CDC73 serves as a tumour-promoting factor in oesophageal cancer.

The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both in vitro and in vivo. Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.

Ab Initio Density Functional Theory Calculation: Americium Hydrolysis Mechanism.

The hydrolysis mechanism of americium was calculated using density functional theory, and the detailed microscopic reaction mechanism was obtained. The results show that americium reacts with water along the octet state to produce oxides and H2, and that this reaction is exothermic. The interaction between Am and O atoms gradually changes from initially electrostatic interaction to covalent interaction, and continues to strengthen. During the reaction process, Am atoms always lose electrons, the 5f orbital is obviously involved, and there is df orbital hybridization. This study provides the necessary theoretical data support for the theoretical and experimental study of the actinide system.

High-Resolution Rovibronic Cross Sections of the MgH+ Molecular Cation.

The high-resolution rovibronic line lists of the MgH+ molecular cation are presented in our work. The potential energy curves are calculated by the method of multireference configuration interaction and Davidson correction (MRCI+Q) with the spin-orbit coupling (SOC) effect. Spectroscopy constants are fitted and the results are in good agreement with experiments, ensuring the accuracy of the electronic structure. On account of potential energy curves and transition dipole moments, the Franck-Condon factors and Einstein coefficients of transition are obtained. These calculations are used to obtain an accurate partition functions and line lists for molecules. Using the partition functions and line lists, the absorption cross-sections under different temperatures and pressures were simulated. Our work could provide some theoretical insights into solar and cold planet spectrum.

Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury.

Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.

Synthesis of a COF-on-MOF hybrid nanomaterial for enhanced colorimetric biosensing.

The construction of hybrid materials is significant for the exploration of functionalities in colorimetric biosensing due to its structural designability and synergy effects. In this work, a COF-on-MOF hybrid nanomaterial has been newly synthesized for colorimetric biosensing. Experimental results reveal that on-surface synthesis of COF on MOF brings nanoscale proximity between COF and MOF, which exhibits more than two folds of peroxidase-like activity as compared to single Fe-MOF. Therefore, by using the MCA@Fe-MOF nanomaterial with the assist of a specific acetyl-peptide, MCA@Fe-MOF can serve as an efficient signal reporter for colorimetric assay of histone deacetylase (HDAC), and the limit of detection (LOD) can be as low as 0.261 nM. Looking forward, the demand for diverse and promising COF-on-MOF nanomaterials with varied functionalities is anticipated, propelling further exploration of their role in colorimetric biosensing.

Structure elucidation and antioxidant activity of a polysaccharide from Penthorum chinense Pursh.

Penthorum chinense Pursh is a traditional Miao medicine, mainly used in the treatment of liver diseases. In this study, an acidic heteropolysaccharide PCPP was isolated from P. chinense with an average molecular weight of 14.96 kDa. PCPP contained arabinogalactan and homogalacturonan segments, which is formed by 4-Galp-(1 â†’ 5)-Araf-1 and 3,6-Galp-(1 â†’ 6)-Galp-1,3 glycosidic linkage. A variety of side chains, including t-Glcp-(1 â†’ 4)-Glcp-(1 â†’ 4)-GlcpA-1, t-Xylp-(1→, and 2-Manp-(1 â†’ 4)-GalpA-1,3 linked to the O-3 and O-6 of 3,6-Galp. The antioxidant activity measurement in three models demonstrated that PCPP exhibited ROS scavenging capacity, antioxidant ability in the cellular model, enhancement of oxidative stress resistance, and healthspan-promoting effect in the worm model. These results provided the theoretical fundament of PCPP as a potential natural antioxidant.

Precisely Engineering Asymmetric Atomic CoN4 by Electron Donating and Extracting for Oxygen Reduction Reaction.

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling.

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAV-VEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

Development and external validation of a prediction model for digit replantation failure after traumatic amputations based on a prospective multicenter cohort.

