BACKGROUND:Thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are key biomarkers reflecting coagulation/fibrinolysis activation and endothelial injury. Population-specific reference intervals (RIs) are essential for accurate diagnosis, but Chinese-specific RIs remain limited. This study aimed to establish reliable RIs for these four markers in a Chinese population using indirect methods applied to clinical big data. METHODS:Anonymized clinical data for TAT, PIC, TM, and t-PAIC from 2020 to 2024 at Beijing Anzhen Hospital, Capital Medical University, were collected. After data reduction, deduplication, and outlier removal, RIs were calculated for the overall population and stratified by sex and age using indirect methods (Hoffmann and Bhattacharya). Reliability was verified by comparing the derived RIs with manufacturer-provided ranges using reference change value (RCV) criteria. RESULTS:Overall RIs determined by the Hoffmann method for TAT, PIC, TM, and t-PAIC were 0.64-3.57 ng/mL, 0.25-1.08 μg/mL, 5.64-13.42 TU/mL, and 3.22-15.88 ng/mL, respectively. Those determined by the Bhattacharya method were 0.58-2.84 ng/mL, 0.25-1.11 μg/mL, 5.60-14.53 TU/mL, and 3.46-15.44 ng/mL, respectively. TAT and PIC levels were higher in females, whereas TM and t-PAIC were higher in males. All four markers increased with age. Relative differences between method-derived RIs and manufacturer ranges were within RCV limits. CONCLUSION:Both Hoffmann and Bhattacharya's indirect methods are reliable for establishing RIs for TAT, PIC, TM, and t-PAIC. The study provides population-specific RIs for a Chinese cohort, supporting accurate early detection and risk assessment of thrombotic diseases.

Postoperative delirium (POD) and emergence delirium (ED) commonly occur in elderly and pediatric patients undergoing anesthesia. Electroencephalography (EEG)-based monitoring technologies, including Bispectral Index (BIS), SedLine EEG monitoring, and other EEG techniques, have been proposed as potential strategies for reducing delirium risk, but current evidence remains controversial. Therefore, this systematic review and meta-analysis aimed to evaluate the impact of EEG-guided anesthesia on delirium incidence in patients of various age groups. PubMed, Embase, Web of Science, and the Cochrane Library were searched upto August 2025 for studies investigating EEG-guided anesthesia depth and delirium outcomes. The primary outcomes included incidence of POD and Pediatric Anesthesia Emergence Delirium (PAED) scores. Meta-analysis and subgroup analyses based on EEG monitoring techniques were conducted using Stata software. Publication bias was assessed with Begg’s and Egger’s tests. Twenty studies involving 7344 adult patients and 463 pediatric patients were included. Pooled analyses indicated that deep anesthesia significantly increased POD risk in elderly patients (P = 0.008). For adult patients, EEG-guided anesthesia was associated with a significant reduction in POD compared with usual care (P = 0.001). In elderly patients, EEG-guided anesthesia was associated with a non-significant trend toward lower postoperative delirium (P = 0.123). For pediatric patients, EEG monitoring did not significantly affect PAED scores overall (P = 0.143); however, subgroup analysis revealed that non-BIS modality may have reduced PAED scores (P < 0.001). The effectiveness of EEG-guided anesthesia in reducing delirium risk varies across age groups. EEG monitoring effectively decreases POD incidence in adults. Among elderly patients, EEG-guided anesthesia did not significantly reduce the risk of POD, whereas non-BIS modality may confer greater benefit for pediatric emergence delirium. These findings are hypothesis-generating; future studies should define age-tailored EEG monitoring strategies and clarify indications across patient groups.

