PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylation-Dependent Proteasomal Degradation.

Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a central protein in necroptosis, but posttranslational processes that regulate RIP3 activity and stability remain poorly understood. Here, we identify pellino E3 ubiquitin protein ligase 1 (PELI1) as an E3 ligase that targets RIP3 for proteasome-dependent degradation. Phosphorylation of RIP3 on T182 leads to interaction with the forkhead-associated (FHA) domain of PELI1 and PELI1-mediated K48-linked polyubiquitylation of RIP3 on K363. This same phosphorylation event is also important for RIP3 kinase activity; thus, PELI1 preferentially targets kinase-active RIP3 for degradation. PELI1-mediated RIP3 degradation effectively prevents cell death triggered by RIP3 hyperactivation. Importantly, upregulated RIP3 expression in keratinocytes from toxic epidermal necrolysis (TEN) patients is correlated with low expression of PELI1, suggesting that loss of PELI1 may play a role in the pathogenesis of TEN. We propose that PELI1 may function to control inadvertent activation of RIP3, thus preventing aberrant cell death and maintaining cellular homeostasis.

Substantially Accelerated Response and Recovery in Pd-Decorated WO3 Nanorods Gasochromic Hydrogen Sensor.

The development of hydrogen (H2) gas sensors is essential for the safe and efficient adoption of H2 gas as a clean, renewable energy source in the challenges against climate change, given its flammability and associated safety risks. Among various H2 sensors, gasochromic sensors have attracted great interest due to their highly intuitive and low power operation, but slow kinetics, especially slow recovery rate limited its further practical application. This study introduces Pd-decorated amorphous WO3 nanorods (Pd-WO3 NRs) as an innovative gasochromic H2 sensor, demonstrating rapid and highly reversible color changes for H2 detection. In specific, the amorphous nanostructure exhibits notable porosity, enabling rapid detection and recovery by facilitating effective H2 gas interaction and efficient diffusion of hydrogen ions (H+) dissociated from the Pd nanoparticles (Pd NPs). The optimized Pd-WO3 NRs sensor achieves an impressive response time of 14 s and a recovery time of 1 s to 5% H2. The impressively fast recovery time of 1 s is observed under a wide range of H2 concentrations (0.2-5%), making this study a fundamental solution to the challenged slow recovery of gasochromic H2 sensors.

A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient.

Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.

Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2.

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.

COVID-19 cases in US counties: roles of racial/ethnic density and residential segregation.

OBJECTIVE: To investigate how racial/ethnic density and residential segregation shape the uneven burden of COVID-19 in US counties and whether (if yes, how) residential segregation moderates the association between racial/ethnic density and infections. DESIGN: We first merge various risk factors from federal agencies (e.g. Census Bureau and Centers for Disease Control and Prevention) with COVID-19 cases as of June 13th in contiguous US counties (N = 3,042). We then apply negative binomial regression to the county-level dataset to test three interrelated research hypotheses and the moderating role of residential segregation is presented with a figure. RESULTS: Several key results are obtained. (1) Counties with high racial/ethnic density of minority groups experience more confirmed cases than those with low levels of density. (2) High levels of residential segregation between whites and non-whites increase the number of COVID-19 infections in a county, net of other risk factors. (3) The relationship between racial/ethnic density and COVID-19 infections is enhanced with the increase in residential segregation between whites and non-whites in a county. CONCLUSIONS: The pre-existing social structure like residential segregation may facilitate the spread of COVID-19 and aggravate racial/ethnic health disparities in infections. Minorities are disproportionately affected by the novel coronavirus and focusing on pre-existing social structures and discrimination in housing market may narrow the uneven burden across racial/ethnic groups.

Duration of Vasodilatory Action After Intra-arterial Infusions of Calcium Channel Blockers in Animal Model of Cerebral Vasospasm.

BACKGROUND: In medically refractory vasospasm, invasive intervention may be required. A commonly used approach is intra-arterial (IA) drug infusion. Although calcium channel blockers (CCBs) have been widely applied in this setting, studies comparing their efficacies and durations of action have been few. This study was performed to compare attributes of three CCBs (nicardipine, nimodipine, and verapamil), focusing on duration of the vasodilatory action based on angiography. METHODS: Vasospasm was produced in New Zealand white rabbits (N = 22) through experimentally induced subarachnoid hemorrhage and confirmed in each via conventional angiography, grouping them by IA-infused drug. After chemoangioplasty, angiography was performed hourly for 5 h to compare dilated and vasospastic arterial diameters. Drug efficacy, duration of action, and changes in mean arterial pressure (relative to baseline) were analyzed by group. RESULTS: Effective vasodilation was evident in all three groups immediately after IA drug infusion. The vasodilative effects of nimodipine and nicardipine peaked at 1 h and were sustained at 2 h, returning to initial vasospastic states at 3 h. In verapamil recipients, effects were more transient by comparison, entirely dissipating at 1 h. Only the nicardipine group showed a significant 3-h period of lowered blood pressure. CONCLUSIONS: Although nimodipine and nicardipine proved longer acting than verapamil in terms of vasodilation, their effects were not sustained beyond 2 h after IA infusion. Further study is required to confirm the vasodilatory duration of IA CCB based on perfusion status, and an effort should be made to find new alternative to extend the duration.

