Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review).

Metformin has been the go­to medical treatment for addressing type 2 diabetes mellitus (T2DM) as a frontline oral antidiabetic. Obesity, cancer and bone deterioration are linked to T2DM, which is considered a metabolic illness. Numerous diseases associated with T2DM, such as tumours, cardiovascular disease and bone deterioration, may be treated with metformin. Intervertebral disc degeneration (IVDD) is distinguished by degeneration of the spinal disc, accompanied by the gradual depletion of proteoglycans and water in the nucleus pulposus (NP) of the IVD, resulting in lower back pain. The therapeutic effect of metformin on IVDD has also attracted much attention. By stimulating AMP­activated kinase, metformin could enhance autophagy and suppress cell senescence, apoptosis and inflammation, thus effectively delaying IVDD. The present review aimed to systematically explain the development of IVDD and mechanism of metformin in the treatment and prevention of IVDD to provide a reference for the clinical application of metformin as adjuvant therapy in the treatment of IVDD.

Ultrasensitive Wearable Pressure Sensors with Stress-Concentrated Tip-Array Design for Long-Term Bimodal Identification.

The great challenges for existing wearable pressure sensors are the degradation of sensing performance and weak interfacial adhesion owing to the low mechanical transfer efficiency and interfacial differences at the skin-sensor interface. Here, an ultrasensitive wearable pressure sensor is reported by introducing a stress-concentrated tip-array design and self-adhesive interface for improving the detection limit. A bipyramidal microstructure with various Young's moduli is designed to improve mechanical transfer efficiency from 72.6% to 98.4%. By increasing the difference in modulus, it also mechanically amplifies the sensitivity to 8.5 V kPa-1 with a detection limit of 0.14 Pa. The self-adhesive hydrogel is developed to strengthen the sensor-skin interface, which allows stable signals for long-term and real-time monitoring. It enables generating high signal-to-noise ratios and multifeatures when wirelessly monitoring weak pulse signals and eye muscle movements. Finally, combined with a deep learning bimodal fused network, the accuracy of fatigued driving identification is significantly increased to 95.6%.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Recent research progress on tumour-specific responsive hydrogels.

Most existing hydrogels, even recently developed injectable hydrogels that undergo a reversible sol-gel phase transition in response to external stimuli, are designed to gel immediately before or after implantation/injection to prevent the free diffusion of materials and drugs; however, the property of immediate gelation leads to a very weak tumour-targeting ability, limiting their application in anticancer therapy. Therefore, the development of tumour-specific responsive hydrogels for anticancer therapy is imperative because tumour-specific responses improve their tumour-targeting efficacy, increase therapeutic effects, and decrease toxicity and side effects. In this review, we introduce the following three types of tumour-responsive hydrogels: (1) hydrogels that gel specifically at the tumour site; (2) hydrogels that decompose specifically at the tumour site; and (3) hydrogels that react specifically with tumours. For each type, their compositions, the mechanisms of tumour-specific responsiveness and their applications in anticancer treatment are comprehensively discussed.

3D-QSAR, Scaffold Hopping, Virtual Screening, and Molecular Dynamics Simulations of Pyridin-2-one as mIDH1 Inhibitors.

Isocitrate dehydrogenase 1 (IDH1) is a necessary enzyme for cellular respiration in the tricarboxylic acid cycle. Mutant isocitrate dehydrogenase 1 (mIDH1) has been detected overexpressed in a variety of cancers. mIDH1 inhibitor ivosidenib (AG-120) was only approved by the Food and Drug Administration (FDA) for marketing, nevertheless, a range of resistance has been frequently reported. In this study, several mIDH1 inhibitors with the common backbone pyridin-2-one were explored using the three-dimensional structure-activity relationship (3D-QSAR), scaffold hopping, absorption, distribution, metabolism, excretion (ADME) prediction, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, R2 = 0.980, Q2 = 0.765) and comparative molecular similarity index analysis (CoMSIA, R2 = 0.997, Q2 = 0.770) were used to build 3D-QSAR models, which yielded notably decent predictive ability. A series of novel structures was designed through scaffold hopping. The predicted pIC50 values of C3, C6, and C9 were higher in the model of 3D-QSAR. Additionally, MD simulations culminated in the identification of potent mIDH1 inhibitors, exhibiting strong binding interactions, while the analyzed parameters were free energy landscape (FEL), radius of gyration (Rg), solvent accessible surface area (SASA), and polar surface area (PSA). Binding free energy demonstrated that C2 exhibited the highest binding free energy with IDH1, which was -93.25 ± 5.20 kcal/mol. This research offers theoretical guidance for the rational design of novel mIDH1 inhibitors.

