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RationaleAutism spectrum disorder (ASD), the fastest growing neurodevelopmental disorder, is characterized by social deficits, repetitive/stereotypic activity, and impaired verbal and nonverbal communication and is commonly diagnosed at early stages of life. Based on the excitatory-inhibitory imbalance theory of autism, some recent animal experiments have reported amelioration in autistic-like phenotypes in adult animals following acute treatment of NMDA antagonists. However, we suggested the neonatal period as a critical period for NMDA antagonist intervention.ObjectivesThis experiment was designed to determine the role of postnatal MK-801, an NMDA receptor blocker, in the prenatal valproic acid (VPA) rat model of ASD.MethodsThe model of autism was induced by subcutaneous administration of valproic acid (600 mg/kg) to pregnant rats at gestational day 12.5. The effects of MK-801 (0.03 mg/kg, from postnatal day 6–10) in correcting ASD-associated behaviors in male offspring were assessed by open-field, three-chambered social interaction tests. Moreover, the nociceptive threshold was measured by tail flick and hot plate. Behavioral tests were performed on PND 55–60. Nissl staining was performed to confirm the safety of 0.03 mg/kg MK-801 for the brain.ResultsWe reported that MK-801 rescued social deficits, repetitive behaviors (self-grooming), anxiety-related behavior, and the low nociceptive threshold in the VPA-treated rats. Further, histological examination showed that there were no significant differences among all the groups in terms of the neuronal survival rate.ConclusionsOur results showed that postnatal low-dose MK-801 improved ASD-associated behaviors in the VPA-treated rats and that early exposure to NMDA antagonist resulted in permanent changes in adult behavior.

Exposure to prenatal stress (PS) leads to the offspring's vulnerability towards the development of cognitive and behavioral disorders. Laterodorsal tegmentum (LDT) is a part of the brainstem cholinergic system that is believed to play a pivotal role in the stress-associated progression of anxiety, memory impairment, and addictive behaviors. In this study, we aimed to investigate the electrophysiological alterations of LDT cholinergic neurons and its accompanied behavioral and cognitive outcomes in the offspring of mice exposed to physical or psychological PS. Swiss Webster mice were exposed to physical or psychological stress on the tenth day of gestation. Ex vivo investigations in LDT brain slices of adolescent male offspring were performed to evaluate the effects of two stressor types on the activity of cholinergic neurons. Open field test, elevated plus maze, passive avoidance test, and conditioned place preference were conducted to assess behavioral and cognitive alterations in the offspring. The offspring of both physical and psychological PS-exposed mice exhibited increased locomotor activity, anxiety-like behavior, memory impairment, and preference to morphine. In both early- and late-firing cholinergic neurons of the LDT, stressed groups demonstrated higher firing frequency, lower adaptation ratio, decreased action potential threshold, and therefore increased excitability compared to the control group. The findings of the present study suggest that the hyperexcitability of the cholinergic neurons of LDT might be involved in the development of PS-associated anxiety-like behaviors, drug seeking, and memory impairment.

Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, this crucial metabolic interplay during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in the 5xFAD hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle metabolism mapped by stable 13 C isotope tracing. Particularly, reduced astrocyte TCA cycle activity and decreased glutamine synthesis led to hampered neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, the cerebral cortex of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism, which may suggest a metabolic compensation in this brain region. We found limited changes when we explored the brain proteome and metabolome of the 5xFAD mice, supporting that the functional metabolic disturbances between neurons and astrocytes are early primary events in AD pathology. In addition, synaptic mitochondrial and glycolytic function was selectively impaired in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex regional and cell-specific metabolic adaptations in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunctions in AD.

In this study, a magnetic metal–organic framework (MMOF) was synthesized and post-modified with poly(propyleneimine) dendrimer to fabricate a novel functional porous nanocomposite for adsorption and recovery of palladium (Pd(II)) from aqueous solution. The morphological and structural characteristics of the prepared material were identified by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmet–Teller (BET) isotherm, and vibrating sample magnetometer (VSM). The results confirmed the successful synthesis and post-modification of MMOF. Semispherical shape particles (20–50 nm) with appropriate magnetic properties and a high specific surface area of 120 m 2 /g were obtained. An experimental design approach was performed to show the effect of adsorption conditions on Pd(II) uptake efficiency of the dendrimer-modified magnetic adsorbent. The study showed that the Pd(II) uptake on dendrimer-modified MMOF was well described by the Langmuir isotherm model with the highest uptake capacity of 291 mg/g under optimal condition (adsorbent content of 12.5 mg, Pd ion concentration of 80 ppm, pH = 4, and contact time of 40 min). The adsorption kinetics of Pd(II) ions was suggested to be a pseudo-first-order model. The results revealed a faster adsorption rate and higher adsorption capacity (about 43%) for dendrimer-modified MMOF. Finally, the reusability of the provided adsorbent was evaluated. This work provides a valuable strategy for designing and developing efficient magnetic adsorbents based on MOFs for the adsorption and recovery of precious metals.

Oxidative stress and mitochondrial dysfunction are involved in the mechanisms of cardiac toxicity induced by aluminum phosphide (AlP). AlP-induced cardiotoxicity leads to cardiomyocyte death, cardiomyopathy, cardiac dysfunction, and eventually severe heart failure and death. Importantly, protecting cardiomyocytes from death resulting from AlP is vital for improving survival. It has been reported that flavonoids such as myricetin (Myr) act as modifiers of mitochondrial function and prevent mitochondrial damage resulting from many insults and subsequent cell dysfunction. In this study, the ameliorative effect of Myr, as an important antioxidant and mitochondrial protective agent, was investigated in cardiomyocytes and mitochondria isolated from rat heart against AlP-induced toxicity, oxidative stress, and mitochondrial dysfunction. Treatment of AlP (20 μg/ml) significantly increased cytotoxicity; reduced glutathione (GSH) depletion, cellular reactive oxygen species (ROS) formation, malondialdehyde (MDA) level, ATP depletion, caspase-3 activation, mitochondrial membrane potential (ΔΨm) collapse, and lysosomal dysfunction; and decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in intact cardiomyocytes. Also, treatment of AlP (20 μg/ml) significantly increased mitochondrial dysfunction and swelling in isolated mitochondria. Myr (80 µM) appeared to ameliorate AlP-induced cytotoxicity in isolated cardiomyocytes; significantly lessened the AlP-stimulated intracellular ROS and MDA production and depletion of GSH; and increased the activities of SOD, CAT, and GSH-Px. Furthermore, Myr (40 and 80 µM) lowered AlP-induced lysosomal/mitochondrial dysfunction, ATP depletion, and caspase-3 activation. In the light of these findings, we concluded that Myr through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted an ameliorative role in AlP-induced toxicity in isolated cardiomyocytes and mitochondria, and it would be valuable to examine its in vivo effects.

Objective Essential tremor (ET) as a neurological disorder is accompanied by cognitive and motor disturbances. Despite the high incidence of ET, the drug treatment of ET remains unsatisfactory. Recently, abscisic acid (ABA) has been reported to have positive neurophysiological effects in mammals. Here, the effects of ABA on harmaline‐induced motor and cognitive impairments were investigated in rats. Methods Male Wistar rats weighing 120–140 g were divided into control, harmaline (30 mg/kg, ip), ABA vehicle (DMSO+normal saline), and ABA (10 μg/rat, icv, 30 min before harmaline injection) groups. Exploratory, balance and motor performance, anxiety, and cognitive function were assessed using footprint, open field, wire grip, rotarod, and shuttle box tests. Results The results indicated that ABA (10 μg/rat) can improve harmaline‐induced tremor in rats. The administration of ABA significantly increased time spent on wire grip and rotarod. In addition, ABA had a promising effect against the cognitive impairments induced by harmaline. Conclusion Taken together, ABA has positive effects on locomotor and cognitive impairments induced by tremor. However, further studies are required to determine the exact mechanisms of ABA on the ET. Abscisic acid affected explorative and gait disturbances induced by harmaline. Abscisic acid typically ameliorated harmaline induced tremor. Pretreatment with Abscisic acid protects against harmaline‐induced alterations.

Dysregulation of signaling pathways contributes substantially to the initiation and progression of laryngeal squamous cell carcinoma (LSCC). This study aimed to elucidate the mTOR and S6 kinase ( S6K ) gene expression levels, clinical significance, interplay of the mTOR/ S6K axis, miR-30a-3p , and the long non-coding RNA CASC15 in LSCC using bioinformatics tools. RNA-seq datasets (TCGA and GEO) were analyzed through bioinformatics and network-based tools to identify candidate pathways, miRNAs, and lncRNAs using R and Cytoscape. mTOR , S6K , miR-30a-3p , and CASC15 gene expression levels and mTOR and S6K protein values were measured in paired tumor ( n  = 54) and adjacent normal tissues ( n  = 54) using RT-qPCR and western blotting, respectively. Network analysis predicted that the mTOR/S6K regulatory axis is associated with miR-30a-3p and CASC15 . The mTOR ( p  < 0.01), S6K ( p  < 0.0001), and CASC15 ( p  = 0.021) gene expression levels were significantly upregulated, whereas miR-30a-3p was markedly downregulated ( p  < 0.0001). miR-30a-3p expression levels showed inversely correlated to mTOR ( p  = 0.05) and S6K ( p  = 0.01), while CASC15 correlated positively to both mTOR ( p  = 0.00) and S6K ( p  = 0.00). The mTOR/S6K signaling axis is markedly activated in LSCC. CASC15 may act as an oncogenic lncRNA, whereas miR-30a-3p may function as a tumor-suppressive miRNA, suggesting their potential as molecular targets in LSCC.

