The kinase Jnk2 promotes stress-induced mitophagy by targeting the small mitochondrial form of the tumor suppressor ARF for degradation.

Mitophagy is essential for cellular homeostasis, but how mitophagy is regulated is largely unknown. Here we found that the kinase Jnk2 was required for stress-induced mitophagy. Jnk2 promoted ubiquitination and proteasomal degradation of the small mitochondrial form of the tumor suppressor ARF (smARF). Loss of Jnk2 led to the accumulation of smARF, which induced excessive autophagy that resulted in lysosomal degradation of the mitophagy adaptor p62 at steady state. Depletion of p62 prevented Jnk2-deficient cells from mounting mitophagy upon stress. Jnk2-deficient mice displayed defective mitophagy, which resulted in tissue damage under hypoxic stress, as well as hyperactivation of inflammasomes and increased mortality in sepsis. Our findings define a unique mechanism of maintaining immunological homeostasis that protects the host from tissue damage and mortality.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Acute Changes in the Resting Brain Networks in Concussion Patients: Small-World Topology Perspective.

BACKGROUND: The acute changes that occur in the small-world topology of the brain in concussion patients remain unclear. Here, we investigated acute changes in the small-world organization of brain networks in concussion patients and their influence on persistent post-concussion symptoms. METHODS: Eighteen concussion patients and eighteen age-matched controls were enrolled in this study. All participants underwent computed tomography, magnetic resonance imaging (MRI), susceptibility weighted imaging, and blood oxygen level-dependent functional MRI. A complex network analysis method based on graph theory was used to calculate the parameters of small-world networks under different degrees of network sparsity. All subjects were evaluated using the Glasgow Coma Scale and Rivermead Postconcussion Symptom Questionnaire. RESULTS: Compared with the controls, the normalized cluster coefficient (γ) of whole brain networks in patients and the "small-world" index (σ) was slightly enhanced, whereas the standardized minimum path (λ) was slightly shorter. Whole brain effect (Eglobal) and local effect (Elocal) changes were not pronounced. Under the condition of minimum network sparsity (Dmin = 0.13), the numbers of nodes in the "right intraorbital superior frontal gyrus" (Anatomical Automatic Labeling, AAL26), right globus pallidus (AAL76), and bilateral temporal transverse gyrus (AAL79,80) in brain concussion patients were significantly lower. The numbers of nodes in the left subcapital lobe (AAL61) and left occipital gyrus (AAL51) were significantly higher, and the normalized cluster coefficients of the right intraorbital supraphalus (AAL26) and left posterior cingulate gyrus (AAL35) were significantly increased. The normalized clustering coefficients of the right triangular subfrontal gyrus (AAL55) (based on the normalized clustering coefficients of nodes in AAL14) and left sub-parietal lobes (AAL61) were significantly reduced. The mean local effects of nodes in the right intraorbital upper frontal gyrus (AAL26), left posterior cingulate gyrus (AAL35), and bilateral auxiliary motor cortex (AAL19, 20) were enhanced, whereas the mean local effects of the bilateral triangular inferior frontal gyrus (AAL13,14) and left insular cap (AAL11) were reduced (p < 0.05). CONCLUSIONS: The overall trend of network topology abnormalities in patients was random, and generalized and local functional abnormalities were seen. Changes in the function and affective circuitry of the resting default network were particularly pronounced in these patients, which we speculate may be one of the main drivers of the cognitive dysfunction and mood changes seen in concussion patients.

Abnormal Interherispheric Functional Connectivity in Acute Pericoronitis: A Resting-State MRI Study.

OBJECTIVE: Acute pericoronitis (AP) is a prevalent cause of odontogenic toothache which can significantly impact brain function. Previous research has predominantly concentrated on localized brain activity. However, the synergistic changes between brain hemispheres induced by toothache and resulting abnormal functional connectivity across the brain have not been comprehensively studied. METHODS: A total of 34 patients with AP and 34 healthy individuals, matched for age, sex, and education were recruited for this study. All participants underwent resting-state functional magnetic resonance imaging (rs-MRI) scans. The voxel mirror homotopic connectivity (VMHC) method was used to identify intergroup differences. Brain regions exhibiting statistically significant differences were selected as regions of interest for further functional connectivity analysis. The partial correlation method was utilized to assess the correlation between abnormal VMHC values in different regions and clinical parameters, with age and sex included as covariates. RESULTS: Patients with AP exhibited reduced VMHC values in the thalamus and elevated VMHC values in the inferior frontal gyrus compared with healthy controls. Subsequent functional connectivity analyses revealed extensive changes in functional networks, predominantly affecting the default, frontoparietal, cerebellar, and pain networks. CONCLUSION: Changes in functional patterns across these brain networks offer novel insights into the neurophysiological mechanisms underlying pain information processing.