SLGA-YOLO: A Lightweight Castings Surface Defect Detection Method Based on Fusion-Enhanced Attention Mechanism and Self-Architecture.

Castings' surface-defect detection is a crucial machine vision-based automation technology. This paper proposes a fusion-enhanced attention mechanism and efficient self-architecture lightweight YOLO (SLGA-YOLO) to overcome the existing target detection algorithms' poor computational efficiency and low defect-detection accuracy. We used the SlimNeck module to improve the neck module and reduce redundant information interference. The integration of simplified attention module (SimAM) and Large Separable Kernel Attention (LSKA) fusion strengthens the attention mechanism, improving the detection performance, while significantly reducing computational complexity and memory usage. To enhance the generalization ability of the model's feature extraction, we replaced part of the basic convolutional blocks with the self-designed GhostConvML (GCML) module, based on the addition of p2 detection. We also constructed the Alpha-EIoU loss function to accelerate model convergence. The experimental results demonstrate that the enhanced algorithm increases the average detection accuracy (mAP@0.5) by 3% and the average detection accuracy (mAP@0.5:0.95) by 1.6% in the castings' surface defects dataset.

Enantioselective Reductive Cyclization of Alkynyl-Tethered Cyclohexadienones Catalyzed by Rhodium Complexes.

Although various types of asymmetric cyclization reactions of 1,6-enynes have been established, simple asymmetric reductive cyclization remains underdeveloped. In this study, the enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones (1,6-enynes) has been developed via a chiral pincer rhodium catalyst, affording cis-hydrobenzofurans and cis-hydroindoles with high enantioselectivities (90-99% ee). Furthermore, several synthetic applications and preliminary inhibitory activity studies against SARS-CoV-2 3CLpro are presented.

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms.

HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics.

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher F 1 scores (average F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.

Modeling the Impact of Proactive Community Case Management on Reducing Confirmed Malaria Cases in Sub-Saharan African Countries.

Malaria continues to be a major source of morbidity and mortality in sub-Saharan Africa. Timely, accurate, and effective case management is critical to malaria control. Proactive community case management (ProCCM) is a new strategy in which a community health worker "sweeps" a village, visiting households at defined intervals to proactively provide diagnostic testing and treatment if indicated. Pilot experiments have shown the potential of ProCCM for controlling malaria transmission; identifying the best strategy for administering ProCCM in terms of interval timings and number of sweeps could lead to further reductions in malaria infections. We developed an agent-based simulation to model malaria transmission and the impact of various ProCCM strategies. The model was validated using symptomatic prevalence data from a ProCCM pilot study in Senegal. Various ProCCM strategies were tested to evaluate the potential for reducing parasitologically confirmed symptomatic malaria cases in the Senegal setting. We found that weekly ProCCM sweeps during a 21-week transmission season could reduce cases by 36.3% per year compared with no sweeps. Alternatively, two initial fortnightly sweeps, seven weekly sweeps, and finally four fortnightly sweeps (13 sweeps total) could reduce confirmed malaria cases by 30.5% per year while reducing the number of diagnostic tests and corresponding costs by about 33%. Under a highly seasonal transmission setting, starting the sweeps early with longer duration and higher frequency would increase the impact of ProCCM, though with diminishing returns. The model is flexible and allows decision-makers to evaluate implementation strategies incorporating sweep frequency, time of year, and available budget.

KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

An Empirical Investigation of the Relationships Among Self-Esteem, Depression and Self-Serving Bias in People with Internet Gaming Disorder.

