Ebastine-mediated destabilization of E3 ligase MKRN1 protects against metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer.

Multimodal cross-scale context clusters for classification of mental disorders using functional and structural MRI.

The brain is a complex system with multiple scales and hierarchies, making it challenging to identify abnormalities in individuals with mental disorders. The dynamic segregation and integration of activities across brain regions enable flexible switching between local and global information processing modes. Modeling these scale dynamics within and between brain regions can uncover hidden correlates of brain structure and function in mental disorders.

Non-saponin from maintains blood-brain barrier integrity by inhibiting NF-κB and p38 MAP kinase signaling pathways to prevent the progression of experimental autoimmune encephalomyelitis.

Background: The non-saponin (NS) fraction is an important active component of with multifunctional pharmacological activities including neuroprotective, immune regulatory, anti-inflammatory, and antioxidant effects. However, the effects of NSs on multiple sclerosis (MS), a chronic and autoimmune demyelinating disorder, have not yet been demonstrated.

Purpose: and Methods: The goal of the present study was to demonstrate the pharmacological actions of NSs on movement dysfunctions and the related mechanisms of action using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.

Aberrant Structural-Functional Coupling of Large-Scale Brain Networks in Older Women With Subthreshold Depression.

Objectives: Subthreshold depression (SD) is common in the older population, more so in females than males, and can lead to serious physical and mental ill-health. However, the underlying neurobiology remains unclear. This study used multimodal magnetic resonance imaging (MRI) to investigate the topological organization and coupling of the structural and functional brain networks in older women with SD.

A microglial kinase ITK mediating neuroinflammation and behavioral deficits in traumatic brain injury.

Microglia-mediated neuroinflammation has been implicated in the neuropathology of traumatic brain injuries (TBI). Recently, the expression of interleukin-2-inducible T-cell kinase (ITK) has been detected in brain microglia, regulating their inflammatory activities. However, the role of microglial ITK in TBI has not been investigated.

Disturbed hierarchy and mediation in reward-related circuits in depression.

Backgrounds/objective: Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation.

Methods: Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N = 52) and demographically matched healthy controls (N = 60).

Learning Dendritic-Neuron-Based Motion Detection for RGB Images: A Biomimetic Approach.

In this study, we designed a biomimetic artificial visual system (AVS) inspired by biological visual system that can process RGB images. Our approach begins by mimicking the photoreceptor cone cells to simulate the initial input processing followed by a learnable dendritic neuron model to replicate ganglion cells that integrate outputs from bipolar and horizontal cell simulations. To handle multi-channel integration, we utilize a nonlearnable dendritic neuron model to simulate the lateral geniculate nucleus (LGN), which consolidates outputs across color channels, an essential function in biological multi-channel processing.

Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution.

Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems, yet their impact on zebrafish ( ) embryonic development, particularly erythropoiesis, remains underexplored. This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos. validation experiments corroborated the transcriptomic findings, revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation, as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.

Amygdala-centered fusional connections characterized nonmotor symptoms in Parkinson's disease.

The importance of nonmotor symptoms in understanding the pathogenesis of the heterogeneity of Parkinson's disease has been highlighted. However, the validation of specific brain network biomarkers in nonmotor symptom subtypes is currently lacking. By performing a new approach to compute functional connectivity with structural prior using magnetic resonance imaging, the present study computed both functional connectivity and fusional connectivity features in the nonmotor symptom subtypes of Parkinson's disease, one characterized by cognitive impairment with late onset and the other depression with early onset.

Key regions aberrantly connected within cerebello-thalamo-cortical circuit and their genetic mechanism in schizophrenia: an fMRI meta-analysis and transcriptome study.

Recent studies have showed aberrant connectivity of cerebello-thalamo-cortical circuit (CTCC) in schizophrenia (SCZ), which might be a heritable trait. However, these individual studies vary greatly in their methods and findings, and important areas within CTCC and related genetic mechanism are unclear. We searched for consistent regions of circuit dysfunction using a functional magnetic resonance imaging (fMRI) meta-analysis, followed by meta-regression and functional annotation analysis.

The pharmacodynamic modulation effect of oxytocin on resting state functional connectivity network topology.

Introduction: Neuroimaging studies have demonstrated that intranasal oxytocin has extensive effects on the resting state functional connectivity of social and emotional processing networks and may have therapeutic potential. However, the extent to which intranasal oxytocin modulates functional connectivity network topology remains less explored, with inconsistent findings in the existing literature. To address this gap, we conducted an exploratory data-driven study.

How does oxytocin modulate human behavior?

While the highly evolutionarily conserved hypothalamic neuropeptide, oxytocin (OT) can influence cognitive, emotional and social functions, and may have therapeutic potential in disorders with social dysfunction, it is still unclear how it acts. Here, we review the most established findings in both animal model and human studies regarding stimuli which evoke OT release, its primary functional effects and the mechanisms whereby exogenous administration influences brain and behavior. We also review progress on whether OT administration can improve social symptoms in autism spectrum disorder and schizophrenia and consider possible impediments to translational success.

Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.

Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington's disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, we engineer the ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins to peroxisomes, to remove mHttex1 aggregates.

Neural underpinnings of a two-phase memory suppression process in the neural response to self-related and observed perspective views.

Individuals often actively suppress intrusive memories to alleviate the distress they cause and maintain mental well-being. However, those with post-traumatic stress disorder (PTSD) often exhibit difficulties particularly in inhibiting or suppressing negative memories compared to individuals without PTSD. These memories can involve a physical threat either to the individual themselves or to others.

SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.

Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures.

TWIK-1 belongs to the two-pore domain K (K2P) channel family, which plays an essential role in the background K conductance of cells. Despite the development of exon 2-deleted knockout (KO) mice, the physiological role of TWIK-1 has remained largely unknown. Here, we observed that the exon 2-deleted KO mice expressed an internally deleted TWIK-1 (TWIK-1 ΔEx2) protein, which unexpectedly acts as a functional K channel.

Radiopaque hydrogel-in-liposomes towards theranostic applications for malignant tumors.

A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction.

RNA dysregulation in neurodegenerative diseases.

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying RNA processing underscore the essential role of RNA regulation in maintaining neuronal health and function. RNA molecules are bound by RNA-binding proteins (RBPs), and interactions between RNAs and RBPs are commonly affected in neurodegeneration.

EBP1 potentiates amyloid β pathology by regulating γ-secretase.

The abnormal deposition of amyloid β (Aβ), produced by proteolytic cleavage events of amyloid precursor protein involving the protease γ-secretase and subsequent polymerization into amyloid plaques, plays a key role in the neuropathology of Alzheimer's disease (AD). Here we show that ErbB3 binding protein 1 (EBP1)/proliferation-associated 2G4 (PA2G4) interacts with presenilin, a catalytic subunit of γ-secretase, inhibiting Aβ production. Mice lacking forebrain Ebp1/Pa2g4 recapitulate the representative phenotypes of late-onset sporadic AD, displaying an age-dependent increase in Aβ deposition, amyloid plaques and cognitive dysfunction.

Dual-targeting CRISPR-CasRx reduces C9orf72 ALS/FTD sense and antisense repeat RNAs in vitro and in vivo.

The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic GC repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy.

Transcriptionally downregulated GABAergic genes associated with synaptic density network dysfunction in temporal lobe epilepsy.

Purpose: Temporal lobe epilepsy (TLE) is a brain network disorder closely associated with synaptic loss and has a genetic basis. However, the in vivo whole-brain synaptic changes at the network-level and the underlying gene expression patterns in patients with TLE remain unclear.

Methods: In this study, we utilized a positron emission tomography with the synaptic vesicle glycoprotein 2 A radioligand [F]SynVesT-1 cohort and two independent transcriptome datasets to investigate the topological properties of the synaptic density similarity network (SDSN) in TLE and its correlation with significantly dysregulated risk genes.

Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.

NAD+ plays a pivotal role in energy metabolism and adaptation to external stimuli and stressful conditions. A significant reduction in intracellular NAD+ levels is associated with aging and contributes to the development of chronic cardiovascular, neurodegenerative, and metabolic diseases. It is of particular importance to maintain optimal levels of NAD+ in cells with high energy consumption, particularly in the brain.

A supercritical oil extract of seeds ameliorates Huntington's disease-like symptoms and neuropathology: the potential role of anti-oxidant and anti-inflammatory effects.

Background: Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. has various pharmacologic effects such as antioxidant and anti-inflammatory activities.