BACKGROUND: Failure of digit replantation after traumatic amputation is difficult to predict. The authors aimed to develop a prognostic model to better identify factors that better predict replantation failure following traumatic digit amputation. MATERIALS AND METHODS: In this multicenter prospective cohort, the authors identified patients who had received digit replantation between 1 January 2015 and 1 January 2019. Univariable and multivariable analyses were performed successively to identify independently predictive factors for failure of replanted digit. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. This model was then internally validated with bootstrap resampling and further externally validated in validation cohort. RESULTS: Digit replantation was failed in 101 of 1062 (9.5%) digits and 146 of 1156 digits (12.6%) in the training and validation cohorts, respectively. The authors found that six independent prognostic variables were associated with digit replantation failure: age, mechanism of injury, ischemia duration, smoking status, amputation pattern (complete or incomplete), and surgeon's experience. The prediction model achieved good discrimination, with concordance indexes of 0.81 (95% CI: 0.76-0.85) and 0.70 (95% CI: 0.65-0.74) in predicting digit failure in the training and validation cohorts, respectively. Calibration curves were well-fitted for both training and validation cohorts. CONCLUSIONS: The proposed prediction model effectively predicted the failure rate of digit replantation for individual digits of all patients. It could assist in selecting the most suitable surgical plan for the patient.

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring-and therefore more extensively studied-malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care.

Efficacy of EDTA-NS irrigation in eradicating Staphylococcus aureus biofilm-associated infection.

Aims: To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. Methods: EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection. Results: When 10 mM or higher EDTA-NS concentrations were used for ten minutes, over 99% of S. aureus biofilm formed on all three types of materials was eradicated in terms of absorbance measured at 595 nm and colony-forming units (CFUs) after culturing. Consistently, SEM and CSLM scanning demonstrated that less adherence of S. aureus could be observed on all three types of materials after 10 mM EDTA-NS irrigation for ten minutes. In the rat model, compared with NS irrigation combined with rifampin (Ti-6Al-4V wire-implanted rats: 60% bacteria survived; HXLPE particle-implanted rats: 63.3% bacteria survived), EDTA-NS irrigation combined with rifampin produced the highest removal rate (Ti-6Al-4V wire-implanted rats: 3.33% bacteria survived; HXLPE particle-implanted rats: 6.67% bacteria survived). In the pig model, compared with NS irrigation combined with rifampin (Ti-6Al-4V plates: 75% bacteria survived; HXLPE bearings: 87.5% bacteria survived), we observed a similar level of biofilm disruption on Ti-6Al-4V plates (25% bacteria survived) and HXLPE bearings (37.5% bacteria survived) after EDTA-NS irrigation combined with rifampin. The in vivo study revealed that the biomass of S. aureus biofilm was significantly reduced when treated with rifampin following irrigation and debridement, as indicated by both the biofilm bacterial burden and crystal violet staining. EDTA-NS irrigation (10 mM/10 min) combined with rifampin effectively removes S. aureus biofilm-associated infections both in vitro and in vivo. Conclusion: EDTA-NS irrigation with or without antibiotics is effective in eradicating S. aureus biofilm-associated infection both ex and in vivo.

Jianpi Antai formula prevents miscarriage by repressing M1 polarization of decidual macrophages through ubiquitination of NLRP3 mediated by MARCH7.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Antai Formula (JAF) is an ancient formula from He's gynecology, which has been used clinically for more than 30 years and has significant therapeutic effects on spontaneous abortion (SA). Both macrophage polarization and NLRP3 inflammasome correlate with the occurrence of SA in women with recurrent or threatened miscarriage. Whether JAF prevent SA via mediating activation of decidual macrophage (dMφ) and ubiquitination-associated degradation of NLRP3 remains uncertain. AIM OF THE STUDY: This study aimed to clarify the effects of JAF on pregnancy outcomes and dMφ polarization at the maternal-fetal interface in an SA mouse model, and use in vivo and invitro methods to explore whether JAF can inhibit M1 polarization of dMφ by up-regulating MARCH7-mediated NLRP3 ubiquitination, thereby preventing SA. MATERIALS AND METHODS: The CBA/J × DBA/2 mating method was used to establish an SA model and the dMφs of SA mice were isolated and cultured. Th1-, Th2-, Th17- and Treg-related cytokine levels were evaluated using ELISA. qRT-PCR was used to detect the levels of M1/M2 macrophage-related cytokine mRNA in the decidua, and western blotting was used to detect the expression of NLRP3 inflammasome-related proteins in the decidua and placenta. The expression of M1/M2 markers of dMφ was detected using flow cytometry, ASC speck formation was observed using immunofluorescence, and the ubiquitination level of MARCH7-NLRP3 was detected using co-immunoprecipitation. RESULTS: JAF increased the survival rate of fetuses and the levels of estradiol and progesterone in SA model mice. It also reduced the serum Th1 and Th17-associated cytokine levels and decidual M1 macrophage-associated cytokine levels, while elevating the M2 macrophages in SA mice. NLRP3, caspase-1, ASC, and IL-1ß protein expression in the decidua and placenta were also reduced. si-MARCH7 transfection reversed the effect of JAF on inhibiting the formation of the NLRP3 inflammasome and the activation of macrophages in dMφs of SA mice. CONCLUSION: JAF could effectively prevent and treat SA by repressing M1 polarization of dMφs through NLRP3 ubiquitination and pyroptosis inhibition, which were mediated by MARCH7.