Introduction: People are generally characterized by a self-serving bias which describes the tendency to ascribe positive outcomes or success to internal or personal causes (self-enhancement motivation) and ascribe negative outcomes or failure to external or situational causes (self-protection motivation). It has been found that the individuals with internet gaming disorder (IGD) who have low self-esteem and high depression exhibit an attenuated self-serving bias. However, the relationships among self-esteem, depression and self-serving bias are not clearly identified. Methods: A sample of 138 IGD participants completed self-esteem and depression scales and a causal attribution task (Study 1) to examine the relationships among self-esteem, depression and self-serving bias (both self-enhancement and self-protection). In follow-up Study 2, 28 IGD participants were recruited to undertake self-affirmation intervention which can affirm one's sense of global self-view and bolster self-esteem to explore whether self-affirmation would trigger a reduction of depression and a raise of self-serving bias. Results: The results of path analysis in Study 1 showed that the self-serving bias was predicted by self-esteem and depression, and the depression played a mediating role between self-esteem and self-serving bias. The results of Study 2 showed that the IGD participants reported higher self-esteem, lower depression and engaged in more self-protection motivation after affirming-self manipulation as compared with affirming-other manipulation. Conclusion: These findings suggest that self-esteem predicts self-serving bias through depression and self-affirmation could trigger an increase of self-esteem, further decrease depression and improve self-serving bias for the individuals with IGD. The present article clearly identified the relationships among these factors and provided a new approach to promote positive self-concept in individuals with IGD. Future research is warranted to explore the lasting benefits of self-affirmation on domains of education, relationships and gaming withdrawal for the individuals with IGD among different populations.

Understanding nanoparticle-liver interactions in nanomedicine.

INTRODUCTION: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation. AREAS COVERED: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions. EXPERT OPINION: While liver accumulation can hinder nanomedicine safety and effectiveness, it also presents opportunities for treating certain liver diseases. A thorough understanding of nanoparticle-liver interactions is essential for advancing the clinical application of nanomedicines.

Lightweight, Elastic, and Superhydrophobic Multifunctional Organic-Inorganic Fibrous Aerogels for Efficient Oily Wastewater Purification and Electromagnetic Microwave Absorption.

Lightweight and robust aerogels with multifunctionality are highly desirable to meet the technological demands of current society. Herein, we designed lightweight, elastic, and superhydrophobic multifunctional organic-inorganic fibrous hybrid aerogels which were assembled with organic aramid nanofibers and inorganic hierarchical porous carbon fibers. Thanks to the organic-inorganic fiber hybridization strategy, the optimal aerogels possessed remarkable compressibility and elasticity. Benefiting from the microscopic hierarchical porous structure of carbon fibers and the macroscopic macroporous lamellar structure of aerogels, the optimal aerogels exhibited superb lightweight property, conspicuous electromagnetic microwave absorption ability, and outstanding oily wastewater purification capacity. As for electromagnetic microwave absorption, it achieved a strong reflection loss of -41.8 dB, and the effective absorption bandwidth reached 6.86 GHz. Besides, the oil adsorption capacity for trichloromethane reached as high as 93.167 g g-1 with a capacity retention of 95.6% after 5 cycles. Meanwhile, it could act as a gravity-driven separation membrane to continuously separate trichloromethane from a trichloromethane-water mixture with a high flux of 7867.37 L·m-2·h-1, even for surfactant-stabilized water-in-n-heptane emulsions of 3794.94 L·m-2·h-1. Such a strategy might shed some light on the construction of multifunctional aerogels toward broader applications.

ZnO NPs induce miR-342-5p mediated ferroptosis of spermatocytes through the NF-κB pathway in mice.

BACKGROUND: Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated. RESULTS: We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1. CONCLUSIONS: The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.

Transcranial direct current stimulation of the prefrontal and visual cortices diversely affects early and late perceptual learning.