BACKGROUND:This research primarily concentrated on investigating the impact of plasma exchange, especially the modified double filtration plasmapheresis (M-DFPP), in cases of septic shock (SS). Different from traditional plasma exchange which simply removes some macromolecular pathogenic solutes and protein-binding solutes, M-DFPP, based on DFPP, switches the return and discard ports to remove inflammatory mediators more accurately with less plasma used. METHODS:A 67-year-old male patient suffered a right femoral neck fracture in a road accident and underwent right hemiarthroplasty. Twelve days post-surgery, he developed persistent lower abdominal pain and fever. Emergency surgical exploration revealed a retroperitoneal abscess caused by sigmoid colon perforation. Subsequently, the patient was admitted to the ICU for SS treatment. The treatment plan included fluid resuscitation, vasoactive medications, antibiotics, ventilator support, and M-DFPP. Each M-DFPP session exchanged 400 mL of plasma, which accounted for approximately 15% of the patient's total plasma volume. The patient underwent two M-DFPP sessions on the first and second days of admission, with a cumulative treatment time of 4 hours. The long treatment time was due to the need to ensure the stability of the patient's condition during the procedure. Slow-flow operation was adopted to minimize the risk of adverse reactions, such as hypotensive episodes or electrolyte imbalances. RESULTS:After two rounds of plasma exchange, there was a significant decline in plasma inflammatory factors related to SS, such as a decrease in TNF-α from 76.5 to 25.4 pg/mL, IL-6 from 1,000 to 178 pg/mL, and IL-8 from 7,500 to 512 pg/mL. The patient's hemodynamic condition improved remarkably, with heart rate decreasing from 128 to 95 beats per minute, blood pressure rising from 80/40 to 127/64 mmHg, and urine output increasing from 20 to 125 mL/hour. The dosage of vasoactive medications was gradually reduced until they were no longer required. However, due to ineffective management of the retroperitoneal infection, the patient's sepsis deteriorated on the 38th day of ICU admission, and the patient passed away on the 41st day. CONCLUSIONS:Compared with traditional continuous renal replacement therapies, M-DFPP is more efficient in eliminating inflammatory substances, simplifying the management of SS. It is a safe, user-friendly, and easily implementable method. Early application of M-DFPP can potentially reduce the damage of the body's inflammatory response to organs and lower the risk of organ failure. Future research is expected to further explore its effective-ness and optimal application strategies.

The association of individual metals in PM2.5 with cardiovascular damage has been established in previous studies, but there are fewer studies on co-exposure to multiple metals and potential metabolic alterations in cardiovascular damage. To investigate the early cardiovascular effects of multiple metals and the mediating effects of metabolites, we conducted a panel study on young adults from 2017 Winter to 2018 Autumn in Caofeidian, China. A total of 180 serum samples were analyzed for metabolomic profiles using liquid chromatography-mass spectrometry. The associations between personal metal exposure, metabolite levels, and indicators of cardiovascular injury were analyzed by linear mixed-effects modeling (LME) and Bayesian kernel machine regression (BKMR). Metabolomic analyses showed 79 metabolites in the serum of healthy adults changed significantly between seasons and all metabolites were strongly associated with toxic metals. Additionally, differential metabolites were enriched in seven metabolic pathways and activated by metal exposure, such as Butanoate metabolism and Linoleic acid metabolism. BKMR model interpreted that the overall effect of metals mixture was negatively associated with Capryloyl glycine and Sphinganine and Sb mainly contributed to the effect. The results of mediation analysis revealed that the association between V and VEGF was mediated by Diethylhexyl with a partial proportion of 13.4%. Furthermore, the result also found the association between CerP(d18:1/26:1(17Z)) and ET-1 was mediated by TGFβ1 with a proportion of 53.4%. Our findings suggested that multiple metal exposure was associated with metabolomic changes of cardiovascular damage in young adults, and may simultaneously affect the metabolomic changes by inducing oxidative stress and inflammation.

BACKGROUND:Exposure to heavy metals represents a significant risk factor for hypertension and blood pressure disorders. Notably, current evidence indicates that the key biological processes of oxidative stress, inflammation, and endothelial dysfunction are related to metal exposure and blood pressure dysregulation, ultimately contributing to cardiovascular pathogenesis. However, their underlying biological mechanisms remain incompletely characterized. METHODS:A longitudinal study was performed among 45 healthy university students in Caofeidian, China. These participants were followed up in 4 seasons for physical examination and blood and urine samples collection between December 2017 and October 2018. we employed linear mixed effect model (LME), Bayesian kernel-machine regression (BKMR) and Machine learning (ML) to evaluate complex exposure-response relationships between multi-metal mixtures and blood pressure outcomes. Finally, we constructed the mediation analyses to analyze the potential intermediary roles of indicators in these association. RESULTS:The analysis revealed significant associations between Cr, Mn, and Mo and elevated levels of 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood pressure (all P < 0.05), respectively. BKMR and ML further demonstrated both cumulative effects and interaction patterns within the metal mixture that collectively influenced blood pressure. Additionally, 8-iso-PGF2α is significantly positively correlated with SBP and was subsequently identified as a candidate mediator. Eventually, we found that the metals of Mn, Cr, and Mo were associated with SBP mediated by 8-iso-PGF2α with 24.6 %, 17.4 %, and 20.7 %, respectively. CONCLUSIONS:These findings establish a mechanistic link between metal exposure and blood pressure dysregulation in young adults. Notably, the application of machine learning demonstrates novel utility in quantifying mixed metals on blood pressure and predicting the development of cardiovascular injury, providing a novel insight into environmental risk assessment methodologies.

INTRODUCTION:Septic shock (SS) is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation. Modified double filtration plasmapheresis (M-DFPP) is a promising therapeutic approach designed to selectively remove small-to-medium molecular weight inflammatory mediators while preserving essential plasma proteins, potentially restoring immune balance and stabilizing hemodynamics in patients with SS. METHODS:Eligible patients diagnosed with SS will be enrolled in this randomized controlled trial. Inclusion criteria include completion of early goal-directed therapy resuscitation standards within 12 h following admission to the intensive care unit and norepinephrine administration exceeding 0.5 µg/min/kg. The intervention group will receive treatment using the M-DFPP multivariate model. The primary endpoint is all-cause mortality at 28 days. Secondary endpoints will assess the efficacy of M-DFPP in reducing inflammatory mediators, evaluate changes in vasoactive drug requirements on the third day post-enrollment, and quantify improvement in organ dysfunction. CONCLUSION:Validation through well-designed, large-scale randomized controlled trials is required to clarify the optimal patient selection criteria, treatment timing, frequency, and standardized protocols for M-DFPP. This is an experimental protocol of a randomized, open-label, multicenter, parallel-controlled trial aiming to evaluate whether M-DFPP can improve survival rates in patients with SS.

Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are often used together to treat critically ill patients. This systematic review aims to assess mortality and renal recovery with this combination as reported by studies published over the past decade. We searched PubMed, Web of Science, ProQuest Health Medical Complete, Embase, and Ovid SP. Two reviewers independently screened studies and extracted data. Study quality was assessed using the Newcastle–Ottawa Scale (NOS) for non-randomized controlled trials. We performed statistical analyses with RevMan 5.4. Nineteen studies with 1,786 patients met the inclusion criteria. Of these, 1,021 patients were in the ECMO-alone group (495 deaths, 48.5,

Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.

Objective This study aimed to examine the clinical and multimodal ultrasonic characteristics differences between carotid web (CW) and CW with plaque as well as the potential risk factors for stroke caused by CW. Methods We retrospectively enrolled patients diagnosed with CW by CTA or high-resolution MRI (HRMRI) and simultaneously underwent contrast enhanced ultrasound (CEUS) and superb microvascular imaging examinations from January 2015 to October 2022. The CW angle was measured using computer-aided software. The variations between CW and CW with plaque were evaluated, and univariable and multivariable logistic regressions were utilized to identify possible risk predictors for stroke caused by CW. Results Two hundred ninety-nine patients with an average age of 60.85 (± 8.77) years were included. Sex, age, history of smoking, alcohol, hypertension, diabetes mellitus, homocysteine level, and treatment, as well as web length and thickness, luminal stenosis, location wall, number, CW angle, and CEUS enhancement, were quite different among CW and CW with plaque patients ( p < 0.05). The logistic regression analysis showed that web length was an independent predictor of luminal stenosis in CW patients. For patients with CW and plaque, plaque and web thickness, as well as plaque enhancement, were associated with stenosis. Furthermore, luminal stenosis and plaque length were risk factors for symptoms. Conclusion The multimodal ultrasonic and clinical manifestations of CW and CW with plaque are quite different. Web length is an independent risk factor for carotid artery stenosis in CW patients, whereas luminal stenosis and plaque length were risk factors for symptoms in CW with plaque patients. Critical relevance statement Exploring the similarities and differences between the carotid web and the carotid web with plaque, based on the stereo-geometric spatial position relationship and hemodynamic changes, may provide further insights into the underlying mechanisms of stroke occurrence caused by the carotid web. Key points 1. Multimodal ultrasonic and clinical manifestations of carotid web and carotid web with plaque are substantially different. 2. A thin triangular endoluminal defect is identified as a typical feature of the web on superb microvascular imaging, and two kinds of typical ultrasonic features of CW with plaque are also identified. 3. Web length is an independent risk factor for carotid stenosis in carotid web patients, whereas luminal stenosis and plaque length are risk factors for symptoms in patients with CW and plaque. Graphical Abstract

Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear.In this study,in vivo(60 μg/day,42 days)and in vitro(0.4 μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,respectively.Our study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal flora.Desulfovibrionales-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in mice.Importantly,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn expression.In conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.

BACKGROUND:Particulate matter (PM) exposure during pregnancy may increase cardiovascular risk (CVR). However, the specific time windows of exposure contributing to this association and the potential biological mechanisms underlying it remain unclear. OBJECTIVE:To determine the sensitive time window for CVR related to PM exposure. We investigated whether levels of inflammatory biomarkers mediate the relationship between PM exposure and CVR, and examined the potential impact of an anti-inflammatory diet on this association. METHODS:From 2015 to 2021, 9294 pregnant women from three Hefei hospitals were included. We used a 1 × 1 km satellite dataset to assess PM1, PM2.5, and PM10 exposure. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured as inflammatory biomarkers. The empirical dietary inflammatory pattern (EDIP) score, based on a validated food frequency questionnaire. The CVR score was calculated using five clinical metrics based on American Heart Association criteria. RESULTS:We found a significant association between PM exposure and increased CVR score, especially during the 2nd to 8th weeks of the first trimester. For every increase of 10-μg/m3 of PM1, PM2.5, and PM10, there was an associated increase in CVR of 0.51 (95%CI: 0.21, 082), 0.25 (95% CI: 0.11 to 0.39), and 0.29 (95% CI: 0.09 to 0.37), respectively. Mediation analysis revealed that the proportion of the association between PM1, PM2.5, and PM10 exposure and CVR mediated by inflammatory biomarkers was 24.3%, 22.4%, and 20.1%, respectively. Stratified analyses showed no positive correlation between PM exposure and CVR in the anti-inflammatory diet (low EDIP) group. The β coefficients were 0.52 for PM1 (95% CI: -0.06 to 1.11), 0.31 for PM2.5 (95% CI: -0.04 to 0.79), and 0.25 for PM10 (95% CI: -0.03 to 0.54). CONCLUSIONS:PM exposure, particularly during weeks 2-8 of pregnancy, correlates with CVR, partly mediated by levels of inflammatory biomarkers. An anti-inflammatory diet mitigates CVR associated with PM exposure.

To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

Benzene is a common contaminant in the workplace and wider environment, which induces hematotoxicity. Our previous study has implicated that lncRNAs mediated apoptosis and autophagy induced by benzene. Nevertheless, the roles of extracellular vesicle(EVs)-derived lncRNAs in benzene toxicity are unknown. However, the role of EVs and EVs-derived lncRNAs in benzene-induced toxicity remains unclear. In this research, we explored the function of EVs and EVs-derived lncRNAs in cell-cell communication through benzene-induced apoptosis and autophagy. Our findings demonstrated that EVs derived from 1,4-BQ-treated cells treated cells and coculture with 1,4-BQ-treated cells enhanced apoptosis and autophagy via regulating the pathways of PI3K-AKT-mTOR and chaperone-mediated autophagy. Treating with GW4869 in 1,4-BQ-treated cells significantly inhibited EV secretion, which reduced apoptosis and autophagy. Furthermore, we identified a set of differentially expressed autophagy- and apoptosis-related lncRNAs using EVs-derived lncRNA sequencing. Among them, 8 candidate lncRNAs were upregulated in EVs derived from 1,4-BQ-treated cells, as determined by lncRNA sequencing and qRT-PCR. Importantly, these lncRNAs were also increased in the serum EVs of benzene-exposed workers. 1,4-BQ-treated cells released EVs that transfer differentially expressed lncRNAs, thereby inducing apoptosis and autophagy in the recipient cells. The above results support the hypothesis that EVs-derived lncRNAs participate in intercellular communication during benzene-induced hematotoxicity and function as potential biomarkers for risk assessment of benzene-exposed workers.

The intestinal microbiota is associated with the development of benzene-induced hematopoietic toxicity. Modulation of intestinal homeostasis by probiotic supplementation has been considered an effective strategy to prevent adverse health effects. However, the role and mechanism of probiotics in benzene-induced hematopoietic toxicity are unclear. After 45 days of exposure, benzene caused bone marrow hematopoietic toxicity in mice. Furthermore, we found that benzene altered the intestinal barrier in mice, leading to an increase in the abundance of Bacteroidaceae and the activation of systemic inflammation. Interestingly, Fe2+ accumulation, lipid peroxidation, and differential expression of ferroptosis proteins were observed in the intestinal tissues of benzene-exposed mice. After fecal microbiota transplantation, stool microbes from benzene-exposed mice led to the development of intestinal ferroptosis in recipient mice. In particular, oral probiotics significantly reversed elevated Bacteroidaceae and intestinal ferroptosis, ultimately improving benzene-induced hematopoietic damage. We further used the benzene metabolite 1,4-BQ to treat human normal colonic epithelial cells (NCM460) and intervened with the ferroptosis inhibitor liproxstatin-1 (Lip-1) to validate the relationship between intestinal ferroptosis and inflammation. The results showed that 1,4-BQ treatment resulted in increased intracellular ROS levels and abnormal expression of ferroptosis proteins and the inflammatory factors IL-5 and IL-13. However, the use of Lip-1 significantly inhibited oxidative stress, ferroptosis, and inflammation in NCM460 cells. This result suggested that ferroptosis might be involved in benzene-induced hematopoietic toxicity by mediating Th2-type systemic inflammation. Overall, these findings revealed a role for Bacteroidaceae-intestinal ferroptosis-inflammation in benzene-induced hematopoietic toxicity and highlighted that probiotics could be a promising strategy to prevent adverse hematologic outcomes.

