Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause Show more
Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause of their life expectancy being 15-20 years shorter than that of the general population. Identifying comorbidity patterns and uncovering differences in immune and metabolic function are crucial steps toward improving prevention and management strategies. A retrospective cross-sectional study was conducted using electronic medical records of inpatients discharged between 2015 and 2024 from a municipal psychiatric hospital in China. The study included patients diagnosed with Schizophrenia, Schizotypal, and Delusional Disorders (SSDs) (ICD-10: F20-F29). Comorbidity patterns were identified through latent class analysis (LCA) based on the 20 most common comorbid conditions among SSD patients. To investigate differences in peripheral blood metabolic and immune function, linear regression or generalized linear models were applied to 44 laboratory test indicators collected during the acute episode. The Benjamini-Hochberg method was used for p-value correction, and the false discovery rate (FDR) was calculated, with statistical significance set at FDR < 0.05. Among 3,697 inpatients with SSDs, four distinct comorbidity clusters were identified: SSDs only (Class 1), High-Risk Metabolic Multisystem Disorders (Class 2, n = 39), Low-Risk Metabolic Multisystem Disorders (Class 3, n = 573), and Sleep Disorders (Class 4, n = 205). Compared to Class 1, Class 2 exhibited significantly elevated levels of apolipoprotein A (ApoA; β = 90.62), apolipoprotein B (ApoB; β = 0.181), mean platelet volume (MPV; β = 0.994), red cell distribution width-coefficient of variation (RDW-CV; β = 1.182), antistreptolysin O (ASO; β = 276.80), and absolute lymphocyte count (ALC; β = 0.306), along with reduced apolipoprotein AI (ApoAI; β = -0.173) and hematocrit (HCT; β = -35.13). Class 3 showed moderate increases in low-density lipoprotein cholesterol (LDL-C; β = 0.113), MPV (β = 0.267), white blood cell count (WBC; β = 0.476), and absolute neutrophil count (ANC; β = 0.272), with decreased HCT (β = -9.81). Class 4 was characterized by elevated aggregate index of systemic inflammation (AISI; β = 81.07), neutrophil-to-lymphocyte ratio (NLR; β = 0.465), and systemic inflammation response index (SIRI; β = 0.346), indicating a heightened inflammatory state. The comorbidity patterns of patients with SCZ can be distinctly classified. During the acute episode, those with comorbid metabolic disorders exhibit a higher risk of cardiovascular diseases and immune system abnormalities, while patients with comorbid sleep disorders present a pronounced systemic inflammatory state and immune dysfunction. This study provides a basis for the chronic disease management and anti-inflammatory treatment, while also offering objective biomarker insights for transdiagnostic research. Show less
Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg Show more
Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg) fat deposits are associated with apoB levels in general US adults. 4585 participants were enrolled from the US National Health and Nutritional Surveys from 2011 to 2016. Overall and regional body fat were measured using dual-energy X-ray absorptiometry. The associations of total and regional fat with apoB levels were evaluated using linear regression models. Following adjustment for demographic, lifestyle, and clinical risk factors, whole-body fat percentage was positively associated with apoB levels. Additionally, percent trunk fat was positively associated (highest vs. lowest tertile beta = 17.73 for men and 14.89 for women, respectively), whereas percent leg fat was inversely associated (highest vs. lowest tertile beta = - 4.84 for men and - 6.55 for women, respectively) with apoB levels in both sexes. The association for trunk fat and leg fat remained significant after further adjustment for body mass index or waist circumference. Higher percent trunk fat combined with lower percent leg fat was associated with particularly higher apoB. In conclusion, among general US adults, both elevated trunk fat and reduced leg fat are associated with higher levels of apoB. Further research is required to elucidate the underlying pathophysiological mechanisms. Show less
Products encoded by approximately 30% of the mammalian genome exit the endoplasmic reticulum via the coat complex II (COPII) system en route to their functional destination. Among these cargoes, APOB- Show more
Products encoded by approximately 30% of the mammalian genome exit the endoplasmic reticulum via the coat complex II (COPII) system en route to their functional destination. Among these cargoes, APOB-containing lipoproteins stand out as abundant and bulky secretory particles with profound implications for human health and diseases. Recent insights into the specialized intracellular itinerary of lipoprotein metabolism and transport not only shed light on longstanding questions of lipid dynamics, but also highlight challenges faced by the COPII machinery in accommodating these complex, unconventional cargoes. Emerging evidence supports that tightly-regulated COPII condensation enables maximal capacity of cargo transport, providing a potential solution tailored for efficient lipoprotein delivery without affecting general protein secretion. This distinction suggests that targeting COPII condensation may provide new therapeutic strategies for lipid-associated diseases. Indeed, recent studies have identified manganese as a key modulator of this process, offering novel insights into its physiological relevance and potential translations. Show less
BackgroundAlthough abnormalities in circulating lipids and lipoproteins are associated with increased cancer risk, their specific impact on lung cancer progression and prognosis is still unclear. This Show more