BACKGROUND: Research has shown that visual perceptual learning (VPL) is related to modifying neural activity in higher level decision-making regions. However, the causal roles of the prefrontal and visual cortexes in VPL are still unclear. Here, we investigated how anodal transcranial direct current stimulation (tDCS) of the prefrontal and visual cortices modulates VPL in the early and later phases and the role of multiple brain regions. METHODS: Perceptual learning on the coherent motion direction identification task included early and later stages. After early training, participants needed to continuously train to reach a plateau; once the plateau was reached, participants entered a later stage. Sixty participants were randomly divided into five groups. Regardless of the training at the early and later stages, four groups received multitarget tDCS over the right dorsolateral prefrontal cortex (rDLPFC) and right middle temporal area (rMT), single-target tDCS over the rDLPFC, and single-target tDCS over the rMT or sham stimulation, and one group was stimulated at the ipsilateral brain region (i.e., left MT). RESULTS: Compared with sham stimulation, multitarget and two single-target tDCS over the rDLPFC or rMT improved posttest performance and accelerated learning during the early period. However, multitarget tDCS and two single-target tDCS led to equivalent benefits for VPL. Additionally, these beneficial effects were absent when anodal tDCS was applied to the ipsilateral brain region. For the later period, the above facilitating effects on VPL induced by multitarget or single-target tDCS disappeared. CONCLUSIONS: This study suggested the causal role of the prefrontal and visual cortices in visual motion perceptual learning by anodal tDCS but failed to find greater beneficial effects by simultaneously stimulating the prefrontal and visual cortices. Future research should investigate the functional associations between multiple brain regions to further promote VPL.

Anthocyanins and proanthocyanidins synergistically inhibit the growth of gastric cancer cells in vitro: exploring the potential physiological activity of grape and red wine.

Red wine is rich in anthocyanins and procyanidins which possess multiple health-promoting properties. However, the synergistically anticancer effects of them on gastric cancer cells still undefined. The results showed that combination of malvidin-3-O-(6-O-coumaroyl)-glucoside-5-O-glucoside (M35GC) and procyanidin C1 could effectively inhibited the viability of MKN-28 cells with the lowest IC50 value. Mechanistically, M35GC and procyanidin C1 significantly induced cell apoptosis by reducing the ratio of Bcl-2/Bax, blocked cell cycle in G0/G1 phase by decreasing CDK4 protein and decreased glucose consumption and lactate production during aerobic glycolysis through suppressing the expression of HK2 protein in MKN-28 cells. In conclusion, induction of cell apoptosis and cell cycle arrest, as well as the inhibition of HK2 protein that participates in the glycolytic pathway and the suppression of aerobic glycolysis by M35GC and procyanidin C1 contributed to the anti-cancer effects in gastric cancer.

Calcium and vitamin D supplements and burnout of anesthesiologists: National cross-sectional study from China.

OBJECTIVE: Job burnout among anesthesiologists has been consistently high. This study evaluated the association of calcium and vitamin D supplementation with burnout among Chinese anesthesiologists. METHOD: A cross-sectional online survey was conducted during April and May 2023. Burnout was evaluated using the Maslach Burnout Inventory, which assesses emotional exhaustion, depersonalization, and low personal accomplishment. Data on calcium and vitamin D supplementations were self-reported. Sociodemographic information and medical history were also assessed. Binary and ordinal logistic regression were used to evaluate the risk of burnout and burnout levels, respectively. The relative excess risk due to interaction and the attributable proportion due to interaction were examined to determine the synergistic effects of calcium and vitamin D supplementations on burnout risk. RESULTS: Among the 4222 invited anesthesiologists, 3766 submitted eligible questionnaires. Approximately 49.8% met the criteria for general burnout. Among anesthesiologists with burnout, 58.4% experienced emotional exhaustion, 35.8% depersonalization, and 61.2% low personal accomplishment. Anesthesiologists receiving calcium supplementation had a decreased risk of emotional exhaustion (OR = .83, 95% CI = .70-.99). Supplementation of vitamin D with or without calcium was not associated with overall burnout and any of its dimensions. No additive interaction of calcium and vitamin D on burnout was observed. CONCLUSIONS: Job burnout among anesthesiologists is of concern in China. Burnout is negatively associated with calcium supplementation but not with vitamin D. Further research is warranted to confirm the mechanism and causal relationship.

Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative studies: A systematic review and meta-analysis.

Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. We aimed to determine the impact of pre-existing immunity on the vaccine effectiveness (VE) estimates. We systematically reviewed and meta-analysed 66 test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between VE estimates against infection and severe disease, and the cumulative incidence of cases before the start of the study or incidence rates during the study period. We found clear empirical evidence that higher levels of pre-existing immunity were associated with lower VE estimates. Prior infections should be treated as both a confounder and effect modificatory when the policies target the whole population or stratified by infection history, respectively.

A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels.

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.