The modulation and mechanism of probiotic-derived polysaccharide capsules on the immune response in allergic diseases.

Allergic diseases, derived from the dysregulation of immune tolerance mechanisms, have been rising in the last two decades. Recently, increasing evidence has shown that probiotic-derived polysaccharide capsules exhibit a protective effect against allergic diseases, involving regulation of Th1/Th2 balance, induction of differentiation of T regulatory cells and activation of dendritic cells (DCs). DCs have a central role in controlling the immune response through their interaction with gut microbiota via their pattern recognition receptors, including Toll-like receptors and C-type-lectin receptors. This review discusses the effects and critical mechanism of probiotic-derived polysaccharide capsules in regulating the immune system to alleviate allergic diseases. We first describe the development of immune response in allergic diseases and recent relevant findings. Particular emphasis is placed on the effects of probiotic-derived polysaccharide capsules on allergic immune response. Then, we discuss the underlying mechanism of the impact of probiotic-derived polysaccharide capsules on DCs-mediated immune tolerance induction.

Edible insects as ingredients in food products: nutrition, functional properties, allergenicity of insect proteins, and processing modifications.

Edible insect products contain high-quality protein and other nutrients, including minerals and fatty acids. The consumption of insect food products is considered a future trend and a potential strategy that could greatly contribute to meeting food needs worldwide. However, insect proteins have the potential to be allergenic to insect consumers. In this review, the nutritional value and allergy risk of insect-derived foods, and the immune responses elicited by insect allergens are summarized and discussed. Tropomyosin and arginine kinase are the most important and widely known insect allergens, which induce Th2-biased immune responses and reduced the activity of CD4+T regulatory cells. Besides, food processing methods have been effectively improving the nutrients and characteristics of insect products. However, limited reviews systematically address the immune reactions to allergens present in edible insect proteins following treatment with food processing technologies. The conventional/novel food processing techniques and recent advances in reducing the allergenicity of insect proteins are discussed in this review, focusing on the structural changes of allergens and immune regulation.

Construction of Models To Predict the Effectiveness of E-Waste Control through Capture of Volatile Organic Compounds and Metals/Metalloids Exposure Fingerprints: A Six-Year Longitudinal Study.

The significant health implications of e-waste toxicants have triggered the global tightening of regulation on informal e-waste recycling sites (ER) but with disparate governance that requires effective monitoring. Taking advantage of the opportunity to implement e-waste control in the Guiyu ER since 2015, we investigated the temporal variations in levels of oxidative DNA damage, 25 volatile organic compound metabolites (VOCs), and 16 metals/metalloids (MeTs) in urine in 918 children between 2016 and 2021 to demonstrate the effectiveness of e-waste control in reducing population exposure risks. The hazard quotients of most MeTs and levels of 8-hydroxy-2'-deoxyguanosine in children decreased significantly during this time, indicating that e-waste control effectively reduces the noncarcinogenic risks of MeT exposure and levels of oxidative DNA damage. Using mVOC-derived indexes as a feature, a bagging-support vector machine algorithm-based machine learning model was constructed to predict the extent of e-waste pollution (EWP). The model exhibited excellent performance with accuracies >97.0% in differentiating between slight and severe EWP. Five simple functions established using mVOC-derived indexes also had high accuracy in predicting the presence of EWP. These models and functions provide a novel human exposure monitoring-based approach for assessing e-waste governance or the presence of EWP in other ERs.

Why Do People Gain Belly Fat in Rural Areas? A Study of Urinary Metal(loid)s and Abdominal Obesity in China.