BackgroundAlthough abnormalities in circulating lipids and lipoproteins are associated with increased cancer risk, their specific impact on lung cancer progression and prognosis is still unclear. This study retrospectively assessed the influence of preoperative lipid and lipoprotein levels on non-small cell lung cancer progression and prognosis, stratified by age.MethodsIn this retrospective study, we analyzed 849 patients to investigate the association between lipid markers and lung cancer progression, and examined postoperative prognosis in a subset of 222 patients. Data was analyzed using restricted cubic spline curves, Kaplan-Meier survival analysis, and Cox proportional hazards models.ResultsA significant nonlinear relationship was observed between total cholesterol (TC), high-density lipoprotein (HDL), ApoB, ApoAI, ApoE, and baseline tumor diameter (BSLD) (PTC = 0.025; PHDL < 0.001; PApoB = 0.037; PApoAI =0.001; PApoE < 0.001). In contrast, Lp(a) showed a significant linear relationship with BSLD (P = 0.002). The Cox regression analysis revealed that triglyceride (TG) (hazard ratio (HR) = 0.50, 95% confidence interval (CI): 0.28-0.92, P = 0.025) was significantly negatively associated with lung cancer mortality in patients under 58 years. For patients over 58 years, higher ApoB levels were linked to a reduced risk of lung cancer death (HR = 0.59, 95% CI: 0.36-0.97, P = 0.038).ConclusionThis study reveals a significant negative correlation between ApoAI and HDL levels with BSLD, while Lp(a) shows a positive correlation. In terms of long-term prognosis, high-serum ApoB are associated with a lower mortality risk in all lung cancer patients, and high-serum TG levels associated with reduced mortality risk in patients aged under 58 while high-serum TC levels associated with reduced mortality risk in patients over 58, with high Lp(a) levels indicating a greater risk of mortality in older patients. Show less
Maternal circulating lipid concentrations impact the risk of pregnancy complications and infant health outcomes. The associations between physical activity and circulating lipids during pregnancy rema Show more
Maternal circulating lipid concentrations impact the risk of pregnancy complications and infant health outcomes. The associations between physical activity and circulating lipids during pregnancy remain inadequately understood. A study was conducted from July 2024 to March 2025, involving the recruitment of 520 pregnant women in Wuhan, China. The Pregnancy Physical Activity Questionnaire (PPAQ) scores were evaluated in trimesters. Circulating lipid profiles, including total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (APOA1) and apolipoprotein B (APOB) concentrations, were assessed at each trimester. The daily energy expenditure of physical activity (EEPA) during the first, second, and third trimesters was recorded as 11.35, 9.07, and 9.48 metabolic equivalents-hour/day (METs-h/d). The EEPA in the first trimester was significantly greater than that in the second ( This study suggests that increased physical activity during pregnancy is associated with lower lipid levels. Moreover, maternal age appears to have a significant impact on physical activity and the metabolism of circulating lipids during pregnancy. Show less
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from u Show more
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less
This study aimed to elucidate the correlations among dyslipidemia, immune function, and clinical outcomes in patients with acute-on-chronic liver failure (ACLF), with particular emphasis on the clinic Show more
This study aimed to elucidate the correlations among dyslipidemia, immune function, and clinical outcomes in patients with acute-on-chronic liver failure (ACLF), with particular emphasis on the clinical significance of lipid metabolism and cellular immune parameters in hepatitis B virus-associated ACLF (HBV-ACLF). A retrospective analysis was conducted on 803 patients with HBV-ACLF admitted to the Shanghai Public Health Clinical Center from January 2014 to January 2024. Patients were stratified into deceased (n = 414) and survival (n = 389) groups based on clinical outcomes. Clinical baseline data, lipid metabolic indices, and cellular immune parameters were collected. The Spearman correlation coefficient was utilized to assess the correlation between lipid metabolic indices and cellular immune parameters, and a multivariate Cox proportional hazards model was applied to analyze risk factors for mortality. Compared to the survival group, lipid metabolism indices in the deceased group were significantly reduced (P < 0.05). Lipid metabolism indices, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), total cholesterol (TC), and triglycerides (TG), demonstrated significant negative correlations with the severity of liver failure (P < 0.05). Correlation analysis with lymphocyte subset counts revealed positive correlations between low-density lipoprotein, TG, TC, APOB, and CD3 + T cells, CD4 + T cells, CD8 + T cells, and CD45 + T cells (P < 0.05). APOA1 and HDL-C were positively correlated with B cells and NK cells (P < 0.05). TG and APOB showed significant negative correlations with the CD4/CD8 ratio (P < 0.05). Multivariate Cox analysis identified age, creatinine, total bilirubin, international normalized ratio (INR), hepatic encephalopathy, and hepatorenal syndrome as independent risk factors affecting the short-term prognosis of HBV-ACLF, while sodium, APOA1, and APOB were identified as independent protective factors for ACLF (HR = 0.984, 95% CI: 0.974-0.995, P < 0.001, HR = 0.267,95% CI: 0.120-0.596, P = 0.001, HR = 0.486, 95% CI: 0.282-0.838, P = 0.010). Patients with HBV-ACLF exhibit decreased levels of TC, TG, LDL-C, HDL-C, APOA1, and APOB. These alterations in serum lipid profiles are associated with immune dysfunction and disease progression in HBV-ACLF. Notably, APOA1 and APOB serve as protective factors against 90-day mortality in hospitalized ACLF patients. Further investigation is warranted to elucidate the relationship between lipid metabolism disturbances and peripheral immunity in ACLF. Show less