Coronavirus Disease 19 (COVID-19) complicated with pneumonia in a patient with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs.

In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.

Comparison of Posterior Cruciate-Retaining and High-Flexion Cruciate-Retaining Total Knee Arthroplasty Design.

BACKGROUND: High-flexion prostheses have been developed to achieve deep flexion after total knee arthroplasty. The purpose of this study is to compare standard NexGen (CR, cruciate-retaining) and high-flexion NexGen (CR-flex) total knee prostheses in terms of range of motion, clinical and radiologic outcomes, rates of complications, and survivorship in long-term follow-up. METHODS: From January 2000 to December 2008, 423 consecutive knees underwent total knee arthroplasty using standard CR or CR-flex prostheses. Fifty-three patients were lost to follow-up or declined to participate and 54 died, leaving 290 knees. The minimum duration of follow-up was 8 years (mean 10.1 years). Physical examination and knee scoring of patients were assessed preoperatively, at 6 months and 1 year after surgery, and annually thereafter. Supine anteroposterior and lateral radiographs and standing anteroposterior hip-to-ankle radiographs were obtained preoperatively and at each follow-up. RESULTS: Mean postoperative range of motions in the standard CR group and the CR-flex group were similar, showing no significant difference between the 2 groups (P = .853). At the time of the final follow-up, mean total Hospital for Special Surgery scores were similar between the 2 groups (P = .118). Mean Knee Society pain (P = .325) and function scores (P = .659) were also comparable between the 2 groups. Western Ontario and McMaster Universities Osteoarthritis Index score showed no intergroup difference either (P = .586). The mean hip-knee-ankle angle at the final follow-up was approximately the same (P = .940). Mean coronal angles of femoral and tibial component at final follow-up were also similar (P = .211 and P = .764, respectively). The prevalence of the radiolucent line was 0.6% in the standard CR group and 0.9% in the CR-flex group. Estimated survival rate according to Kaplan-Meier survival analysis was 97.2% in the standard CR group and 95.6% in the CR-flex group at mean follow-up of 10.1 years. CONCLUSION: This study suggests that excellent clinical and radiographic outcomes could be achieved with both standard and high-flexion CR total knee designs. High-flexion CR prosthesis did not show any advantages over the standard design.

Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations.

Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)-induced mutagenesis. In our study, we have identified a rare subset of treatment-naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment-induced hypermutagenesis. We conducted Whole-Exome Sequencing (WES), Whole-Transcriptome Sequencing (WTS), and Single-Cell Sequencing (SCS) of TMZ-naïve and post-TMZ-treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ-naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ-induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ-naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ-naïve and post-TMZ-treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.

Fractionated stereotactic radiosurgery for malignant gliomas: comparison with single session stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major concern. We aimed to investigate the clinical efficacy and safety of fractionated SRS (fSRS) versus single-session SRS (sSRS) for malignant gliomas. METHODS: We retrospectively reviewed 58 malignant glioma patients who underwent gamma knife SRS from January 2015 to December 2018. Forty-one underwent sSRS, and 17 underwent fSRS. Median dose for fSRS was 28 Gy (range 24-35 Gy), with a median dose of 6 Gy per fraction (range 5-7 Gy). Patients received 4 or 5 fractions on consecutive days. Median dose for sSRS was 18 Gy (range 11-25 Gy), with a median isodose of 50% (range 50-65%). Mean target volumes were 5.9 and 19.3 cc for sSRS and fSRS, respectively (p < 0.001, two-sided t test). RESULTS: After SRS, median progression-free survival (PFS) was 4.5 and 4.6 months (p = 0.58), and median overall survival (OS) was 12.7 and 12.6 months for sSRS and fSRS (p = 0.41), respectively (log-rank test). The incidence of clinically significant radiation necrosis was 20.5% (8/39) and 18.8% (3/16) for sSRS and fSRS, respectively (p = 1, Fisher's exact test). CONCLUSION: fSRS for malignant glioma conferred local control and survival comparable with conventional sSRS. The radiation necrosis incidence was comparable between groups when a parallel biological effective dose was administered to the larger target volumes in the fSRS group. fSRS can be a better alternative to sSRS if re-irradiation is considered for large malignant gliomas.

Is arachnoid cyst a static disease? A case report and literature review.

