Clinical characteristics and antimicrobial susceptibility profiles of Mycobacterium abscessus and Mycobacterium massiliense pulmonary infection.

INTRODUCTION: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug susceptibility statuses of different Mycobacterium abscessus (MAB) subspecies. METHODS: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine vitro susceptibility of imipenem-relebactam, omadacycline, and other conventional antibiotics. Patient's clinical characteristics were collected and analysed. RESULTS: There were 139 M. abscessus, 39 M. massiliense, and 1 M. bolletii, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. Relebactam with imipenem resulted in a 2-fold reduction in the minimum inhibitory concentration (MIC) value compared to imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. CONCLUSIONS: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. Imipenem-relebactam and omadacycline are promising antibiotics for MABC infection treatment.

Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample ( N = 114, 9 - 17 years, M age = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds.

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevel-opmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds.

OBJECTIVE: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. METHODS: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). RESULTS: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. CONCLUSION: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. SIGNIFICANCE: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

Association between the frontoparietal network, clinical symptoms and treatment response in individuals with untreated anorexia nervosa.

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.

Aims: The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients. Methods: Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets. A PPK model was developed using the training group data. ML models were then established based on individual pharmacokinetic data derived from the PPK basic model. The prediction performances of the PPK-based ML model and Bayesian forecasting approach were compared using data from the test group. Results: The final PPK model, incorporating hematocrit and CYP3A5 genotypes as covariates, was successfully established. Individual predictions of TAC using the PPK basic model, postoperative date, CYP3A5 genotype, and hematocrit showed improved rankings in ML model construction. XGBoost, based on the TAC PPK, exhibited the best prediction performance. Conclusion: The PPK-based machine learning approach emerges as a superior option for predicting TAC concentrations in Chinese renal transplant recipients.

Morphological Integrated Preparation Method and Implementation of Inorganic/Organic Dual-Phase Composite Gradient Bionic Bone Scaffold.

Large bone defects caused by congenital deformities and acquired accidents are increasing day by day. A large number of patients mainly rely on artificial bone for repair. However, artificial bone cannot fully imitate the structure and composition of human bone, resulting in a large gap with autologous bone function. Therefore, this article proposes a continuous preparation method for inorganic/organic biphasic composite gradient biomimetic bulk bone scaffolds. First, a controllable gradient hybrid forming platform for inorganic/organic dual-phase biomaterials was constructed, and the feeding control strategy was studied to achieve precise control of the feeding of sodium alginate/gelatin composite organic materials and hydroxyapatite inorganic materials. The speed is, respectively, sent from the corresponding feeding nozzle to the mixing chamber to realize the uniform mixing of the biphasic material and the extrusion of the composite material, and the inorganic/organic biphasic composite gradient biomimetic bone scaffold with gradual structure and composition is prepared. Second, to prove the superiority of the preparation method, the physicochemical and biological properties of the prepared scaffolds were evaluated. The test results showed that the morphological characteristics of the biphasic composite gradient bone scaffold showed good microscopic porosity and the structure and composition showed gradients. The mechanical properties are close to that of human bone tissue and in vitro cell experiments show that the scaffold has good biocompatibility and bioactivity. In conclusion, this article provides a new type of bone scaffold preparation technology and equipment for the field of tissue engineering, which has research value and application prospects.

CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation.

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

MRI morphometry of the anterior and posterior cerebellar vermis and its relationship to sensorimotor and cognitive functions in children.

INTRODUCTION: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. METHODS: Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. RESULTS: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. CONCLUSIONS: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.

The role of THBS1 and PDGFD in the immune microenvironment of Helicobacter pylori-associated gastric cancer.

BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.

Polyvalent mpox mRNA vaccines elicit robust immune responses and confer potent protection against vaccinia virus.

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Oxidative stress contributes to hypermethylation of Histone H3 lysine 9 in placental trophoblasts from preeclamptic pregnancies.

Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.

Associations of Dietary Diversity Trajectories with Frailty among Chinese Older Adults: A Latent Class Trajectory Analysis Based on a CLHLS Cohort.

BACKGROUND: High dietary diversity has been found to be associated with frailty. However, the trajectory of dietary diversity intake in relation to frailty is unclear. METHODS: Using the latent class trajectory modeling approach, we identified distinctive dietary variety trajectory groups among 2017 participants based on the Chinese Longitudinal Healthy Longevity Survey acquired at four time points within a 10-year period. Frailty status was assessed using a frailty index comprising 37 health deficits. Dietary diversity was quantified using the dietary variety score (DVS), based on food category consumption frequency. Logistic regression analyses were employed to explore the association between DVS change trajectories and frailty. RESULTS: This study identified two distinct DVS trajectories: "Moderate-Slow decline-Slow growth", encompassing 810 (40.16%) individuals, and "Moderate-Slow growth-Accelerated decline", including 1207 (59.84%) individuals. After adjusting for covariates, the odds ratio for DVS in the "Moderate-Slow decline-Slow growth" group was 1.326 (95% confidence interval: 1.075-1.636) compared to the "Moderate-Slow growth-Accelerated decline" group. The "Moderate-Slow decline-Slow growth" trajectory continued to decrease and was maintained at a low level in the early stages of aging. CONCLUSION: Sustaining a high dietary diversity trajectory over time, particularly in the early stages of aging, could potentially decrease the risk of frailty among older Chinese adults.

Somatomotor-visual resting state functional connectivity increases after 2 years in the UK Biobank longitudinal cohort.

Purpose: Functional magnetic resonance imaging (fMRI) and functional connectivity (FC) have been used to follow aging in both children and older adults. Robust changes have been observed in children, in which high connectivity among all brain regions changes to a more modular structure with maturation. We examine FC changes in older adults after 2 years of aging in the UK Biobank (UKB) longitudinal cohort. Approach: We process fMRI connectivity data using the Power264 atlas and then test whether the average internetwork FC changes in the 2722-subject longitudinal cohort are statistically significant using a Bonferroni-corrected t-test. We also compare the ability of Power264 and UKB-provided, independent component analysis (ICA)-based FC to determine which of a longitudinal scan pair is older. Finally, we investigate cross-sectional FC changes as well as differences due to differing scanner tasks in the UKB, Philadelphia Neurodevelopmental Cohort, and Alzheimer's Disease Neuroimaging Initiative datasets. Results: We find a 6.8% average increase in somatomotor network (SMT)-visual network (VIS) connectivity from younger to older scans (corrected p<10-15) that occurs in male, female, older subject (>65 years old), and younger subject (<55 years old) groups. Among all internetwork connections, the average SMT-VIS connectivity is the best predictor of relative scan age. Using the full FC and a training set of 2000 subjects, one is able to predict which scan is older 82.5% of the time using either the full Power264 FC or the UKB-provided ICA-based FC. Conclusions: We conclude that SMT-VIS connectivity increases with age in the UKB longitudinal cohort and that resting state FC increases with age in the UKB cross-sectional cohort.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice.

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.

Association of per- and polyfluoroalkyl substances with constipation: The National Health and Nutrition Examination Survey (2005-2010).

BACKGROUND: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood. OBJECTIVE: This study seeks to explain the relationship between PFAS and constipation. METHODS: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables. RESULTS: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 µg/L) compared to those without constipation (23.30 µg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation. CONCLUSION: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation.