Behavioral Experiments Research Articles

Intranasal delivery of hMSC-derived supernatant for treatment of ischemic stroke by inhibiting the pro-inflammatory polarization of neutrophils

BackgroundStem cells utilized for ischemic stroke treatment often display unstable homing capabilities and diminished activity in vivo, limiting their neuroprotective efficacy. Furthermore, the optimal delivery route for stem cells remains undetermined. While the cytokines secreted by stem cells show promise in modulating post-stroke inflammation, the direct application of these supernatants in ischemic stroke treatment and the underlying mechanisms are still unclear.MethodsSecretory supernatants (hMSC-L) and cell lysate products (hMSC-M) from primary human umbilical cord mesenchymal stem cells-cultured medium were administered intranasally to mice with cerebral ischemia. The neuroprotective effects of hMSC-L and hMSC-M were assessed with TTC staining, behavioral tests and pathological staining. Flow cytometry and qPCR evaluated the expression of immune cells and cytokines in the CNS and peripheral immune organs. In vitro, flow cytometry and ELISA measured the effects of hMSC-L and hMSC-M on N2 polarization and inflammatory cytokines expression in primary murine neutrophils. Western blot analysis determined the impact of hMSC-L and hMSC-M on the PPAR-γ/STAT6/SOCS1 pathway, which is crucial for N2 neutrophil polarization.ResultsTTC staining, behavioral experiments, and pathological assessments reveal intranasal delivery of hMSC-L and hMSC-M significantly reduces the infarct volume of mice with cerebral ischemia, improves neurological function scores, and promotes motor function recovery. Higher concentrations of hMSC-M contributed a more pronounced effect on neuropathological improvements in ischemic mice. Intranasal delivery of hMSC-L and hMSC-M significantly reduces neutrophil infiltration in the brain post-stroke and increases the proportion of anti-inflammatory N2-subtype neutrophils, boosting the expression levels of IL-10 and TGF-β. In vitro experiments demonstrate that hMSC-L and hMSC-M promote nuclear translocation of PPAR-γ in neutrophils stimulated with PMA, activating the downstream STAT6/SOCS1 signaling pathway to encourage N2-subtype neutrophil polarization.ConclusionsIntranasal delivery of hMSC-L and hMSC-M effectively ameliorates cerebral ischemic injury in mice, comparable to traditional administration routes like intravenous delivery. Treatment with hMSC-L and hMSC-M enhances the PPAR-γ/STAT6/SOCS1 pathway and improves the neuroinflammatory response post-stroke by increasing N2 neutrophil infiltration. These results provide a theoretical basis for a deeper understanding of the mechanisms of stem cell therapy and for exploring suitable delivery pathways of stem cell treatment.

The neural mechanisms of emotional flexibility influenced by the emotional valence shift direction and preparation effect.

Emotional flexibility refers to an individual's ability to change emotional responses in constantly changing environments to adapt to different situations. This study aims to use the Emotional Switching Task (EST) paradigm, combined with Electroencephalogram (EEG) technology and behavioral experiments, to explore the impact of emotional valence shift directions and preparation effects on the switching cost of emotional flexibility. The results found that when individuals switch from positive emotional valence to positive emotional valence, the switching cost is smaller than other transition directions. In addition, emotional flexibility exhibits a preparation effect, with a 2000 ms preparation time resulting in a smaller switching cost than a 600 ms preparation time. The electrophysiological data, more specifically the N2, CNV, SPN and LPP components, reveal the neural mechanisms by which emotional valence shift direction and preparation time influence emotional flexibility across the three neural computational stages of emotion regulation. This study is beneficial for establishing a potential mechanism model for the switching cost of emotional flexibility.

Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway.

This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression. A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting. The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA. EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.

Leveraging Metabolomics and Ionomics to Illuminate Aluminum-Induced Toxicity in Mouse Organs

Aluminum, a widely prevalent environmental pollutant, has been established to exert toxic effects on multiple organs in the human body. To gain a comprehensive understanding of these toxic effects and the mechanisms involved, this study aimed to assess potential correlations between metabolites and ion data through metabolomic and ionomic analyses. We sought to explore the intricate impact of aluminum on various organs in mice. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were employed to conduct metabolomic and ionomic analyses on the hippocampus, cortex, heart, liver, spleen, lung, kidney, bone, intestine, stomach, and serum of both control and aluminum-exposed mice. Besides, histological examinations and behavioral experiments were conducted. Multivariate analysis revealed 91 differential metabolites across various organs, primarily encompassing amino acids, fatty acids, and carbohydrates. The implicated abnormal metabolic pathways included amino acid metabolism, arachidonic acid metabolism, and glutathione metabolism. Additionally, alterations in the homeostasis of ions such as manganese, zinc, selenium, iron, copper, phosphorus, magnesium, and calcium were observed in various organs, potentially influencing the activity of critical enzymes. The changes in these potential biomarkers and ions suggest toxic mechanisms of aluminum exposure involving oxidative stress, inflammatory responses, cellular signal dysregulation, disruption of key enzyme activities, and impaired energy metabolism. This study provides a novel perspective on understanding the toxic mechanisms of aluminum exposure, potentially contributing to the prevention and treatment of aluminum toxicity.

Predictive learning as the basis of the testing effect

A prominent learning phenomenon is the testing effect, meaning that testing enhances retention more than studying. Emergent frameworks propose fundamental (Hebbian and predictive) learning principles as its basis. Predictive learning posits that learning occurs based on the contrast (error) between a prediction and the feedback on that prediction (prediction error). Here, we propose that in testing (but not studying) scenarios, participants predict potential answers, and its contrast with the subsequent feedback yields a prediction error, which facilitates testing-based learning. To investigate this, we developed an associative memory network incorporating Hebbian and/or predictive learning, together with an experimental design where human participants studied or tested English-Swahili word pairs followed by recognition. Three behavioral experiments (N = 80, 81, 62) showed robust testing effects when feedback was provided. Model fitting (of 10 different models) suggested that only models incorporating predictive learning can account for the breadth of data associated with the testing effect. Our data and model suggest that predictive learning underlies the testing effect.

Biofilm-modified Prussian blue improves memory function in late-stage Alzheimer's disease mice with triple therapy.

Alzheimer's disease (AD) is a neurodegenerative disease that is significantly characterized by cognitive and memory impairments, which worsen significantly with age. In the late stages of AD, metal ion disorders and an imbalance of reactive oxygen species (ROS) levels occur in the brain microenvironment, which causes abnormal aggregation of β-amyloid (Aβ), leading to a significant worsening of the AD symptoms. Therefore, we designed a composite nanomaterial of macrophage membranes-encapsulated Prussian blue nanoparticles (PB NPs/MM). Prussian blue nanoparticles (PB NPs) are capable of chelating Cu2+ and reducing ROS. Macrophage membranes (MM) have advantages over liposomal and erythrocyte membrane carriers, including inflammatory targeting capabilities and more effective immune evasion. Concurrently, the excellent photothermal ability of PB NPs can briefly open the blood-brain barrier (BBB) under near-infrared laser irradiation, which improves the transport efficiency of PB NPs/MM across the BBB and ablates Aβ deposition, thus achieving optimal therapeutic efficacy. In vitro experiments demonstrated that PB NPs/MM is a multifunctional nanosystem, which can effectively inhibit Cu2+-induced Aβ monomers aggregation, photothermally depolymerize Aβ fibrils, and attenuate oxidative stress through the combined treatment of chelating metals, photothermal therapy and scavenging ROS. In behavioral experiments, it also significantly improved the cognitive and learning deficits in late-stage APP/PS1 mice, thereby providing new ideas for the treatment of late-stage AD and other neurodegenerative diseases.

Neurotoxicity study of cenobamate-induced zebrafish early developmental stages.

Cenobamate (CNB) is a novel anti-seizure medication with significant efficacy in treating epilepsy. However, in clinical trials, the most common adverse reactions observed in patients are central nervous system (CNS) symptoms. In animal studies, administration of CNB during pregnancy or lactation has been associated with adverse effects on neurodevelopment in offspring. To optimize the clinical use of CNB, we investigated the neurotoxicity of different concentrations of CNB (10, 20, 40, 80, and 160μM) on zebrafish embryos. Following exposure, zebrafish embryos exhibited abnormal phenotypes such as shortened body length, impaired yolk sac absorption, and decreased heart rate. Behavioral experiments showed that CNB caused abnormal movements such as decreased spontaneous tail curling frequency, shortened total movement distance, and reduced average movement speed. We also found that CNB leads to increased acetylcholinesterase (AChE) activity levels in zebrafish embryos, along with differential expression of neurodevelopment-related genes such as nestin, gfap, synapsin IIa, and gap43. In summary, our research findings indicated that CNB may induce developmental and neurotoxic effects in zebrafish embryos by altering neurotransmitter systems and the expression of neurodevelopmental genes, thereby influencing behavior. This study will provide information for the clinical use of CNB, aiming to benefit more epilepsy patients through its appropriate administration.

D-Serine disrupts Cbln1 and GluD1 interaction and affects Cbln1-dependent synaptic effects and nocifensive responses in the central amygdala

Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission in the nervous system. In addition to NMDA receptor co-agonists, D-serine is a ligand for glutamate delta receptors (GluDs) and interacts with the ligand-binding domain with low affinity. However, D-serine binding does not lead to typical ion channel currents in GluD1 or GluD2 but may contribute to synaptic plasticity. In the developing brain, D-serine binding to GluD2 facilitates long-term depression at parallel fiber-Purkinje cell synapses. However, the influence of D-serine on GluD1's interaction with its amino terminal domain synaptogenic ligand Cbln1 and its subsequent impact on synaptic function and behavior remains unexplored. Here, we found that D-serine inhibited the interaction between Cbln1 and GluD1 in an in vitro cell-binding assay. This effect was concentration-dependent, with an IC50 value of ~ 300 µM. Furthermore, in ex vivo central amygdala (CeA) slices application of recombinant Cbln1 (rCbln1), consistent with its synaptogenic property, produced a robust increase in excitatory neurotransmission and GluD1 expression. This effect of rCbln1 was partially blocked by pre-treatment with D-serine. Finally, in behavioral experiments, we observed that the pro-nociceptive effect of intra-CeA injection of rCbln1 was inhibited by pre-treatment with D-serine. In addition, the antinociceptive effect of intra-CeA rCbln1 injection in an inflammatory pain model was blocked by D-serine. Overall, these results demonstrated that D-serine binding to GluD1 reduces its interaction with Cbln1, which may be relevant to synaptic plasticity and behavior.Graphical

Smooth or sticky? An analysis of service variability

This study examines the impact of service variability on customer-perceived service quality across various stages of the customer experience journey. Through a behavioral experiment, the findings reveal that the overall perceived service quality is influenced by the interplay between the mean and variability of service quality. Positive variability can elevate service quality at specific phases, yet its impact is contingent on the average service level. Moreover, the order in which positive and negative variability occur contributes to shaping overall perception. The research also indicates that new guests are more susceptible to variability than repeat customers. This study enriches the debate between consistency and unpredictability in service offerings, providing valuable insights to refine tourism service design and enhance overall customer satisfaction.

Effects of treadmill running on anxiety- and craniofacial pain-like behaviors with histone H3 acetylation in the brain of mice subjected to social defeat stress.

This study examined the effects of treadmill running (TR) regimens on craniofacial pain- and anxiety-like behaviors, as well as their effects on neural changes in specific brain regions of male mice subjected to repeated social defeat stress (SDS) for 10 days. Behavioral and immunohistochemical experiments were conducted to evaluate the impact of TR regimens on SDS-related those behaviors, as well as epigenetic and neural activity markers in the anterior cingulate cortex (ACC), insular cortex (IC), rostral ventromedial medulla (RVM), and cervical spinal dorsal horn (C2). Behavioral responses were quantified using multiple tests, while immunohistochemistry measured histone H3 acetylation, histone deacetylases (HDAC1, HDAC2), and neural activity markers (FosB and phosphorylated cAMP response element-binding protein (pCREB). The effects of both short-term TR (2 days, TR2) and long-term TR (10 days, TR10) regimens were conducted. TR10 significantly reduced anxiety- and formalin-evoked craniofacial pain-like behaviors in SDS mice. It normalized SDS-induced increases in histone H3 acetylation in both the anterior and posterior portions of the ACC, as well as the anterior portion of the IC. These inhibitory effects were also observed in SDS-related increases in HDAC1, FosB, and pCREB expression. Additionally, TR10 normalized increased histone H3 acetylation in the RVM and C2 regions, with specific effects on FosB and pCREB expression observed in the C2 region. In contrast, TR2 showed limited effects on craniofacial pain-like behaviors but reduced anxiety-like behaviors in SDS mice. Under sham conditions, TR2 had minimal impact on histone H3 acetylation. Paradoxically, TR2 increased formalin-evoked craniofacial pain-like behaviors during the early phase despite not altering acetylated histone H3 expression. In conclusion, the TR10 regimen is effective in attenuating SDS-induced craniofacial pain- and anxiety-like behaviors, likely by normalizing epigenetic modifications and neural activity in key brain regions.

Electrophysiological signatures of the effect of context on exploration: Greater attentional and learning signals when exploration is costly.

Humans are excellent at modifying our behaviour depending on context. For example, humans will change how they explore when losses are possible compared to when they are not possible. However, it remains unclear what specific cognitive and neural processes are modulated when exploring in different contexts. Here, we had participants learn within two different contexts: in one the participants could lose points while in the other the participants could not. Our goal was to determine how the inclusion of losses impacted human exploratory behaviour (experiment one), and whether we could explain the neural basis of these effects using EEG (experiment two). In experiment one, we found that participants preferred less-variable choices and explored less often when losses were possible. In addition, computational modelling revealed that participants engaged in less random exploration, had a lower rate of learning, and showed less choice perseverance when losses were possible. In experiment two, we replicated these effects while examining a series of neural signals involved in exploration. During exploration, signals tied to working memory and learning (P3b), attention orienting (P3a) and motivation (late positive potential; an exploratory analysis) were also enhanced when losses were possible. These neural differences contribute to why exploratory behaviour is changed by different learning contexts and can be explained by the theoretical claim that losses recruit attention and lead to increased task focus. These results provide insight into the cognitive processes that underlie exploration, and how exploratory behaviour changes across contexts.

Harmonizing the past: EEG-based brain network unveil modality-specific mechanisms of nostalgia

IntroductionNostalgia is a complex emotional experience involving fond memories of the past and mild sadness, characterized by positive emotions associated with reflecting on previous events. It can awaken emotional memories of loved ones or significant events, contributing to an increase in positive emotions. An unresolved question regarding nostalgia is whether different channels of nostalgia input exhibit distinct mechanisms.MethodsThis study examined the emotional and neural effects of nostalgia using various sensory channels through behavioral experiments and electroencephalography (EEG) measurements conducted with college students in China. Participants' emotions were elicited using nostalgic and non-nostalgic stimuli presented through three different sensory channels: auditory (sound only), visual (e.g., still images or synchronized lyrics related to music), and audiovisual (a combination of sound and visual elements, such as music videos).ResultsThe results demonstrated that nostalgic stimuli elicited significantly higher levels of emotional arousal, pleasure, nostalgia, and dominance compared to non-nostalgic stimuli. At the neural level, nostalgic stimuli enhanced the connection strength, global and local efficiency, and diminished eigenpath length of brain networks in the alpha and gamma bands. Additionally, nostalgia through the auditory channel induced higher activity intensity in the theta and gamma bands and increased brainwave amplitudes in the alpha bands. The audiovisual channel was capable of triggering stronger alpha-wave responses than the visual channel alone.DiscussionThese findings suggest that nostalgia effectively triggers positive emotional states and enhances cognitive processing. The audiovisual channel, in particular, showed advantages in eliciting alpha-wave responses. Further research is needed to explore the potential of nostalgia as an adjunctive therapeutic tool.

Hair Follicle Mesenchymal Stem Cells Induce Neural Regeneration and Repair after Transient Ischemic Stroke.

To investigate the effect of hair follicle mesenchymal stem cells (HFMSCs) in ischemic stroke. Materials & methods: Rat transient ischemic stroke model was established to verify the effect of HFMSC transplantation. Behavioral experiment and TTC staining were used to estimate neurological outcome after HFMSC therapy. Pathological experiments were used to investigate the therapeutic roles of HFMSCs. HFMSCs inhibited neural apoptosis and promoted neural proliferation. The number of neural cells around ischemic core increased after HFMSC transplantation. Besides, the grafted HFMSCs expressed neuron-specific marker in the penumbra. Finally, HFMSCs diminished infarct area and improved neurological scores. HFMSCs can improve neurological outcome via anti-apoptosis and promoting neural stem cells proliferation, indicating their therapeutic potential in ischemic stroke.

Metformin attenuated depressive-like behaviors by suppressing TRPV1/NLRP3 mediated neuroinflammation in the hypothalamus of allergic rhinitis mice.

In addition to nasal symptoms, allergic rhinitis (AR) has increasingly been reported to be associated with depression-like behaviors. Recent evidence suggests that neuroinflammation in the hypothalamus may cause these depressive symptoms in AR. However, the precise mechanisms and effective treatments remain to be elucidated. This study investigated the ameliorative effects of metformin on neuroinflammation in the hypothalamus, depressive-like behavior and the underlying molecular mechanisms of AR mice. Mice were administered ovalbumin (OVA) intranasally to induce allergic rhinitis and subsequently subjected to behavioral experiments to detect depressive-like behavior. The roles of the TRPV1/NLRP3 pathway in depression-like behaviors in AR were examined in vivo. Additionally, the mechanism of TRPV1/NLRP3-mediated neuroinflammation was investigated in vitro. Finally, metformin was utilized to explore its possible mechanisms and efficacy in treating depressive-like behavior in AR. AR mice exhibited significant depressive-like behavior, which was attenuated by metformin. The number of Iba-1+ microglia significantly increased in the hypothalamus of AR mice. The expression of NLRP3 was significantly upregulated in the hypothalamus, activating microglia. Metformin ameliorated the neuropsychiatric symptoms by reducing NLRP3 expression in the hypothalamus. Moreover, metformin inhibited LPS-induced upregulation of the TRPV1/NLRP3 signaling pathway in microglial cell line, an effect that can be reversed by the TRPV1-specific agonist capsaicin. Increased TRPV1 expression activates the NLRP3 inflammasome in hypothalamic microglia, promoting the pathological process of depressive-like behavior in AR mice. Metformin could effectively treat neuroinflammation by regulating microglia via TRPV1 downregulation, indicating its potential as a treatment for depressive-like behaviors in AR.

Butylphthalide may inhibit blood-brain barrier disruption through complement-related pathways to alleviate cognitive impairment in epileptic mice.

Temporal lobe epilepsy is often accompanied by comorbid symptoms such as anxiety, depression, and cognitive dysfunction. Research indicates a close relationship between blood-brain barrier (BBB) impairment and these symptoms. DL-3n-butylphthalide (NBP) has been reported to protect the BBB, but the molecular mechanisms by which NBP protects the BBB in epilepsy models remain unclear. This study investigated the protective effects of NBP on the BBB in epileptic mice to alleviate the comorbid symptoms associated with epilepsy. We utilized Mendelian randomization to explore the association between VEGFA and epilepsy. In the animal experiments, adult male C57BL/6 mice were used to establish a KA-induced epilepsy model, receiving daily intraperitoneal injections of NBP for 30days. After this period, behavioral experiments and Western blot analyses were conducted to assess whether the comorbid symptoms of epilepsy and BBB disruption were alleviated. Subsequently, RNA sequencing was performed to analyze potential signaling pathways involved in the pharmacological effects of NBP. Elevated circulating levels of VEGFA may be a risk factor for the onset of epilepsy. Animal experiments demonstrated that NBP treatment improved BBB disruption in KA-induced epileptic mice and alleviated depressive and anxious behaviors, as well as cognitive impairments. RNA sequencing results suggest that the pharmacological effects of NBP may be mediated through the inhibition of complement and coagulation cascades. NBP can protect the integrity of the BBB in KA-induced epileptic mice, inhibiting depression, anxiety behaviors, and cognitive dysfunction. This pharmacological effect may be associated with pathways involving complement and coagulation cascades.

The benefit of extrinsic motivation on effortful cognitive control is influenced by need for cognition.

Extrinsic motivation can foster effortful cognitive control. Moreover, the selective coupling of extrinsic motivation on low- versus high-control demands tasks would exert an additional impact. However, to what extent their influences are further modulated by the level of Need for Cognition (NFC) remains unclear. Thus, the current study sought to address this question. To this end, we conducted two behavioral experiments wherein cognitive control was triggered by the confound-minimized Stroop task and the NFC questionnaire was administered. Two different forms of extrinsic motivation were manipulated at the block level. In Experiment 1, extrinsic motivation was triggered by evaluative feedback. In Experiment 2, extrinsic motivation was triggered by reward incentives, while evaluative feedback was selectively coupled with low (congruent)- or high (incongruent)- control demands trials. The results indicated that two forms of extrinsic motivation (evaluative feedback vs. reward incentives) presented distinctive effects on effortful cognitive control; while their benefits on overall performance were further influenced by NFC. Interestingly, when incongruent rather than congruent trials were selectively coupled with reward incentives, not only conflict processing, but also overall performance for low-NFC participants only, benefited from this scenario. Taken together, the current study shows that extrinsic motivation can boost cognitive control, which gain was further reduced by high NFC.

Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation.

Epidemiological investigations have revealed a significant association between alcohol consumption and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Nevertheless, the potential mechanisms are still inadequately revealed. This research aimed to investigate the impact of alcohol on CP/CPPS using an animal model and to elucidate the underlying mechanisms. We first established the widely used animal model for CP/CPPS, experimental autoimmune prostatitis (EAP). During the induction of EAP, mice were fed with alcohol or control diet. The HE staining, ELISA, and behavioral experiments were employed to assess the severity of inflammation in EAP mice and EAP-alcohol mice. Patients with a history of chronic alcohol consumption were also included to evaluate the effects of chronic alcohol consumption on CP/CPPS. Subsequently, proteomic analysis, flow cytometry, immunofluorescence, Western blotting, and immunohistochemistry were utilized to investigate the underlying mechanism involved both in vivo and in vitro. HE staining, ELISA, and behavioral experiments showed that alcohol exacerbated the severity of EAP in mice and patients. Proteomic and KEGG pathway analyses showed that abnormal Th1 differentiation and PI3K/AKT/mTOR pathway were significantly enriched. Subsequent mechanistic research showed that alcohol significantly activated PI3K/AKT/mTOR pathway and increased the Th1 cell differentiation both in vivo and in vitro. In contrast, PI3K inhibitor LY294002 and shRNA-PI3K plasmid inhibited PI3K/AKT/mTOR pathway activation, reduced Th1 cell differentiation, and alleviated EAP inflammation severity, respectively. Our study is the first to demonstrate that alcohol intake promotes Th1 cell differentiation and exacerbates EAP by activating the PI3K/AKT/mTOR pathway. Additionally, the role of LY294002 in inhibiting PI3K/AKT/mTOR pathway to relieve EAP suggests that it can serve as a promising therapeutic target for CP/CPPS.

Targeting audiences' moral values shapes misinformation sharing.

Does aligning misinformation content with individuals' core moral values facilitate its spread? We investigate this question in three behavioral experiments (N1a = 615; N1b = 505; N₂ = 533) that examine how the alignment of audience values and misinformation framing affects sharing behavior, in conjunction with analyzing real-world Twitter data (N = 20,235; 809,414 tweets) that explores how aligning the moral values of message senders with misinformation content influences its dissemination in the context of COVID-19 vaccination misinformation. First, we investigate how aligning messages' moral framing with participants' moral values impacts participants' intentions to share true and false news headlines and whether this effect is driven by a lack of analytical thinking. Our results show that framing a post such that it aligns with audiences' moral values leads to increased sharing intentions, independent of headline familiarity, and participants' political ideology but find no effect of analytical thinking. Furthermore, we find that moral alignment facilitates sharing misinformation more so than true information. Next, we use natural language processing to determine messages' moral framing and senders' political ideology. We find that an alignment of moral framing and ideology facilitates the spread of misinformation. Our findings suggest that (a) targeting audiences' core values can be used to influence the dissemination of (mis)information on social media platforms; (b) partisan divides in misinformation sharing can be, at least partially, explained through alignment between audiences' underlying moral values and moral framing that often accompanies content shared online; and (c) this effect is driven by motivational factors. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington’s disease models

BackgroundHD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention.MethodsThe CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA. This therapeutic effect was substantiated in various models: HEK 293 T cell, the HD 140Q-KI mouse, and the HD-KI pig model. The efficiency of the knockdown was analyzed through Western blot and RT-qPCR. Additionally, neuropathological changes were examined using Western blot, immunostaining, and RNA sequencing. The impact on motor abilities was assessed via behavioral experiments, providing a comprehensive evaluation of the treatment's effectiveness.ResultsCRISPR/CasRx system can significantly reduce HTT mRNA levels across various models, including HEK 293 T cells, HD 140Q-KI mice at various disease stages, and HD-KI pigs, and resulted in decreased expression of mHTT. Utilizing the CRISPR/CasRx system to knock down HTT RNA has shown to ameliorate gliosis in HD 140Q-KI mice and delay neurodegeneration in HD pigs.ConclusionsThese findings highlight the effectiveness of the RNA-targeting CRISPR/CasRx as a potential therapeutic strategy for HD. Furthermore, the success of this approach provides valuable insights and novel avenues for the treatment of other genetic disorders caused by gene mutations.

Experiment and Numerical Simulation Study of Mechanical Behavior and Failure Mechanism of a Low-Clay Siliceous Shale After Water Saturation

Experiment and Numerical Simulation Study of Mechanical Behavior and Failure Mechanism of a Low-Clay Siliceous Shale After Water Saturation