Obesity is prevalent in rural areas of China, and there are inconsistent findings regarding the association between metal(loid) exposure and the risk of obesity. Abdominal obesity (AOB), which reflects visceral fat abnormity, is a crucial factor in studying obesity-related diseases. We conducted a study measuring 20 urinary metal(loid)s, 13 health indicators, and the waist circumference (WC) in 1849 participants from 10 rural areas of China to investigate their relationships. In the single exposure models, we found that urinary chromium (Cr) was significantly associated with the odds of having AOB [adjusted odds ratio (OR) = 1.81 (95% confidence interval (CI): 1.24, 2.60)]. In the mixture exposure models, urinary Cr consistently emerged as the top contributor to AOB, while the overall effect of mixed metal(loid)s was positive toward the odds of having AOB [adjusted OR: 1.33 (95% CI: 1.00, 1.77)], as revealed from the quantile g-computation model. After adjusting for the effects of other metal(loid)s, we found that the elevation of apolipoprotein B and systolic blood pressure significantly mediated the association between urinary Cr and the odds of having AOB by 9.7 and 19.4%, respectively. Our results suggest that exposure to metal(loid)s is a key factor contributing to the prevalence of AOB and WC gain in rural areas of China.

Alteration of the allergenicity of cow's milk proteins using different food processing modifications.

Milk is an essential source of protein for infants and young children. At the same time, cow's milk is also one of the most common allergenic foods causing food allergies in children. Recently, cow's milk allergy (CMA) has become a common public health issue worldwide. Modern food processing technologies have been developed to reduce the allergenicity of milk proteins and improve the quality of life of patients with CMA. In this review, we summarize the main allergens in cow's milk, and introduce the recent findings on CMA responses. Moreover, the reduced effects and underlying mechanisms of different food processing techniques (such as heating, high pressure, γ-ray irradiation, ultrasound irradiation, hydrolysis, glycosylation, etc.) on the allergenicity of cow's milk proteins, and the application of processed cow's milk in clinical studies, are discussed. In addition, we describe the changes of nutritional value in cow's milk treated by different food processing technologies. This review provides an in-depth understanding of the allergenicity reduction of cow's milk proteins by various food processing techniques.

Circular RNAs: Novel target of diabetic retinopathy.

In diabetic patients, diabetic retinopathy (DR) is the leading cause of blindness and seriously affects the quality of life. However, current treatment methods of DR are not satisfactory. Advances have been made in understanding abnormal protein interactions and signaling pathways in DR pathology, but little is known about epigenetic regulation. Non-coding RNAs, such as circular RNAs (circRNAs), have been shown to be associated with DR. In this review, we summarized the function of circRNAs and indicated their roles in the pathogenesis of DR, which may provide new therapeutic targets for clinical treatment.

Retinal microglia polarization in diabetic retinopathy.

Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.

Potential Factors Affected Safety and Efficacy of Transcatheter Plug Closure for Pediatric Hemoptysis with Anomalous Bronchial Arteries.

OBJECTIVE: To evaluate the safety and efficacy of interventional care in pediatric hemoptysis for anomalous bronchial arteries (BAs) and to identify the potential factors resulting in hemoptysis recurrence. METHODS: 20 children complained of hemoptysis were diagnosed with anomalous BAs. All patients received transcatheter plug occlusion in Department of Cardiology, Children's Hospital of Chongqing Medical University. The safety and efficacy were evaluated according to clinical symptoms and images monitoring of enrolled subjects grouped as recurrence group and nonrecurrence group. The potential factors causing hemoptysis recurrence were reviewed and summarized. RESULTS: No deaths were recorded in a follow-up. Otherwise, hemoptysis recurrence was found in 8 subjects for 14 times, accounting for about 40%. Compared with nonrecurrence group, it indicated a statistical significance in hemoglobin levels (P=0.049), mycoplasma pneumonia particle assays (MP-PA) titers (P=0.030), and number of anomalous BAs (P=0.020). Meanwhile, 50% recurrent scenarios were associated with a respiratory infection by microbiological assessment before transcatheter plug occlusion. The repeat occlusion was applied for unclosed BAs leading to visual recurrent hemoptysis, the average interval time of which was 5.4 ± 3.6 mon. CONCLUSION: The data from this retrospective study have shown that transcatheter plug occlusion is a relatively safe procedure with a low mortality. The number of abnormal BAs has been identified as a highly significant predictor of recurrence, and the role of MP and other potential factors should be verified in a multicenter, larger sample size, and randomized controlled trial.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Damage to vascular endothelial cells by high insulin levels is associated with increased expression of ChemR23, and attenuated by PPAR-gamma agonist, rosiglitazone.