INTRODUCTION: The increasing use of intracranial imaging has led to more frequent diagnoses of arachnoid cysts (ACs). Although ACs are a frequent finding on neuroimaging in children, the prevalence and natural history of these cysts are not well defined. Most ACs may persist and remain asymptomatic throughout life and not require treatment. However, there have been some case reports of ACs that have become larger or smaller over time and, in rare cases, have even spontaneously resolved. It is the authors' practice to recommend serial neuroimaging in patients with asymptomatic sylvian ACs and not offer surgery to patients without symptoms, even in those with a relatively large cyst. CASE REPORT: The present article describes a case involving a 6-year-old boy with a large, asymptomatic AC in the left Sylvian fissure involving the temporo-frontal region, which resolved spontaneously during the 2-year follow-up period after initial diagnosis without any surgical intervention. Currently, at the 7-year follow-up, the patient has remained neurologically intact, attends school, and is symptom-free. CONCLUSION: Clinicians should be mindful of the possibility of spontaneous regression when encountering patients with asymptomatic and/or incidentally diagnosed sylvian ACs.

Intentional cyanoacrylate ingestion: A rare cause of delayed gastric perforation requiring gastric wedge resection.

Cyanoacrylate (LOCTITE® 401™) is a fast-acting adhesive available nationwide, with medical and household uses. Most cases of cyanoacrylate exposure are accidental and occur in children less than 5years old. Various routes of exposure have been reported including the dermal, oral, ocular, otic, nasal, and urethral routes; however, very few result in serious complication and mortality. Although a few cases of airway obstruction related to cyanoacrylate ingestion have been reported, intentional cyanoacrylate ingestion-induced gastrointestinal tract injury has scarcely been reported. In addition, there have been no reports of serious complications following intentional cyanoacrylate ingestion requiring surgical intervention. Herein, we report a case of intentional ingestion of cyanoacrylate in a 70-year-old man who required gastric wedge resection due to delayed gastric perforation.

Differential investments and opportunities: How do neighborhood conditions moderate the relationship between perceived housing discrimination and social capital?

Though the adverse consequences of perceived housing discrimination have been documented, little is known about whether such experience undermines one's social capital in a neighborhood and even less is about whether and how this relationship is altered by neighborhood features. We proposed a framework that simultaneously considers within-individual and between-neighborhood processes. We applied multilevel structural equation models to data from Philadelphia (n = 9987) and found that (a) perceived housing discrimination was negatively associated with one's social capital even after other confounders were considered, (b) this negative association could be partly explained by the proliferated daily stress and anxiety mechanisms, (c) differential exposures to neighborhood social disadvantage accounted for the variation in social capital across neighborhoods, and (d) the adverse association between perceived housing discrimination and social capital could be attenuated by neighborhood stability. The findings suggested that appropriate interventions should buffer the negative association of perceived housing discrimination with social capital.

Both nitric oxide and nitrite prevent homocysteine-induced endoplasmic reticulum stress and subsequent apoptosis via cGMP-dependent pathway in neuronal cells.

Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells. Surprisingly, non-cytotoxic NO (S-nitrosoglutathione) and nitrite markedly reduced Hcy-induced IRE1α phosphorylation, Xbp1 mRNA splicing, CHOP expression, and Annexin V-positive cells, indicating the cytoprotection of NO and nitrite against Hcy-induced ER stress and apoptosis. Moreover, inhibition of sGC/cGMP pathway abolished the cytoprotective effects of NO and nitrite, whereas cellular elevation of cGMP levels mimicked the cytoprotective actions of NO and nitrite. These findings provide the first evidence showing that both NO and nitrite can reduce ER stress and subsequent apoptosis via NO-sGC-cGMP pathway in neuronal cells and suggesting that NO and/or nitrite may have therapeutic value in the treatment of ER stress-associated neurodegenerative diseases.

Taking varenicline for smoking cessation: A rare cause of pulmonary thromboembolism with infarction.

Varenicline (Champix®, Chantix®) is a partial agonist of the α4ß2 nicotinic acetylcholine receptor (nAChR) and a full agonist of the α7 nAChR. It has been used for smoking cessation since 2006. Varenicline has been associated with adverse cardiovascular (CV) events, including myocardial infarction, which may be caused by activation of the α7 nAChR receptor that in turn stimulates parasympathetic output from the brainstem to the heart, release of catecholamines, and has a prothrombotic effect. However, among the adverse CV events, the issue related to the varenicline-induced pulmonary thromboembolism (PTE) has not being addressed. We report a case of PTE with pulmonary infarction presenting as right flank pain that resulted from the use of varenicline (the total score of adverse drug reaction probability scale, 6; probable association between varenicline and pulmonary PTE) in a patient without underlying CV disease and in whom low probability of PTE (Wells score was zero) was identified.

Glucose deprivation triggers protein kinase C-dependent ß-catenin proteasomal degradation.

Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of ß-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G1 transition and enhancement of the LC3-II protein levels, whereas ß-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3ß was unable to abolish the glucose deprivation-mediated ß-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3ß-independent protein degradation. Intriguingly, the inhibition of PKCα using a pharmacological inhibitor and transfection of siRNA for PKCα was observed to effectively block glucose deprivation-induced ß-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G1 population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3ß-independent protein degradation of ß-catenin, leading to autophagy.

RABA members act in distinct steps of subcellular trafficking of the FLAGELLIN SENSING2 receptor.

Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo-synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis.

Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability.

During endochondral ossification, a process that accounts for the majority of bone formation in vertebrates, hypertrophic chondrocytes display a greater susceptibility to apoptosis when compared to proliferating chondrocytes. However, the molecular mechanisms underlying this phenomenon remain unclear. Nkx3.2, a member of the NK class of homeoproteins, is initially expressed in chondrogenic precursor cells, and later, during cartilage maturation, its expression is restricted to proliferating chondrocytes. Here, we show that the nuclear factor kappa B (NF-kappaB) pathway is required for chondrocyte viability and that Nkx3.2 supports chondrocyte survival by constitutively activating RelA. Although signal-dependent NF-kappaB activation has been intensively studied, ligand-independent NF-kappaB activation is poorly understood. The data presented here support a novel ligand-independent mechanism of NF-kappaB activation, whereby Nkx3.2 recruits the RelA-IkappaBalpha heteromeric complex into the nucleus by direct protein-protein interactions and activates RelA through proteasome-dependent IkappaBalpha degradation in the nucleus. Furthermore, we demonstrate that stage-specific NF-kappaB activation, mediated by Nkx3.2, regulates chondrocyte viability during cartilage maturation.

Gender Differences in the Protective Role of Grandparenting in Dementia Risk.

OBJECTIVES: This study provides one of the first national longitudinal studies of the association between caring for grandchildren (i.e., grandparenting) and the risk of dementia in the United States, with a focus on gender-specific variations. METHODS: We estimated discrete-time event history models, drawing upon data from the Health and Retirement Study (2000-2016). The analytic sample included 10,217 community-dwelling White and Black grandparents aged 52 years and older at baseline. RESULTS: Noncoresident grandparenting was associated with a lower risk of dementia for both women and men compared to grandparents who did not take care of grandchildren. However, the cognitive advantage showed different patterns based on gender and the combination of care intensity and family structure. Grandmothers had a lower risk of dementia than noncaregiving grandmothers when providing a light level of noncoresident grandparenting, whereas grandfathers who provided intensive noncoresident grandparenting had a reduced risk of dementia compared to their noncaregiving counterparts. Grandparenting experiences within multigenerational households and skipped-generation households were not associated with dementia risk. DISCUSSION: Intergenerational caregiving plays a pivotal role in shaping cognitive health during later life; however, the impact is nuanced, depending on factors such as gender, care intensity, and family structure.

Neighborhood Features and Cognitive Function: Moderating Roles of Individual Socioeconomic Status.

INTRODUCTION: There is an interest in exploring the associations between neighborhood characteristics and individual cognitive function; however, little is known about whether these relationships can be modified by individual socioeconomic status, such as educational attainment and income. METHODS: Drawing from the 2010-2018 Health and Retirement Study, this study analyzed 10,621 older respondents (aged 65+) with a total of 33,931 person-waves. These respondents did not have dementia in 2010 and stayed in the same neighborhood throughout the study period. Cognitive function was measured with a 27-point indicator biennially, and neighborhood characteristics (i.e., walkability, concentrated disadvantage, and social isolation) were assessed in 2010. All analyses were performed in 2023. RESULTS: Cognitive function is positively associated with neighborhood walkability and negatively related to concentrated disadvantage, suggesting that exposures to these neighborhood characteristics have long-lasting impacts on cognitive function. Furthermore, individual socioeconomic status modifies the relationship between neighborhood characteristics and cognitive function. Compared with those graduating from college, respondents without a bachelor's degree consistently have lower cognitive function but the educational gap in cognitive function narrows with increases in walkability (b= -0.152, SE=0.092), and widens when neighborhood concentrated disadvantage (b=0.212, SE=0.070) or social isolation (b=0.315, SE=0.125) rises. The income gap in cognitive function shrinks with increases in walkability (b= -0.063, SE=0.027). CONCLUSIONS: The moderating role of socioeconomic status indicates that low-socioeconomic status older adults who also live in disadvantaged neighborhoods face a higher risk of poor cognitive function. Low-education and low-income aging adults may have the most to gain from investments to improve neighborhood characteristics.