Mechanism of agonist-induced activation of the human itch receptor MRGPRX1.

Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) are 4 primate-specific receptors that are recently reported to be responsible for many biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first identified human MRGPR, and its expression is restricted to primary sensory neurons. Due to its dual roles in itch and pain signaling pathways, MRGPRX1 has been regarded as a promising target for itch remission and pain inhibition. Here, we reported a cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 in an active conformation at an overall resolution of 3.0 Å via a NanoBiT tethering strategy. Compound 16 is a new pain-relieving compound with high potency and selectivity to MRGPRX1 over other MRGPRXs and opioid receptor. MRGPRX1 was revealed to share common structural features of the Gq-mediated receptor activation mechanism of MRGPRX family members, but the variable residues in orthosteric pocket of MRGPRX1 exhibit the unique agonist recognition pattern, potentially facilitating to design MRGPRX1-specific modulators. Together with receptor activation and itch behavior evaluation assays, our study provides a structural snapshot to modify therapeutic molecules for itch relieving and analgesia targeting MRGPRX1.

RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases.

Fork reversal is a conserved mechanism to prevent stalled replication forks from collapsing. Formation and protection of reversed forks are two crucial steps in ensuring fork integrity and stability. Five RAD51 paralogs, namely, RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, which share sequence and structural similarity to the recombinase RAD51, play poorly defined mechanistic roles in these processes. Here, using purified BCDX2 (RAD51BCD-XRCC2) and CX3 (RAD51C-XRCC3) complexes and in vitro reconstituted biochemical systems, we mechanistically dissect their functions in forming and protecting reversed forks. We show that both RAD51 paralog complexes lack fork reversal activities. Whereas CX3 exhibits modest fork protection activity, BCDX2 significantly synergizes with RAD51 to protect DNA against attack by the nucleases MRE11 and EXO1. DNA protection is contingent upon the ability of RAD51 to form a functional nucleoprotein filament on DNA. Collectively, our results provide evidence for a hitherto unknown function of RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks.

Relationship between self-esteem and quality of life in middle-aged and older patients with chronic diseases: mediating effects of death anxiety.

BACKGROUND: Many studies have explored the relationship between self-esteem and quality of life. However, few studies have elucidated the mechanisms underlying the relationship between self-esteem and quality of life in middle-aged and older patients with chronic diseases. The present study aimed to explore the mediating role of death anxiety in this relationship. METHODS: Middle-old-aged patients with chronic diseases were selected as the respondents by using a multi-stage sampling method, random number table method from October 2021 to February 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine. The Cumulative Disease Rating Scale, the Self-Esteem Scale (SES), the Chinese version of the Death Anxiety Scale (CT-DAS), and the Simplified version of the Quality of Life Scale (SF-12) were used as the researching tools to conduct the survey. SPSS26.0 was used to analysis data. AMOS 23.0 software was used to construct structural equation modeling. RESULTS: 294 valid questionnaires were collected. There were significant differences in quality of life among middle-aged and elderly patients with chronic diseases who have different physical activities, socialization, and chronic pain (P < 0.01); Self-esteem was positively associated with quality of life (r = 0.330, P < 0.01), self-esteem was negatively associated with death anxiety (r = -0.222, P < 0.01), and death anxiety was negatively associated with quality of life (r = -0.263, P < 0.01); Death anxiety partially mediated the relationship between self-esteem and quality of life, with the mediating effect accounting for 18.40% of the total effect. CONCLUSION: Death anxiety partially mediates the relationship between self-esteem and quality of life. Interventions to improve self-esteem and reduce death anxiety should be used to improve the quality of life of middle-aged and senior patients with chronic diseases.

The HSP40 family chaperone isoform DNAJB6b prevents neuronal cells from tau aggregation.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder with clinical presentations of progressive cognitive and memory deterioration. The pathologic hallmarks of AD include tau neurofibrillary tangles and amyloid plaque depositions in the hippocampus and associated neocortex. The neuronal aggregated tau observed in AD cells suggests that the protein folding problem is a major cause of AD. J-domain-containing proteins (JDPs) are the largest family of cochaperones, which play a vital role in specifying and directing HSP70 chaperone functions. JDPs bind substrates and deliver them to HSP70. The association of JDP and HSP70 opens the substrate-binding domain of HSP70 to help the loading of the clients. However, in the initial HSP70 cycle, which JDP delivers tau to the HSP70 system in neuronal cells remains unclear. RESULTS: We screened the requirement of a diverse panel of JDPs for preventing tau aggregation in the human neuroblastoma cell line SH-SY5Y by a filter retardation method. Interestingly, knockdown of DNAJB6, one of the JDPs, displayed tau aggregation and overexpression of DNAJB6b, one of the isoforms generated from the DNAJB6 gene by alternative splicing, reduced tau aggregation. Further, the tau bimolecular fluorescence complementation assay confirmed the DNAJB6b-dependent tau clearance. The co-immunoprecipitation and the proximity ligation assay demonstrated the protein-protein interaction between tau and the chaperone-cochaperone complex. The J-domain of DNAJB6b was critical for preventing tau aggregation. Moreover, reduced DNAJB6 expression and increased tau aggregation were detected in an age-dependent manner in immunohistochemical analysis of the hippocampus tissues of a mouse model of tau pathology. CONCLUSIONS: In summary, downregulation of DNAJB6b increases the insoluble form of tau, while overexpression of DNAJB6b reduces tau aggregation. Moreover, DNAJB6b associates with tau. Therefore, this study reveals that DNAJB6b is a direct sensor for its client tau in the HSP70 folding system in neuronal cells, thus helping to prevent AD.

Nursing students' emotions, educational concerns, and the impact of study careers and professional futures during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: COVID-19 is a challenge to education systems worldwide. The aim of the study was to explore the impact of COVID-19-pandemic-related emotions and COVID-19-related concern for education on the study careers and professional futures of nursing students. METHODS: The study was completed between March and June 2023 using a multi-stage sampling design. A total of 1126 nursing students were recruited to complete the questionnaire. The self-administered questionnaire consisted of basic characteristics of the subjects, the COVID-19-pandemic-related emotions scale, the COVID-19-related concern for education scale, and the impact of the COVID-19 on study careers and professional futures scale (SCPFI-19 S). One-way ANOVA/t-test, correlation coefficient analysis, and hierarchical linear regression analysis were used to explore factors influencing changes in study careers and professional futures, and the relationship between COVID-19-pandemic-related emotions and COVID-19-related concern for education. RESULTS: Univariate analysis of variance indicated that residence, willingness, and whether to engage in nursing after graduation were related to SCPFI-19 S (P < 0.05). COVID-19-pandemic-related emotions and COVID-19-related concern for education were significantly and positively associated with SCPFI-19 S (r = 0.566, P < 0.01; r = 0.199, P < 0.01). Stratified multiple regression analysis showed that COVID-19-pandemic-related emotions and COVID-19-related concern for education of nursing students were significant predictors of SCPFI-19 S. CONCLUSION: Overall, both COVID-19-pandemic-related emotions and COVID-19-related concern for education were significantly correlated with SCPFI-19 S. In future interventions, schools should consider structures and strategies to support students' mental health and educational trajectories during current and future epidemics or similar crises.

Sparse clusterability: testing for cluster structure in high dimensions.

BACKGROUND: Cluster analysis is utilized frequently in scientific theory and applications to separate data into groups. A key assumption in many clustering algorithms is that the data was generated from a population consisting of multiple distinct clusters. Clusterability testing allows users to question the inherent assumption of latent cluster structure, a theoretical requirement for meaningful results in cluster analysis. RESULTS: This paper proposes methods for clusterability testing designed for high-dimensional data by utilizing sparse principal component analysis. Type I error and power of the clusterability tests are evaluated using simulated data with different types of cluster structure in high dimensions. Empirical performance of the new methods is evaluated and compared with prior methods on gene expression, microarray, and shotgun proteomics data. Our methods had reasonably low Type I error and maintained power for many datasets with a variety of structures and dimensions. Cluster structure was not detectable in other datasets with spatially close clusters. CONCLUSION: This is the first analysis of clusterability testing on both simulated and real-world high-dimensional data.

TargetMine 2022: a new vision into drug target analysis.

SUMMARY: We introduce the newest version of TargetMine, which includes the addition of new visualization options; integration of previously disaggregated functionality; and the migration of the front-end to the newly available Bluegenes service. AVAILABILITY AND IMPLEMENTATION: TargeteMine is accessible online at https://targetmine.mizuguchilab.org/bluegenes. Users do not need to register to use the software. Source code for the different components listed in the article is available from TargetMine's organizational account at http://github.com/targetmine. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Essential Role of Social Context and Self-Efficacy in Daily Paretic Arm/Hand Use After Stroke: An Ecological Momentary Assessment Study With Accelerometry.

OBJECTIVE: To determine the momentary effect of social-cognitive factors, in addition to motor capability, on post-stroke paretic arm/hand use in the natural environment. DESIGN: A 5-day observational study in which participants were sent 6 Ecological Momentary Assessment (EMA) prompts/day. SETTING: Participants' daily environment. PARTICIPANTS: Community-dwelling, chronic stroke survivors with right-dominant, mild-moderate upper extremity paresis (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time duration of bimanual and unimanual paretic arm/hand use indexed by accelerometry; social-cognitive factors (social context, self-efficacy, mood) captured by EMA; motor capability of the paretic limb measured by Fugl-Meyer Upper Extremity Motor Assessment (FM). RESULTS: After accounting for participants' motor capability, we found that momentary social context (alone or not) and self-efficacy significantly predicted post-stroke paretic arm/hand use behavior in the natural environment. When participants were not alone, paretic arm/hand movement increased both with and without the less-paretic limb (bimanual and unimanual movements, P=.018 and P<.001, respectively). Importantly, participants were more likely to use their paretic arm/hand (unimanually) if they had greater self-efficacy for limb use (P=.042). EMA repeated-measures provide a real-time approach that captures the natural dynamic ebb and flow of social-cognitive factors and their effect on daily arm/hand use. We also observed that people with greater motor impairments (FM<50.6) increase unimanual paretic arm/hand movements when they are not alone, regardless of motor capability. CONCLUSIONS: In addition to motor capability, stroke survivors' momentary social context and self-efficacy play a role in paretic arm/hand use behavior. Our findings suggest the development of personalized rehabilitative interventions which target these factors to promote daily paretic arm/hand use. This study highlights the benefits of EMA to provide real-time information to unravel the complexities of the biopsychosocial (ie, motor capability and social-cognitive factors) interface in post-stroke upper extremity recovery.

Nursing students' emotional empathy, emotional intelligence and higher education-related stress: a cross-sectional study.

BACKGROUND: Nursing is one of the critically important disciplines in healthcare. Due to its complexity and specificity, nursing students often face additional higher education-related stress. However, there is less research on higher education-related stress among nursing students. Therefore, the purpose of this study was to investigate the effects of emotional empathy and emotional intelligence on the dimensions of higher education-related stress among nursing students. METHODS: This study utilized a multi-stage sampling design and was completed within the March-June 2023 period. A total of 1126 nursing students were recruited to complete the questionnaire. The self-administered questionnaire included the basic characteristics of the subjects, an emotional empathy scale, an emotional intelligence scale, and a higher education-related stress scale. One-way ANOVA/t-tests, correlation coefficients, and hierarchical linear regression analyses were used to explore the factors affecting higher education-related stress and the relationship between emotional empathy and emotional intelligence with the dimensions of higher education-related stress. RESULTS: The mean (SD) scores of challenges and dissatisfaction dimensions of higher education-related stress among nursing students were 30.052 (7.466) and 8.270 (2.205), respectively. Emotional empathy was significantly and positively related to the challenges and dissatisfaction dimensions of higher education-related stress. Emotional intelligence was negatively correlated with the challenges dimension of higher education-related stress and positively correlated with the dissatisfaction dimension. Stratified multiple regression analyses revealed that nursing students' emotional empathy and emotional intelligence were significant predictors of the dimensions of higher education-related stress. CONCLUSION: Overall, emotional empathy and emotional intelligence were significantly correlated with all dimensions of higher education-related stress. Consequently, in future interventions, the Chinese government and education sector can develop nursing students' ability to use emotional empathy and emotional intelligence rationally through emotional regulation strategies and emotional intelligence courses, to reduce the higher education-related stress they experience.

Efficient thermal treatment of radish (Raphanus sativus) for enhancing its bioactive compounds.