OBJECTIVE: This study investigated the effect of different insulin concentrations on the activity of vascular endothelial cells (VECs), and the role of PPARγ activator rosiglitazone (RGZ) on the expression of the chemerin receptor, ChemR23, in insulin-treated human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was determined in HUVECs treated with different insulin concentrations. Immunofluorescence staining was used to detect ChemR23 expression in insulin-treated HUVECs. Western blot assays were used to evaluate ChemR23 and PPARγ protein expression in insulin-treated HUVECs after pretreatment with PPARγ activator (RGZ) or inhibitor (GW9662). RESULTS: High insulin concentrations significantly inhibited HUVEC cell viability compared to low insulin concentrations, and this inhibition was attenuated by pretreatment with RGZ. High concentrations of insulin caused a significant upregulation of ChemR23 and a significant downregulation of PPARγ. These effects were attenuated by RGZ pretreatment, while PPARγ antagonist, GW9662 reversed this attenuation. CONCLUSION: ChemR23 upregulation may play a role in VEC damage caused by high concentrations of insulin. The protective effect of PPARγ activation in VECs may be mediated via ChemR23 downregulation.

Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D). METHODS: A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment. RESULTS: At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p < 0.001). Body weight and waist circumference were significantly decreased in the exenatide group but increased in the intensive insulin group (p < 0.001). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGGT) in the exenatide group were significantly lower than in the intensive insulin group (p < 0.001). The mean body weight change correlated with the levels of ALT, AST and γGGT change (ALT, r = 0.761; AST, r = 0.733; γGGT, r = 0.752; p < 0.001). Moreover, the reversal rate of fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p < 0.01). CONCLUSIONS: Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Decreased gastric body mucosa obestatin expression in abdominal obesity patients with normal body mass index.

The aim of the study was to investigate whether the expression of obestatin in gastric body mucosa in abdominal obesity patients with normal body mass index (BMI) is different compared with healthy controls. Twenty abdominal obesity patients with normal BMI and twenty healthy controls were included in the study. The number of obestatin-positive cells in gastric body mucosa was significantly lower in abdominal obesity patients with normal BMI than that in healthy subjects. There was a positive correlation between the numbers of obestatin-positive cells in the gastric body mucosa and plasma obestatin levels in abdominal obesity subjects and control group.

Effect of TRPV1 channel on proliferation and apoptosis of airway smooth muscle cells of rats.

Airway remodeling is an important pathological feature of asthma and the basis of severe asthma. Proliferation of airway smooth muscle cells (ASMCs) is a major contributor to airway remodeling. As an important Ca(2+) channel, transient receptor potential vanilloid 1 (TRPV1) plays the key role in the cell pathological and physiological processes. This study investigated the expression and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel on the ASMCs proliferation and apoptosis in order to provide the scientific basis to treat asthmatic airway remodeling in clinical practice. Immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of TRPV1 in rat ASMCs. Intracellular Ca(2+) was detected using the single cell confocal fluorescence microscopy measurement loaded with Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst 33258 staining were used to detect the proliferation and apoptosis of ASMCs in rats respectively. The data showed that: (1) TRPV1 channel was present in rat ASMCs. (2) TRPV1 channel agonist, capsaicin, increased the Ca(2+) influx in a concentration-dependent manner (EC50=284.3±58 nmol/L). TRPV1 channel antagonist, capsazepine, inhibited Ca(2+) influx in rat ASMCs. (3) Capsaicin significantly increased the percentage of S+G2M ASMCs and the absorbance of MTT assay. Capsazepine had the opposite effect. (4) Capsaicin significantly inhibited the apoptosis, whereas capsazepine had the opposite effect. These results suggest that TRPV1 is present and mediates Ca(2+) influx in rat ASMCs. TRPV1 activity stimulates proliferation of ASMCs in rats.

Changes of structure properties and potential allergenicity of ovalbumin under high hydrostatic pressures.

Egg proteins, notably ovalbumin (OVA), contribute to a prevalent form of food allergy, particularly in children. This study aims to investigate the impact of high hydrostatic pressure (HHP) treatment at varying levels (300, 400, 500, and 600 MPa) on the molecular structure and allergenicity of OVA. The structure of HHP-treated OVA was assessed through fluorescence spectroscopy, circular dichroism spectroscopy, and molecular dynamics (MD) simulation. HHP treatment (600 MPa) altered OVA structures, such as α-helix content decreased from 28.07 % to 19.47 %, and exogenous fluorescence intensity increased by 8.8 times compared to that of the native OVA. The free sulfhydryl groups and zeta potential value were also increased with HHP treatment (600 MPa). ELISA analysis and MD simulation unveiled a noteworthy reduction in the allergenicity of OVA when subjected to 600 MPa for 10 min. Overall, this study suggests that the conformational changes in HHP-treated OVA contribute to its altered allergenicity.

Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation.

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 µg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.