Epigenetic Aging Is Associated With Measures of Midlife Muscle Volume and Attenuation in CARDIA Study.

BACKGROUND: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with age-related diseases including cancer and cardiovascular diseases. However, the associations between GAA and muscle mass and function are unknown. METHODS: We estimated measures of GAA in 1 118 Black and White participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at exam years (Y) 15 (2000-2001) and 20 (2005-2006). Abdominal muscle composition was measured using CT scans at the Y25 (2010-2011) visit. We used multivariate regression models to examine associations of GAA estimates with muscle imaging measurements. RESULTS: In the CARDIA study, each 1-year higher GAA was associated with an average 1.1% (95% confidence interval [CI]: 0.6%, 1.5%) higher intermuscular adipose tissue (IMAT) volume for abdominal muscles. Each 1-year higher GAA was associated with an average -0.089 Hounsfield unit (HU; 95% CI: -0.146, -0.032) lower lean muscle attenuation and an average -0.049 HU (95% CI: -0.092, -0.007) lower IMAT attenuation for abdominal muscles. Stratified analyses showed that GAA was more strongly associated with higher abdominal muscle IMAT volume in females and significantly associated with lower lean muscle attenuation for White participants only. CONCLUSIONS: Higher GAA is associated with higher abdominal muscle IMAT volume and lower lean muscle attenuation in a midlife population.

The development of commitment: Attention for intention.

Adhering to a partially defined plan requires an intentional commitment that curbs distracting desires conflicting with the planned course of action, enabling humans to act coherently over time. Two studies (N = 50, 27 girls, ages 5-6, Han Chinese, in Hangzhou, China, 2022.02-2022.03) explored the development of commitment to partial plans in a sequential decision-making task and the underlying cognitive capacity focusing on its correlation to attentional control. Results suggest that only 6-year-olds committed to partial plans (d = .51), and children's commitment ratio was positively correlated with the use of proactive control (r = .40). These findings indicate that intentional commitment does not develop simultaneously with intention understanding, but rather matures gradually with the development of attentional control.

Development and evaluation of a program based on a generative pre-trained transformer model from a public natural language processing platform for efficiency enhancement in post-procedural quality control of esophageal endoscopic submucosal dissection.

BACKGROUND: Post-procedural quality control of endoscopic submucosal dissection (ESD) is emphasized in guidelines. However, this process can be tedious and time-consuming. Recently, a pre-training model called generative pre-trained transformer (GPT) on a public natural language processing platform has emerged and garnered significant attention, whose capabilities align well with the post-procedural quality control process and have the potential to streamline it. Therefore, we developed a simple program utilizing this platform and evaluated its performance. METHODS: Esophageal ESDs were retrospectively included. The manual quality control process was performed and act as reference standard. GPT's prompt was optimized through multiple iterations. A Python program was developed to automatically submit prompt with pathological report of each ESD procedure and collect quality control information provided by GPT. Its performance on quality control was evaluated with accuracy, precision, recall, and F-1 score. RESULTS: 165 cases were involved into the dataset, of which 5 were utilized as the prompt optimization dataset and 160 as the validation dataset. Definitive prompt was achieved through seven iterations. Time spent on the validation dataset by GPT was 13.47 ± 2.43 min. Accuracies of pathological diagnosis, invasion depth, horizontal margin, vertical margin, vascular invasion, and lymphatic invasion of the quality control program were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), 0.931, 1.0, and 1.0, respectively. Precisions were (0.965, 0.969) (95% CI), (0.934, 0.954) (95% CI), and 0.957 for pathological diagnosis, invasion depth, and horizontal margin, respectively. Recalls were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), and 0.931 for factors as mentioned, respectively. F1-score were (0.945, 0.957) (95% CI), (0.928, 0.948) (95% CI), and 0.941 for factors as mentioned, respectively. CONCLUSIONS: This quality control program was qualified of post-procedural quality control of esophageal ESDs. GPT can be easily applied to this quality control process and reduce workload of the endoscopists.

Theoretic Study of Sulfur-Doped Graphdiynes by X-ray Spectroscopy.

Sulfur-doped graphdiyne at different sites has a tremendous impact on its electronic structure and properties. Due to the large number of S-doping sites, there is no comprehensive and systematic experimental and theoretical study regarding the identification of S-doped graphdiyne configurations. In this paper, X-ray photoelectron (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectra as well as geometries of 10 sulfur-doped graphdiyne molecules have been simulated at the density functional theory (DFT) level. Different types of carbon spectra were theoretically modeled to analyze the contribution of the spectra. Calculated results show that the NEXAFS spectra exhibit a clear dependence on the local structure. The theoretically simulated XPS spectra are in good agreement with the experimental spectra. The XPS spectra combined with the NEXAFS spectra can provide effective information for identifying the 10 S-doped conformations. Our research results provide further theoretical prediction and guidance for the experimental synthesis of S-doped graphdiyne, which solves the difficult problem of identification of S-doped carbon-based materials.

Evaluation of the correlation between fetuin-B levels and essential hypertension: a cross-sectional study.

Background: Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension. Method: A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension and 180 age- and-sex-matched healthy subjects were enrolled. Plasma fetuin-B, endothelin 1 (ET-1), nitric oxide (NO), and adiponectin (ADI) levels were measured using ELISA kits. Results: Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure, body mass index, fat percentage in vivo, waist-hip ratio, intima-media thickness, low-density lipoprotein cholesterol (LDL-C), glutamyltranspeptidase, alanine transaminase, albumin, fasting blood glucose (FBG), glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (all P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (odds ratio: 1.060, 95% CI: 1.034-1.086, P < 0.001). Receiver operating characteristic curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 µg/mL (sensitivity 77.4%, specificity 63.3%) (area under the curve) = 0.7738, 95% CI 0.7276-0.8200, P < 0.001). Conclusion: Elevated fetuin-B levels are associated with an increased risk of essential hypertension.

Problematic Internet Use in Early Adolescents: Gender and Loneliness Differences in a Latent Growth Model.

Purpose: Based on the Cognitive-Behavioral model and the Interaction of Person-Affect-Cognition-Execution model, this study examined the developmental trajectory of problematic Internet use (PIU) in early adolescents and explored whether there were gender differences in the onset level and rate of development of this developmental trajectory, and tested whether developmental changes in loneliness could have an impact on the developmental trajectory of problematic Internet use. Participants and Methods: This longitudinal study collected data on PIU and loneliness from 296 early adolescents (Mage=11.65, SD=0.58) in four waves. The development of PIU in adolescents and the effects of gender and loneliness development on PIU development were examined using a latent growth model. Results: The results revealed that individuals' PIU development showed a nonlinear latent growth model, with PIU significantly higher than 0 in grade 6 and its growth rate slowing down as PIU increased. Individuals' PIU at low starting levels developed more rapidly later. Boys had higher initial levels of PIU but their PIU developed and increased at the same rate as girls'. Both the initial value and slope of loneliness had a significant effect on the initial value and slope of boys' and girls' PIU. Conclusion: Interventions for PIU in early adolescents also need to consider loneliness at the same time, and intervention groups can focus on individuals with low initial levels of PIU, boys, and individuals with high levels of loneliness.

Associations between GrimAge acceleration and pulmonary function in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Background: The objective of this research was to determine whether pulmonary function is associated with epigenetic aging (GrimAge) and whether GrimAge predicts emphysema. Methods: This prospective study examined 1042 participants enrolled as part of a community-based longitudinal cohort. The cross-sectional associations between pulmonary function and GrimAge, measured at study year (Y) 20 (participant ages 40-45 years), and prospective associations with emphysema at Y25 were examined. Results: At Y20, forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) were negatively associated with GrimAge; for Y0-Y10 cumulative measures, only the FEV1/FVC ratio was associated with GrimAge at Y15 and Y20. Emphysema at Y25 was associated with GrimAge at Y15 and Y20. Conclusion: Pulmonary function was associated with GrimAge during early and mid-life; GrimAge partially mediated the association between pulmonary function and emphysema.