic concentrations. Transcriptomic responses were profiled by RNA sequencing and validated by RT-qPCR. Neuritogenesis was quantified by neurite morphology and Sholl analysis. Synaptogenesis was evaluated by synaptic immunocytochemistry. Molecular docking of cyanidin-3-glucoside (C3G) and resveratrol was used to generate mechanistic hypotheses. Results: At 0.1–10 µg/mL, CNP was non-cytotoxic, whereas a 100 µg/mL dose reduced viability; therefore, 10 µg/mL was used in subsequent experiments. Exploratory RNA-seq profiling identified thousands of differentially expressed genes enriched in synapse- and neurite-related pathways, including synaptogenesis signaling, axon guidance, and neuritogenesis. RT-qPCR showed upregulation of Igf1 in males and Glul in females, with sex-dependent modulation of Bdnf and Cask. CNP increased neurite length, branching, and Sholl complexity in both sexes, with a more pronounced effect in males. A male-biased effect was also observed in synapse-related marker colocalization, with increased Syn1–Psd95 colocalization detected in males. Docking suggested plausible interactions of C3G and resveratrol with regulators such as MYC, TP53, and CREB1. Conclusions: CNP extract alters transcriptional networks and enhances neurite outgrowth in primary hippocampal neurons in a sex-dependent manner, with male-biased effects on Syn1–Psd95 colocalization. These findings support further dose–response, mechanistic, and sex-stratified in vivo studies to evaluate its neurobiological potential. Full article

Neurofilament light chain (NfL) is a promising biomarker of axonal injury across acute and chronic neurodegeneration, which can improve drug discovery and disease monitoring models. Traditional in vivo animal models cannot fully mimic human pathophysiology of neurodegenerative diseases (NDDs), but in vitro models based on human cells solve this problem, reducing the time and cost of drug testing. We developed an electrochemical immunosensor for NfL detection in cell culture media to monitor acute neuronal injury in in vitro models. The biosensor was designed in two configurations: the label-free system, which directly detects NfL in the sample via the antibody–antigen interaction, and the sandwich configuration, which incorporates two additional antibodies. Detection was examined using electrochemical techniques, including cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and chronoamperometry (CA). The sensor demonstrated a detection limit of 3–9 pg mL⁻¹, and a dynamic working range spanning from 10 up to 10⁷ pg mL⁻¹. Importantly, NfL was successfully detected in physiological media collected from cultured neurons that were differentiated from the long-term human neuroepithelial-like stem cells. This discovery highlights the platform’s applicability for in vitro neurodegenerative models. The immunosensor offers a sensitive, scalable, and cost-effective alternative for neurodegeneration detection in drug testing applications. Full article

The olfactory system plays a crucial role in mediating fish behaviour, including reproduction. Senegalese sole (Solea senegalensis) is an important aquaculture flatfish species in Europe, in which reproductive dysfunction in captive males has been linked to potential alterations in chemical communication. Despite the expanded repertoire of olfactory receptor genes described for this species, detailed information on the cellular organization of its olfactory organs remains limited. This study provides a comprehensive histological, immunohistochemical, lectin-histochemical, and ultrastructural characterization of the olfactory rosettes of S. senegalensis across multiple life stages, including premetamorphic larvae, fry, juveniles and adults. Although the olfactory organs undergo substantial structural changes following metamorphosis, differentiated and functionally active olfactory sensory neurons (OSNs) are already present in premetamorphic larvae. Subsequently, two epithelial regions were distinguished along the olfactory lamellae: a sensory epithelium containing abundant OSNs and supporting cells, and a nonsensory epithelium dominated by goblet and other secretory cells. Ciliated and microvillous OSNs were distinguished from 60 dph onward based on morphological and ultrastructural features and supported by immunoreactivity with CR, CB, Gγ8 and PGP. Crypt cells showed immunolabelling with S100, NSE and CYK8. Furthermore, lectin histochemistry revealed ontogenetic changes in epithelial glycoconjugates, with early diffuse binding patterns evolving into stratified and region-specific distributions. Overall, these results demonstrate the structural and functional complexity of the olfactory epithelium in S. senegalensis, significantly enriching the limited available morphological and neurochemical information on the species. Full article

The SH-SY5Y cell line is widely used as an in vitro model for pharmacological and molecular investigations of Parkinson’s disease (PD). The use of SH-SY5Y cells in PD research critically relies on their ability to differentiate into a mature, post-mitotic, dopaminergic (DAergic) neuronal phenotype. However, SH-SY5Y cells are inherently heterogeneous since they are firstly catecholaminergic cells and may express diverse phenotypic markers besides the DAergic ones. These properties seem to be determined by the differentiation protocol that is employed, thus meaning it is crucial to obtain proper cell types. This systematic review aims to discuss the main differentiation protocols used in PD research over the last 30 years. They include inducers such as retinoic acid (RA), the phorbol ester TPA, and the BDNF. Among the 514 studies that were screened, 249 employed these inducers. Then, we quantitatively report the ability of these protocols to differentiate SH-SY5Y cells in mature DAergic neurons, evaluating morphology, differentiation markers, and DAergic markers among the studies that specifically compared differentiated to undifferentiated SH-SY5Y cells (61 studies over 249). As our research shows, despite the highest usage of the RA differentiation protocol, the combination of RA with the BDNF inducer seems to increase the expression and the acquisition of a DAergic phenotype. Nevertheless, during this analysis, some limitations emerged, highlighting the intrinsic phenotypic heterogeneity of these cells, thereby limiting their suitability according to the specific biological question under investigation. A deep investigation into the literature about the molecular phenotypic features of differentiated SH-SY5Y cells may eventually help us to understand the advantages and disadvantages of each protocol that was employed, and adequately set experiments around the PD research. Full article

Animal studies have shown that early life exposure to general anesthetics may impair brain development. However, the implications of this phenomenon in human patients remain unclear. In this study, we use an induced pluripotent stem cell (iPSC)-derived human brain microphysiological system (bMPS) to investigate the effects of early sevoflurane (SEV) exposure on human brain development. Human iPSCs were cultured and differentiated into neural progenitor cells (NPCs) and then into bMPS. At week 8, bMPSs were exposed to 2.4% SEV for 4 h. Four weeks after exposure, immunofluorescence (IF), Western blotting (WB), and quantitative real-time polymerase chain reaction (qPCR) were conducted to evaluate the alteration of nerve cells in bMPS. After SEV exposure, the number of apoptotic cells increases, and the level of neural differentiation markers decreases. The ratios of mature neurons over NPCs and mature oligodendrocytes over oligodendrocyte progenitor cells (OPCs) are reduced, which leads to a reduction in myelination. SEV also impedes the development of astrocytes and synaptogenesis, especially the formation of excitatory synapses. Meanwhile, SEV increases the expression of molecules in the mammalian target of rapamycin (mTOR) signal pathway. In conclusion, early SEV exposure substantially disrupts the development of human brain tissue, and the mTOR signal pathway is likely to be involved in this alteration. Full article

Bisphenol A (BPA) has long been used in plastics, resins, and food packaging materials; however, extensive research has demonstrated its reproductive, developmental, and endocrine-disrupting effects. Consequently, BPA has been increasingly restricted and replaced with structural analogues. Among these, tetramethyl bisphenol F (TMBPF) has emerged as one of the most widely used substitutes, particularly in epoxy resins and food-can coatings. Although initially regarded as a safer alternative, accumulating evidence suggests that TMBPF may exert multiple toxicological effects, raising concerns about its potential developmental neurotoxicity. The present study aimed to investigate the neurodevelopmental effects of TMBPF using both in vitro and in vivo approaches. First, a developmental neurotoxicity assay employing Sox1−GFP mouse embryonic stem cells was used to evaluate cytotoxicity using the cell counting kit-8 assay and neural differentiation based on green fluorescent protein (GFP) fluorescence intensity. The results indicated developmental neurotoxic potential according to the established discrimination index. Subsequently, pregnant and lactating mice were exposed to TMBPF daily from gestational day 10.5 to postnatal day 20, and their offspring were assessed for behavioral performance as well as changes in the expression of neurodevelopment-related genes in the brain. Behavioral analyses encompassed multiple domains, including memory and learning, social behavior, anxiety-related responses, and spontaneous locomotor activity, suggesting alterations in these functional outcomes. Molecular analyses further demonstrated changes associated with dopaminergic and cholinergic signaling, synaptic plasticity, neuronal activity markers, neuropeptides, and inflammatory pathways. Collectively, these findings provide the first evidence in a mammalian model that maternal exposure to TMBPF may influence offspring neurodevelopment. These findings suggest potential implications for human exposure to TMBPF, particularly through food-contact materials, and warrant further mechanistic and dose–response studies. Full article