Previous studies have indicated that blood lipids can influence skeletal health. However, limited research exists on the impact of serum apolipoprotein B (ApoB) on bone mineral density (BMD); meanwhil Show more
Previous studies have indicated that blood lipids can influence skeletal health. However, limited research exists on the impact of serum apolipoprotein B (ApoB) on bone mineral density (BMD); meanwhile, it remains unclear to what extent cardiovascular disease plays in mediating this process. Therefore, we conducted a cross-sectional analysis involving 2930 participants from the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum ApoB and total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD). We employed a two-step, two-sample Mendelian randomization (MR) analysis using genetic instruments to investigate causality and assess the mediating effects of six cardiovascular diseases. Multivariable linear regression models demonstrated an inverse linear association between serum ApoB and TB-BMD (β = -0.26, 95% confidence interval (CI): -0.41 to -0.12, The results of this study support that lowering serum ApoB levels could enhance BMD while preventing the occurrence of heart failure might reduce the harm caused by the decrease in BMD due to elevated ApoB levels. Show less
Scatophagus argus is a highly valuable aquaculture fish. Its artificial breeding faces problems in the induction of high quality eggs, thus necessitating studies on the regulation of ovarian developme Show more
Scatophagus argus is a highly valuable aquaculture fish. Its artificial breeding faces problems in the induction of high quality eggs, thus necessitating studies on the regulation of ovarian development. As the centre of nutrient metabolism in fish, the liver provides the material basis for ovarian development. However, the molecular mechanism of the liver in ovarian development in S. argus is still unclear. In this study, a transcriptome analysis of adult S. argus livers at different stages of ovarian development (stages II, III and IV) was performed. 410, 1025 and 1867 differentially expressed genes (DEGs) were obtained between stages II and III, stages II and IV and stages III and IV, respectively. In GO and KEGG analyses, DEGs were mostly involved in vitellogenesis and egg envelope formation (e.g., erα, erβ1, vtga, vtgb, vtgc, zp3, zp4a and zp4b), lipid metabolism and energy metabolism (e.g., dagt1, dagt2, lpl, apob, hk1, acly, ogdh, pc, and fbp1), and hormone signaling (e.g., lepa and igfbp1). Additionally, genes that were significantly upregulated in the liver at stage IV of ovarian development, compared to stages II and III, were markedly enriched in steroid biosynthesis and metabolism pathways. These findings provide clues to understanding the mechanisms of liver action in teleost ovarian development. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a prevalent liver condition in children and teenagers with obesity. Unfortunately, there is no standardized treatment. To ex Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a prevalent liver condition in children and teenagers with obesity. Unfortunately, there is no standardized treatment. To examine the connection between apolipoprotein B (apoB), apolipoprotein A1 (apoA1), and the apoB/apoA1 ratio with the occurrence of MASLD in this population. A retrospective study was made on children and adolescents with obesity in a children's hospital between the period 2020 and 2022. Anthropometric data, ultrasound results, and blood biochemistry were analysed to assess the connection between apoB, apoA1, and the presence of MASLD. Of the 916 participants included, 313 were diagnosed with MASLD. The level of serum apoB reflected a substantial dose-response correlation with the odds of having MASLD. When apoB levels exceeded the 50th percentile, the risk increased significantly, and at the 95th percentile, the odds were 4.83 times higher than at the 50th percentile (95% CI: 2.02-11.56). The ratio of apoB/apoA1 at the 95th percentile was connected to a 2.41-fold higher prevalence compared to the 50th percentile (95% CI: 1.33-4.37). No significant correlation was found between the levels of apoA1 and MASLD prevalence. Elevated levels of apoB and the apoB/apoA1 ratio have been strongly connected to increased MASLD prevalence in children and adolescents with obesity; hence, signifying their potential usefulness as biomarkers for early detection and intervention. Show less
Currently, understanding of the nonlinear relationship between age and hepatocellular carcinoma (HCC) prognosis is insufficient. Thus, this study aimed to analyze the relationship between age at HCC d Show more
Currently, understanding of the nonlinear relationship between age and hepatocellular carcinoma (HCC) prognosis is insufficient. Thus, this study aimed to analyze the relationship between age at HCC diagnosis and overall survival (OS) and identify possible influencing mechanisms. Clinical data from the TCGA public database were analyzed. Restricted cubic spline and segmented logistic regression were employed to explore the nonlinear relationship between age at diagnosis and mortality risk following hepatectomy. Furthermore, bioinformatics methods were employed to understand the possible mechanisms of this nonlinear relationship at the genetic level. The results indicated a nonlinear relationship between age at diagnosis and OS, with the age of 60 years identified as a critical point. Segmented regression showed that age ≥60 years is an unfavorable prognostic factor. The "DNA mismatch repair" pathway was considerably enriched in patients aged <60 years. However, the gene mutation rate of "APOB," "MUC16," "ALB," and "PCLO" and the median tumor mutation burden were relatively more evident in patients aged ≥60 years. MGEA12 was more highly expressed in tumor tissues than in normal ones, particularly in patients aged ≥60 years. The survival rate of the high-expression group was lower than that of the low-expression group. At the mRNA level, the MGEA12 expression in Huh-7 and SUN449 was higher than that in the HSC-LX2 cell line. A nonlinear relationship was found between age at HCC diagnosis and OS, with the age of 60 years being the critical point. MGEA12 may affect the prognosis of elderly people. Show less
We have designed the first antigen-less pro-vaccine, named 8206, for treating autoimmune diseases. Composed of dexamethasone, rapamycin, and R848 at a mass ratio of 8:20:6, 8206 is a complete toleroge Show more
We have designed the first antigen-less pro-vaccine, named 8206, for treating autoimmune diseases. Composed of dexamethasone, rapamycin, and R848 at a mass ratio of 8:20:6, 8206 is a complete tolerogenic adjuvant that acts systemically to form an active vaccine in situ with endogenous pathogenic autoantigens. This active vaccine suppresses autoimmunity by expanding antigen-specific Treg cells in affected tissues. In a mouse model of atherosclerosis, 8206 successfully targeted all three analyzed pathogenic autoantigens (ApoB, HSP60, and HMGB1) and inhibited disease progression. These findings suggest that 8206 can potentially serve as a universal treatment vaccine for autoimmune diseases by eliminating the need for exogenous immunogens, with implications for broad applications in immunotherapy. Show less
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contr Show more
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contributing to stroke remains poorly understood. This study aims to investigate the association between the apoB/apoA1 ratio and intracranial or extracranial atherosclerosis. We enrolled 408 patients with acute ischemic stroke who had never been treated with statins or fibrates. Based on the images from computed tomography angiography (CTA), the patients were categorized into four groups: intracranial atherosclerosis stenosis (ICAS, n = 136), extracranial carotid atherosclerosis stenosis (ECAS, n = 45), combined intracranial and extracranial atherosclerosis stenosis (COAS, n = 73), and non-cerebral atherosclerosis stenosis (NCAS, n = 154). Demographic characteristics, clinical factors, and serum lipid levels were collected and then compared across groups. The apoB/apoA1 ratio was significantly higher in patients with ICAS, ECAS and COAS compared to those in the NCAS group. Multivariable logistic regression analysis demonstrated that the ApoB/ApoA1 ratio was independently associated with ICAS, but not with ECAS. ROC curve analysis showed that the ApoB/ApoA1 ratio had a good diagnostic ability for ICAS, with an area under the curve (AUC) of 0.764, an optimal cut-off value of 0.8122, a sensitivity of 81.3%, and a specificity of 59.8%. An higher apoB/apoA1 ratio is associated with ICAS in ischemic stroke patients. Show less
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelia Show more
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelian randomization study. The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 genetic variants available for analysis. Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes. Thirteen lipid biomarkers, VA, and CRT. A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD. This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Show less
The per-particle pathogenicity of very-low-density lipoprotein (VLDL) and lipoprotein(a) [Lp(a)] with risk of valvular heart diseases (VHD) other than aortic stenosis compared with low-density lipopro Show more
The per-particle pathogenicity of very-low-density lipoprotein (VLDL) and lipoprotein(a) [Lp(a)] with risk of valvular heart diseases (VHD) other than aortic stenosis compared with low-density lipoprotein (LDL) remains unclear. Single-nucleotide polymorphism specific clusters associated with LDL cholesterol (LDL-C), VLDL cholesterol (VLDL-C) and Lp(a) were identified. The relationships of genetically predicted variation in apolipoprotein B (apoB) in these lipoproteins with risk of VHD and its major types (aortic stenosis, aortic regurgitation, and mitral regurgitation) were evaluated to determine the comparative pathogenicity by Mendelian randomization (MR) analyses. The VHD odds ratio (OR) per 1 g/L higher apoB was 1.09 [95 % confidence interval (CI) 1.04-1.15] in LDL vs. 1.45 (95 % CI 1.25-1.69) in VLDL vs. 2.71 (95 % CI 1.92-3.82) in Lp(a) based on the cluster-based MR analyses. The polygenic scores for each lipoprotein weighted by apoB similarly showed a greater OR of VHD per 1 g/L apoB in VLDL [1.20 (95 % CI 1.06-1.37)] and in Lp(a) [2.54, (95 % CI 1.95-3.32)] compared with that in LDL [1.05 (95 % CI 1.01-1.08)]. Multivariable MR analyses further revealed the strong effects of VLDL-C and Lp(a) on VHD risk independent of LDL-C. In addition, significant associations between Lp(a) and all three major types of VHD were observed, while LDL and VLDL had no impact on aortic and mitral regurgitation. VLDL and Lp(a) appear to have significantly greater per-particle pathogenicity in VHD compared to LDL. The distinct impacts of lipoproteins on different VHD subtypes suggest the inadequacy of just focusing on LDL-lowering treatment for valve disorders. Show less
Aromatase, encoded by Cyp19a1, is the rate limiting enzyme in biosynthesis of estrogens, and excessive aromatase can reduce the semen quality in roosters. Seminal plasma extracellular vesicles (SPEV) Show more
Aromatase, encoded by Cyp19a1, is the rate limiting enzyme in biosynthesis of estrogens, and excessive aromatase can reduce the semen quality in roosters. Seminal plasma extracellular vesicles (SPEV) are nanoscale vesicles that carry and transmit signaling molecules, thereby affecting semen quality. Currently it is still unclear whether SPEV are involved in the process of that aromatase affects the quality semen in chicken. To clarify this issue, lentivirus carrying Cyp19a1 (LV-CYP19A1) for over-expression of aromatase was constructed and injected to testis of 35-week-old roosters. Semen quality and seminal plasma hormone were measured, and SPEV were also extracted and proteome sequencing was performed after treatment of LV-CYP19A1. The results indicated that semen volume, fertility, sperm motility, testosterone (T) levels were significantly decreased, and estradiol (E Our results reveal that aromatase can down-regulate the protein expression related to regulation of ATP synthesis and metabolism, and sperm motility in SPEV, thereby reducing semen quality in roosters. Show less
Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we id Show more
Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we identified RNA binding motif protein 39 (Rbm39) as a key modulator of hepatic lipid homeostasis during MASLD progression. To establish in vivo MASLD model, mice were fed either a high-fat diet (HFD) or a Gubra-Amylin NASH (GAN) diet. We employed adeno-associated virus to manipulate Rbm39 expression levels to assess its role in MASLD. Transcriptome analysis was conducted to pinpoint the genes targeted by Rbm39. Western blot, RT-PCR, dual-luciferase reporter gene assays, and alternative splicing analysis were utilized to delve into the molecular mechanisms. Our results showed that Rbm39 expression was notably decreased in the livers of MASLD mice. Knockdown of hepatic Rbm39 aggravated HFD-induced hepatic steatosis and GAN diet-induced MASH, along with a notable decrease in serum lipid levels. Conversely, overexpression of Rbm39 attenuated MASLD development and progression. RNA sequencing data analysis indicated that Rbm39 regulated the expression of apolipoprotein B (Apob) and fatty acid-binding protein 4 (Fabp4), both of which are crucial for lipid transport. Mechanistically, Rbm39 enhanced the transcription of Apob by upregulating hepatocyte nuclear factor 4α (Hnf4α), while it suppressed Fabp4 transcription by regulating alternative splicing of hypoxia inducible factor-1α (Hif-1α). These findings highlight the pivotal role of Rbm39 in maintaining hepatic lipid homeostasis and suggest its potential as a therapeutic target for MASLD. Show less
The objective was to assess the clinical efficacy of long non-coding RNA (lncRNA) alpha-2-macroglobulin-antisense 1 (A2M-AS1) in acute myocardial infarction (AMI). One hundred patients with AMI and ei Show more
The objective was to assess the clinical efficacy of long non-coding RNA (lncRNA) alpha-2-macroglobulin-antisense 1 (A2M-AS1) in acute myocardial infarction (AMI). One hundred patients with AMI and eighty patients with chest pain were recruited in the case-control study. A2M-AS1 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was utilized for evaluating the diagnostic value. Pearson's correlation analysis was used to analyze the correlation between A2M-AS1 and conventional AMI biomarkers. AMI-associated risk indicators were identified using logistic regression analysis. A significant reduction of serum A2M-AS1 was measured in AMI patients relative to chest pain patients. A2M-AS1 had an area under the curve (AUC) of 0.927 to distinguish AMI patients from those with chest pain. Pearson's correlation analysis showed that A2M-AS1 was adversely correlated with white blood cell (WBC) (r=-0.6682, P < 0.001), low density lipoprotein cholesterol (LDL-C) (r=-0.5795, P < 0.001), creatine kinase MB (CK-MB) (r=-0.6022, P < 0.001) and cTnl (r=-0.5473; P < 0.001), while positively correlated with high density lipoprotein cholesterol (HDL-C) (r = 0.6445, P < 0.001). Relative to non-Major Adverse Cardiovascular Events (non-MACE) group, serum A2M-AS1 was obviously declined in the MACE group of AMI patients with high capacity to distinguish the MACE group from the non-MACE patients (AUC = 0.802). Additionally, A2M-AS1 (P = 0.013; OR = 0.268; 95%CI = 0.095-0.760) was a risk indicator for predicting MACE with AMI patients, as well as age (P = 0.014; OR = 3.478; 95%CI = 1.285-9.414). A reduction in A2M-AS1 expression was observed in AMI patients, suggesting its potential as an underlying indicator for AMI diagnosis. Show less
The gut microbiota plays a crucial role in human health, but its impact on lipid metabolism remains unclear. Understanding the causal relationship between gut bacteria and lipid profiles is essential Show more
The gut microbiota plays a crucial role in human health, but its impact on lipid metabolism remains unclear. Understanding the causal relationship between gut bacteria and lipid profiles is essential for developing strategies to prevent and treat dyslipidemia and cardiovascular diseases. This study aimed to assess this relationship using two-sample Mendelian randomization (MR). Data for both exposure and outcomes were obtained from the IEU-GWAS database, with lipid profile data sourced from a publication. Genome-wide significant single nucleotide polymorphisms (SNPs), which were independent of outcome factors but correlated with exposure variables, were identified as instrumental variables. Several MR methods, including weighted analysis, maximum likelihood, inverse variance weighting (IVW), MR-Egger, and weighted median, were applied. Colocalization analysis further validated the findings. The analysis revealed microbial groups with causal relationships to ApoA1, ApoB, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglycerides. Reverse MR and colocalization analysis provided additional confirmation of these results. This study offers new evidence of the causal link between gut microbiota and lipid profiles, providing insights for improving lipid profiles and reducing cardiovascular disease risk. Show less
In mammals, tissues other than liver and intestine are known to possess functional MTTP (microsomal triglyceride transfer protein) and apoB (apolipoprotein B) capable of VLDL (very low-density lipopro Show more