Old preserved radish (OPR), a traditional pickled-food of Asia, contains the healthy bioactive compounds, such as phenols and flavonoids. To preserve the phenols levels in radish by thermal treatment, which are decreased due to the polyphenol oxidase activity during long storage. Range of thermal processing evaluated to retain the maximum phenols level in the radish while processed at temperatures of 70 °C, 80 °C and 90 °C for 30 days. In this study, the bioactive compounds and antioxidant activity of thermal processing radish (TPR) were evaluated and compared with commercial products of OPR. Results showed the best condition of thermal processing, 80°C for 30 days, could increase the values of phenols, flavonoids and antioxidant activity that were 2.27, 2.74 and 2.89 times, respectively. When comparing the thermally processed radish or TPR with OPR, TPR has a higher content of phenols and flavonoids, indicating that the thermal processing was effective to increase the content of functional compounds in radish and significantly improved its nutritional values.

Lithium Bonds Enable Small Biomass Molecule-Based Ionoelastomers with Multiple Functions for Soft Intelligent Electronics.

Lipoic acid (LA), which originates from animals and plants, is a small biomass molecule and has recently shown great application value in soft conductors. However, the severe depolymerization of LA places a significant limitation on its utilization. A strategy of using Li-bonds as both depolymerization quenchers and dynamic mediators to melt transform LA into high-performance ionoelastomers (IEs) is proposed. They feature dry networks while simultaneously combining transparency, stretchability, conductivity, self-healing ability, non-corrosive property, re-mouldability, strain-sensitivity, recyclability, and degradability. Most of the existing soft conductors' drawbacks, such as the tedious synthesis, non-renewable polymer networks, limited functions, and single-use only, are successfully solved. In addition, the multi-functions allow IEs to be used as soft sensors in human-computer interactive games and wireless remote sports assistants. Notably, the recycled IE also provides an efficient conductive filler for transparent ionic papers, which can be used to design soft transparent triboelectric nanogenerators for energy harvesting and multidirectional motion sensing. This work creates a new direction for future research involving intelligent soft electronics.

Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate.

BACKGROUND: Bipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients. METHODS: Sixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale. RESULTS: BD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS. CONCLUSIONS: The study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.

Copper-Containing Polyoxometalate-Based Metal-Organic Framework as a Catalyst for the Oxidation of Silanes: Effective Cooperative Catalysis by Metal Sites and POM Precursor.

The oxidation of silanes into silanols is a very necessary transformation, and yet the rational fabrication of efficient catalysts for this reaction remains a challenging task. Here, a 3D polyoxometalate-based metal-organic framework (POMOF), [CuΙ3(pz)3{PMo12O40}]·H2O (HENU-8, HENU = Henan University; pz = pyrazine) was consciously prepared and first employed in the oxidation of dimethylphenylsilane with tert-butyl hydroperoxide (TBHP) as an oxidant, achieving 89% yield at a production rate of 132 mmol·g-1·h-1. Control experiments indicated that polyoxometalates and Cu atoms together affected the ultimate outcome in this catalytic system, and the designed catalyst followed a free radical mechanism.

Translational pathology, genomics and the development of systemic therapies for acral melanoma.

Acral melanomas arise on the non-hair bearing skin of the palms, soles and in the nail beds. These rare tumors comprise 2-3 % of all melanomas, are not linked to UV-exposure, and represent the most frequent subtype of melanomas in patients of Asian, African and Hispanic origin. Although recent work has revealed candidate molecular events that underlie acral melanoma development, this knowledge is not yet been translated into efficacious local, regional, or systemic therapies. In the current review, we describe the clinical characteristics of acral melanoma and outline the genetic basis of acral melanoma development. Further discussion is given to the current status of systemic therapy for acral melanoma with a focus on ongoing developments in both immunotherapy and targeted therapy for the treatment of advanced disease.

Comprehensive analysis of gut microbiota of a healthy population and covariates affecting microbial variation in two large Japanese cohorts.

BACKGROUND: Inter-individual variations in gut microbiota composition are observed even among healthy populations. The gut microbiota may exhibit a unique composition depending on the country of origin and race of individuals. To comprehensively understand the link between healthy gut microbiota and host state, it is beneficial to conduct large-scale cohort studies. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. RESULTS: A total of 1596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostridium, Parabacteroides, Prevotella_9, Roseburia, and Subdoligranulum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance. CONCLUSIONS: We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and specific dietary habit affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

Host-parasite interaction associated with major mental illness.

Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in host immune responses against T. gondii infection. Specifically, our cell biology and gene expression studies have revealed that DISC1 Leu607Phe variation, which changes DISC1 interaction with activating transcription factor 4 (ATF4), modifies gene expression patterns upon T. gondii infection. Our epidemiological data have also shown that DISC1 607 Phe/Phe genotype was associated with higher T. gondii antibody levels in sera. Although further studies are required, our study provides mechanistic insight into one of the few well-replicated serological observations in major mental illness.

Unusual Cerebral Aneurysm after Stereotactic Radiosurgery to Treat Trigeminal Neuralgia.

Stereotactic radiosurgery is a treatment option for trigeminal neuralgia. This procedure is minimally invasive, but tumor development and facial numbness have been reported. Here, we report an unusual presentation after stereotactic radiosurgery to treat trigeminal neuralgia. A 60-year-old man demonstrated typical signs for type 1 trigeminal nerve neuralgia and was treated with medication for 5 years. Owing to an intolerance to that medication, he received stereotactic radiosurgery with 66 Gy. During a 9-year follow-up exam, dizziness with a spinning sensation was reported and a right superior cerebellar thrombosed aneurysm was diagnosed. He received transarterial embolization with coiling of aneurysm and subsequently reported no complications on follow-up exams. Although stereotactic radiosurgery is a promising treatment for trigeminal neuralgia, aneurysm development may be considered a possible complication. Long-term follow-up care of these patients should be considered. To understand the relationship between radiosurgery and the potential development of a cerebral aneurysm, further research is needed.

Cerebral air embolism after percutaneous kyphoplasty: a rare case report.

Cerebral air embolism (CAE) is considered as a rare complication during the routine medical procedures in the literature review. We reported a very rare complication of CAE after the percutaneous kyphoplasty (PKP) for the treatment of acute vertebral compression fracture.

Mesenchymal Stem Cell-Derived Extracellular Vesicle: A Promising Alternative Therapy for Osteoporosis.

Osteoporosis is the chronic metabolic bone disease caused by the disturbance of bone remodeling due to the imbalance of osteogenesis and osteoclastogenesis. A large population suffers from osteoporosis, and most of them are postmenopausal women or older people. To date, bisphosphonates are the main therapeutic agents in the treatment of osteoporosis. However, limited therapeutic effects with diverse side effects caused by bisphosphonates hindered the therapeutic applications and decreased the quality of life. Therefore, an alternative therapy for osteoporosis is still needed. Stem cells, especially mesenchymal stem cells, have been shown as a promising medication for numerous human diseases including many refractory diseases. Recently, researchers found that the extracellular vesicles derived from these stem cells possessed the similar therapeutic potential to that of parental cells. To date, a number of studies demonstrated the therapeutic applications of exogenous MSC-EVs for the treatment of osteoporosis. In this article, we reviewed the basic back ground of EVs, the cargo and therapeutic potential of MSC-EVs, and strategies of engineering of MSC-EVs for osteoporosis treatment.

Evaluation of Class IIa Histone Deacetylases Expression and In Vivo Epigenetic Imaging in a Transgenic Mouse Model of Alzheimer's Disease.

Epigenetic regulation by histone deacetylase (HDAC) is associated with synaptic plasticity and memory formation, and its aberrant expression has been linked to cognitive disorders, including Alzheimer's disease (AD). This study aimed to investigate the role of class IIa HDAC expression in AD and monitor it in vivo using a novel radiotracer, 6-(tri-fluoroacetamido)-1-hexanoicanilide ([18F]TFAHA). A human neural cell culture model with familial AD (FAD) mutations was established and used for in vitro assays. Positron emission tomography (PET) imaging with [18F]TFAHA was performed in a 3xTg AD mouse model for in vivo evaluation. The results showed a significant increase in HDAC4 expression in response to amyloid-ß (Aß) deposition in the cell model. Moreover, treatment with an HDAC4 selective inhibitor significantly upregulated the expression of neuronal memory-/synaptic plasticity-related genes. In [18F]TFAHA-PET imaging, whole brain or regional uptake was significantly higher in 3xTg AD mice compared with WT mice at 8 and 11 months of age. Our study demonstrated a correlation between class IIa HDACs and Aßs, the therapeutic benefit of a selective inhibitor, and the potential of using [18F]TFAHA as an epigenetic radiotracer for AD, which might facilitate the development of AD-related neuroimaging approaches and therapies.