Multiple sclerosis (MS) is characterized by chronic neuroinflammation and progressive demyelination, with current therapies failing to adequately address both processes simultaneously. Helminth-derived excretory-secretory products (ESP) are immunomodulatory molecules that suppress host inflammation and are promising candidates for MS treatment. However, their capacity to promote remyelination remains poorly understood. This study investigated the effects of Fasciola hepatica ESP in the cuprizone-induced demyelination model. Male C57BL/6 mice were divided into four groups: control (CON), control + FES (CON + FES), cuprizone (CUP), and cuprizone + FES (CUP + FES). FES was administered intraperitoneally during the demyelination phase. Motor and cognitive functions were evaluated using open field, rotarod, wire grip, and shuttle box tests. Neuroinflammation was assessed by measuring TNF and IL-1β levels, while myelin-related changes were evaluated by MBP and Olig2 expression (ELISA and qPCR) and Luxol Fast Blue staining. FES treatment significantly reduced pro-inflammatory cytokines, increased MBP and Olig2 levels, improved myelin integrity, and enhanced motor and cognitive performance compared to untreated cuprizone mice, though full recovery to control levels was not achieved. These findings demonstrate that FES attenuates neuroinflammation and is associated with partial improvements in myelin-related outcomes in the cuprizone model, supporting the therapeutic potential of helminth-derived molecules for MS.

A novel sorbent consisting of magnetic oxidized nanocelluloses modified with graphene quantum dots was prepared and used for the separation and preconcentration of dopamine. The eluted dopamine from the sorbent was determined by a designed chemiluminescence system containing luminol, H 2 O 2 , Fe 3+ , and graphene quantum dots doped with nitrogen and phosphorus. Graphene quantum dots cause an increase in the intensity of the chemiluminescence system of luminol-H 2 O 2 , but the presence of Fe 3+ ions in this system decreases its intensity because of the sorption of the Fe 3+ ions on the surface of P, N-graphene quantum dots. However, the addition of dopamine resulted in the retrieval of P, N-graphene quantum dots, as well as the chemiluminescence intensity, due to the formation of its complex with Fe 3+ . The sorbent made of magnetic oxidized nanocelluloses modified with graphene quantum dots was characterized by various analytical techniques, and the effective parameters on the extraction of dopamine were investigated and optimized. Under the optimized conditions, the method displayed good linearity in the concentration range 0.25–17.5 µg L −1 for dopamine ( R 2  = 0.9918) with a limit of detection of 0.054 µg L −1 . The intra- and inter-day relative standard deviations at a 10.0 µg L −1 concentration level of dopamine ( n  = 6) were 2.6 and 4.1%, respectively. This method was successfully applied to the extraction and determination of dopamine in human serum and urine samples. Graphical abstract

Evaporation is a basic element in the hydrological cycle that plays a vital role in a region's water balance. In this paper, the Wild Horse Optimizer (WHO) algorithm was used to optimize long short-term memory (LSTM) and support vector regression (SVR) to estimate daily pan evaporation (Ep). Primary meteorological variables including minimum temperature (Tmin), maximum temperature (Tmax), sunshine hours (SSH), relative humidity (RH), and wind speed (WS) were collected from two synoptic meteorological stations with different climates which are situated in Fars province, Iran. One of the stations is located in Larestan city with a hot desert climate and the other is in Abadeh city with a cold dry climate. The partial mutual information (PMI) algorithm was utilized to identify the efficient input variables (EIVs) on Ep. The results of the PMI algorithm proved that the Tmax, Tmin, and RH for Larestan station and also the Tmax, Tmin, and SSH for Abadeh station are the EIVs on Ep. The results showed the LSTM–WHO hybrid model for both stations can ameliorate the daily Ep estimation and it can also reduce the estimation error. Therefore, the LSTM–WHO hybrid model was proposed as a powerful model compared to standalone models in estimating daily Ep.