In mammals, tissues other than liver and intestine are known to possess functional MTTP (microsomal triglyceride transfer protein) and apoB (apolipoprotein B) capable of VLDL (very low-density lipoprotein) assembly. Birds are oviparous and possess unique capabilities in lipid biology to accommodate yolk formation through massive deposition of hepatically assembled yolk-targeted VLDLy into ovarian follicles. Following identifications of MTTP and ApoB expression within chicken ovarian stroma, granulosa, theca, and epithelial cells of various classes of follicles, we sought to define the functionality of ovarian MTTP and ApoB in VLDL assembly. In situ hybridization analysis found that ApoB transcripts are most abundant in thecal layers, whereas immunohistochemistry showed that MTTP predominates in the granulosa layers. MTTP lipid transfer activity was greater in small yellow follicles than in hierarchical follicles. Metabolic labeling, electron microscopy, and Western blot studies confirmed the functionality of ovarian apoB and MTTP as newly assembled VLDL around 50-200 nm in diameter and lacking ApoVLDL-II dissimilar to VLDLy, were secreted from cultured follicular cells. Lomitapide and the ApoB-antisense oligonucleotide Mipomersen dose-dependently decreased MTTP activity and VLDL-apoB secretion from cultured follicular cells, while oleate addition or acute heat stress enhanced VLDL-apoB secretion. Ultrastructural images showed VLDL assembly and trafficking toward the secretion route. The findings support the notion that VLDL assembly and secretion within avian ovarian tissues functions as a protective mechanism against fuel and physical stressors to secure follicle development and/or nutritional quality control of yolk for embryo development. Show less
Genome-wide association studies (GWAS) have identified common variants associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, rare coding variant studies have been Show more
Genome-wide association studies (GWAS) have identified common variants associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, rare coding variant studies have been limited by phenotyping challenges and small sample sizes. We test associations of rare and ultra-rare coding variants with proton density fat fraction (PDFF) and MASLD case-control status in 736,010 participants of diverse ancestries from the UK Biobank, All of Us, and BioMe and performed a trans-ancestral meta-analysis. We then developed models to accurately predict PDFF and MASLD status in the UK Biobank and tested associations with these predicted phenotypes to increase statistical power. The trans-ancestral meta-analysis with PDFF and MASLD case-control status identifies two single variants and two gene-level associations in APOB, CDH5, MYCBP2, and XAB2. Association testing with predicted phenotypes, which replicates more known genetic variants from GWAS than true phenotypes, identifies 16 single variants and 11 gene-level associations implicating 23 additional genes. Two variants were polymorphic only among African ancestry participants and several associations showed significant heterogeneity in ancestry and sex-stratified analyses. In total, we identified 27 genes, of which 3 are monogenic causes of steatosis (APOB, G6PC1, PPARG), 4 were previously associated with MASLD (APOB, APOC3, INSR, PPARG), and 23 had supporting clinical, experimental, and/or genetic evidence. Our results suggest that trans-ancestral association analyses can identify ancestry-specific rare and ultra-rare coding variants in MASLD pathogenesis. Furthermore, we demonstrate the utility of machine learning in genetic investigations of difficult-to-phenotype diseases in trans-ancestral biobanks. Show less
Aim Aortic aneurysm is characterized by localized expansion and damage to the vessel wall. While apolipoprotein B (ApoB) has been linked to atherosclerosis, its causal relationship with aortic aneu Show more
Aim Aortic aneurysm is characterized by localized expansion and damage to the vessel wall. While apolipoprotein B (ApoB) has been linked to atherosclerosis, its causal relationship with aortic aneurysm remains unclear. This study used a Mendelian randomization (MR) approach to explore the causal relationships between ApoB, aortic aneurysm, and potential mediators.Material and methods Single nucleotide polymorphism (SNP) data related to ApoB, apolipoprotein A1 (ApoA1), triglycerides, frailty index, and aortic aneurysm were obtained from large-scale genome-wide association studies. MR analysis was conducted to evaluate causal relationships, using inverse variance weighting (IVW) as the primary statistical method. Additionally, we assessed whether the frailty index mediates the relationship between ApoB and aortic aneurysm.Results Univariate MR analysis revealed that ApoB is significantly associated with aortic aneurysm (IVW odds ratio (OR) = 1.443, 95 % confidence interval (CI) = 1.273-1.637, p < 0.001). Multivariable MR (MVMR) analysis, adjusted for ApoA1 and triglycerides, confirmed these results. In mediation analysis, the frailty index was found to partially mediate the effect of ApoB on aortic aneurysm (mediation contribution: 20.1 %-23.1 %). The ORs for ApoB and the frailty index with respect to aortic aneurysm were 1.325 (95 % CI = 1.168-1.505) and 4.188 (95 % CI = 1.859-9.435), respectively.Conclusion ApoB has a causal relationship with aortic aneurysm, with the frailty index acting as a partial mediator in this pathway. Show less
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregn Show more
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less
Adiponectin is an anti-diabetic and anti-atherogenic protein secreted primarily from adipose tissue. Adiponectin and modified LDL (mLDL) form a complex to modulate their biological activity. To elucid Show more
Adiponectin is an anti-diabetic and anti-atherogenic protein secreted primarily from adipose tissue. Adiponectin and modified LDL (mLDL) form a complex to modulate their biological activity. To elucidate the significance of the complex formation, we analyzed its effects on vascular tissue and developed and verified novel quantifying methods for adiponectin. To study the significance of the mLDL-adiponectin complex (MAC) formation, we used the wire-myography method on rat mesenteric artery. We developed a method to measure MAC by using LOX-1 as the capture protein and anti-adiponectin antibody for detection. We compared serum MAC levels between hemodialysis patients and control subjects. Administering mLDL alone to rat mesenteric artery impaired endothelium-dependent vasorelaxation, whereas simultaneously administering adiponectin with mLDL protected rat mesenteric artery from the mLDL-induced impairment of vasorelaxation. This finding indicates MAC formation prevents endothelium from mLDL-induced dysfunction in tissue. Using our novel ELISA for MAC, we found that MAC was increasingly detectable depending on the doses of mLDL and adiponectin in vitro. In serum, hemodialysis patients showed a significantly higher ratio of MAC-high patients (higher than the median level of MAC) than did healthy controls. Furthermore, the MAC-high hemodialysis group had lower mLDL activity measured as LOX-1 ligand containing apoB. Using our ELISA, we detected MAC in human serum that protected blood vessels from the deleterious effects of oxidized LDL. Show less
Growing evidence suggests that lipid metabolism may play a crucial role in mood disorder pathophysiology, and the correlation between blood lipids and mood disorder remains further clarified. This pro Show more
Growing evidence suggests that lipid metabolism may play a crucial role in mood disorder pathophysiology, and the correlation between blood lipids and mood disorder remains further clarified. This prospective, population-based cohort study utilized data from the UK Biobank. The study included 268,098 and 292,121 participants who had never been diagnosed with depression or bipolar disorder and who had complete data at both the baseline and follow-up points. A principal component analysis (PCA) was conducted on seven blood lipids, and the first three principal components (PCs) were derived. Cox regression analysis was employed to examine the correlation between the risk of mood disorders and the PCs. Multiplicative interaction and sensitivity analyses were also conducted. The relationship between blood lipids and neurological biomarkers was explored using Spearman's analysis. PC1, primarily reflecting levels of Apolipoprotein B (ApoB), cholesterol, and low-density lipoprotein cholesterol (LDL-C), showed a protective effect against depression, with HRs of 0.98 (95 % CI: 0.96,1.00) in the fully adjusted Cox regression model. In contrast, PC2, characterized by opposite loadings for triglycerides and high-density lipoprotein cholesterol (HDLC), was positively associated with the risk of depression and bipolar disorder.(HR = 1.03,95 % CI: 1.01,1.06; HR = 1.11, 95 % CI: 1.01,1.23). Increased PC2 level was related to a significant increase in bipolar disorder risk among participants with high genetic risk (genetic risk score > 90 %, HR = 1.22, 95 % CI: 1.02,1.46). Complicated correlations between blood lipids and serum neuroproteins were detected. These findings suggest complex associations between blood lipid profiles and the risk of depression and bipolar disorder. Show less
Rotator cuff tear is the most common tendon injury. Currently, arthroscopic rotator cuff repair (ARCR) is the primary method for diagnosing and treating rotator cuff tear. One of the major complicatio Show more
Rotator cuff tear is the most common tendon injury. Currently, arthroscopic rotator cuff repair (ARCR) is the primary method for diagnosing and treating rotator cuff tear. One of the major complications following ARCR is retear. This study aims to evaluate the correlation between systemic lipid metabolism and retear occurrence after ARCR through a retrospective analysis of postoperative patients. This retrospective study reviewed consecutive patients of a single surgeon who underwent ARCR from January 2021 to January 2022. Eligibility for inclusion required complete sequential follow-up data, encompassing preoperative laboratory tests and a series of postoperative magnetic resonance imaging (MRI) evaluations at 1, 2, 3, and 6 months. Exclusion criteria included patients with incomplete laboratory tests, a history of tumors, prior shoulder surgeries, isolated subscapularis tendon tears, the rotator cuff related muscles are not clearly or completely displayed in MRI, absence of follow-up MRI, or those under treatment with lipid-lowering medications. Logistic regression analysis was employed to identify preoperative factors associated with retear, with statistical significance adjudged at P < .05. From the initial cohort of 400 patients who underwent ARCR during the study period, 202 met both inclusion and exclusion criteria. These patients were subsequently divided into a training group (n = 122) and a test group (n = 80), maintaining a ratio of 6:4. Statistical analysis revealed significant risk factors for post-ARCR retear including high body mass index (>27.1; odds ratio (OR): 5.994, 95% confidential interval (CI): 1.762-13.980; P = .042), subscapularis muscle fatty infiltration of Grades 3 and 4 (OR: 8.509, 95%CI: 3.811-17.702; P = .009), serum apolipoprotein B (ApoB) levels exceeding 1.4 g/L (OR: 9.658, 95%CI: 3.520-21.753; P = .028), and an ApoB/A1 ratio greater than 1.8 (OR: 5.098, 95%CI: 1.787-10.496; P = .016). Conversely, the serum high-density lipoprotein level above 1.2 mmol/L (OR: -3.342, 95%CI: -7.466 to 0.659; P = .039) served as a protective factor. The model incorporating these 5 factors predicted retear with a sensitivity of 78.3% and specificity of 98.0% (area under the curve = 0.924, accuracy = 90.3%). Moreover, a new model comprising 3 lipid metabolism-related factors including high-density lipoprotein, ApoB and the ApoB/A1 ratio showed a sensitivity of 80.5% and specificity of 83.2% (area under the curve = 0.866, accuracy = 85.8%) for predicting retear after ARCR. A predictive model utilizing key systemic lipid metabolism markers including HDL, ApoB, and the ApoB/A1 ratio, demonstrates effective forecasting of retear incidence following ARCR. Show less
This study aimed to analyse the relationship of the blood lipid profile and interleukin-6 (IL-6) with osteoporosis and osteopenia and to explore the predictive value of the combined application of the Show more
This study aimed to analyse the relationship of the blood lipid profile and interleukin-6 (IL-6) with osteoporosis and osteopenia and to explore the predictive value of the combined application of these biomarkers in osteoporosis and osteopenia. Data from 276 patients treated in the orthopaedics department were retrospectively analysed. Their general information was collected, and the relationships among the blood lipid profile, IL-6 with bone turnover markers, and bone mineral density (BMD) were analysed. Patients were categorized based on their T scores for intergroup comparisons. Finally, the diagnostic efficiency of lipid metabolism markers and IL-6 for osteoporosis and osteopenia was assessed using receiver operating characteristic (ROC) curves. (1) In both males and females, a negative relationship was observed between BMD and several biomarkers, including total cholesterol (TC), apolipoprotein B (ApoB), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFAs), and IL-6. Additionally, apolipoprotein A1 (ApoA1) was negatively correlated with BMD only in females, and the ApoA1/ApoB ratio was positively correlated with BMD only in males. (2) FFAs and IL-6 were positively correlated with β-CrossLaps peptide in males. However, for females, TC, ApoB, LDL-C, and IL-6 were negatively correlated with 25-hydroxyvitamin D. FFAs, IL-6, and age were negatively correlated with osteocalcin in males and females. (3) According to the T scores for the lumbar spine, the TC, ApoA1, ApoB, HDL-C, LDL-C, FFA, and IL-6 levels in the osteoporosis group and the TC, ApoB, LDL-C, and FFA levels in the osteopenia group were significantly greater than those in the normal bone mass group. Additionally, the osteoporosis group presented substantially higher levels of ApoA1, FFAs, and IL-6 than the osteopenia group. (4) IL-6 was positively correlated with FFAs, while a negative correlation was observed with TC, ApoA1, ApoB, HDL-C, and LDL-C. (5) The ROC curve revealed that the areas under the curve (AUCs) of TC, FFAs, IL-6, ApoA1, and the ApoA1/ApoB ratio for predicting osteoporosis or osteopenia were 0.634, 0.713, 0.670, 0.628, and 0.516, respectively, whereas the AUC of the combination of TC, FFAs, IL-6, and ApoA1 was 0.846, and the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.842. In the sex stratification analysis, in males, the AUCs of TC, FFAs, IL-6, and the ApoA1/ApoB ratio for the prediction of osteoporosis or osteopenia were 0.596, 0.688, 0.739, and 0.539, respectively. In contrast, the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.838. In females, the AUCs of TC, FFAs, IL-6, ApoA1, and the ApoA1/ApoB ratio for predicting osteoporosis or osteopenia were 0.620, 0.728, 0.653, 0.611, and 0.502, respectively, whereas the AUC of the combination of TC, FFAs, IL-6, and ApoA1 was 0.841, and the AUC of the combination of TC, FFAs, IL-6, and the ApoA1/ApoB ratio was 0.828. The levels of TC, FFAs, IL-6, ApoA1, and ApoB could contribute to changes in bone metabolism, moreover, FFAs could induce an increase in IL-6 further aggravating bone mass loss and leading to osteoporosis. Based on the comparison of the AUC results, the combination of TC, FFAs, and IL-6 with ApoA1 or the ApoA1/ApoB ratio can better predict osteoporosis or osteopenia in patients, and the diagnostic efficiency is significantly better than that of any individual indicator. The regulation of blood lipid levels should become a new target for clinicians to treat osteoporosis and osteopenia. Show less
Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of Show more
Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Whether SFA and UFA are differentially transported in liver remains elusive. Here, we find the secretion of UFA but not SFA esters is retarded in a male mouse hepatic endoplasmic reticulum (ER) stress model. Among 13 members of protein disulfide isomerase (PDI) family, only PDIA1 (PDI) deficiency leads to hepatosteatosis and hypolipidemia. In PDI-deficient male mouse liver, there is a severe accumulation but secretory blockade of UFA esters, whereas the accumulation and secretion of SFA esters remain normal. PDI catalyzes the oxidative folding of microsomal triglyceride transfer protein (MTP). In addition, PDI deficiency in hepatocytes abolishes Apolipoprotein B-100 (ApoB-100) very low-density lipoprotein (VLDL) secretion while maintaining partial ApoB-48 VLDL secretion. In summary, we find that the secretion of UFA esters is PDI-MTP indispensable, while SFA esters could be transferred out of liver via ApoB-48 VLDL through a PDI-MTP-independent pathway. Show less
Per- and polyfluoroalkyl substances (PFAS) pose potential health risks to lipid metabolism, but the effects of emerging PFAS alternatives, particularly in children, remain unclear. This cross-sectiona Show more
Per- and polyfluoroalkyl substances (PFAS) pose potential health risks to lipid metabolism, but the effects of emerging PFAS alternatives, particularly in children, remain unclear. This cross-sectional study investigated the association between emerging PFAS exposure and lipid levels in 294 Chinese children aged 7-10 years, analyzing blood samples for 14 PFAS and lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). Exposure to 6:2 Cl-PFESA, PFO4DA, and PFO5DoDA was associated with higher TC, TG, and LDL levels, with PFO4DA increasing the TC by 1.7% and PFO5DoDA increasing the TG by 10.7%. Weighted quantile sum (WQS) regression showed mixed PFAS exposure positively associated with TG (0.08, 95% CI: 0.007, 0.153). PFO4DA had the highest weight for TC (0.468), TG (0.327), LDL (0.57), ApoA1 (0.243), and ApoB (0.466), while PFMOAA had the highest weight for HDL (0.332). Bayesian Kernel Machine Regression (BKMR) analysis confirmed positive associations between the PFAS mixture and TC, TG, LDL, and ApoA1. Mediation analysis revealed that mtDNAcn significantly mediated PFAS exposure's effect on TG levels, explaining 27.2-74.2% of the total effect. These findings highlight the need for regulatory action to address the emerging PFAS risks. Show less