BACKGROUND:Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear. OBJECTIVES:We aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations. METHODS:A total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones. RESULTS:Perfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (β) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, β = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)]. CONCLUSIONS:Prenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH.

Long-term benzene exposure is harmful and causes hematopoietic dysfunction. However, the mechanism of benzene hematopoietic toxicity is still unclear. Acyl-CoA Synthetase Long-Chain Family Member 1 (ACSL1) has been found to participate in the progress of a variety of benign and malignant diseases, but there is no research about its effect on benzene-induced hematopoietic toxicity. Herein, We exposed C57BL/6J mice to benzene to construct an in vivo model. Human peripheral blood mononuclear cells (THP-1 cells) were treated with benzene metabolite 1, 4-BQ to construct an in vitro model. We observed that the ACSL1 expression was upregulated both in vivo and in vitro. Moreover, inhibition of ACSL1 relieved inflammation and senescence development in vitro, suggesting that ACSL1 mediates inflammation and senescence. As for the regulation mechanism of ACSL1 expression, it is closely related to hydroxymethylation modification. This was proved by hydroxymethylated DNA immunoprecipitation (hMeDIP) experiments. Furthermore, oxidative stress influenced the hydrox-ymethylation process. These results showed that benzene hematopoietic toxicity occurs through the induction of oxidative stress and thus the regulation of ACSL1 hydroxymethylation, which in turn mediates inflammation and senescence. Thus, this study might be of great significance in identifying and preventing benzene exposure in the early stage.

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 μg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

Benzene is a universal ambient pollutant. Population-based studies have shown that benzene exposure affects male fertility. However, the mechanism of benzene-induced reproductive toxicity is unknown. Here, we estab-lished a dynamic inhalation model and exposed C57BL/6J mice to 0, 10, and 50 ppm benzene (6 h/day, 6 days/ week, 7 weeks). Our study revealed that benzene exposure caused testicular injury, including structural damage to spermatogenic tubules, reduced semen quality, and decreased testosterone levels. In addition, the decrease in the global level of N6-Methyladenosine (m6A) and the change of m6A important regulatory enzymes in mice testes suggested that m6A was involved in the benzene-induced testicular injury. Further genome-wide m6A methylation analysis showed that 1469 differential m6A peaks were present in the testes of control and benzene groups, indicating that benzene exposure modulated m6A methylation in testes. Furthermore, the comprehensive analysis of m6A-sequencing and transcriptome revealed that hypermethylated Rara and its consequent reduced expression impaired the sperm production process. In particular, melatonin alleviated benzene-induced testicular injury by modulating m6A-related genes. Overall, our research provides a new idea and fundamental knowledge into the possible mechanisms of m6A modifications in benzene-induced testicular impairment, as well as a new experimental basis for benzene-induced male fertility therapy.

Exposure to fine particulate matter (PM2.5) has been associated with adverse cardiovascular outcomes. However, the effects of toxic metals in PM2.5 on cardiovascular health remain unknown. To investigate the early cardiovascular effects of specific PM2.5 metal constituents at the personal level, we conducted a panel study on 45 healthy college students in Caofeidian, China. Personal exposure concentrations and cardiovascular effect markers were monitored simultaneously within one year in four study periods. Four linear mixed-effects models were used to analyze the relationship between personal exposure to PM2.5 and 15 metal fractions (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, and Pb) with soluble CD36 (sCD36), C-reactive protein (CRP), and oxidized low-density lipoprotein (OX-LDL) levels, heart rate, and blood pressure. The concentrations of most individual metals (Mn, Cu, Zn, As, Se, Mo, Cd, Sb and Pb) were the highest in winter. Meanwhile, there were significant differences in inflammatory (sCD36 and CRP) and oxidative stress (OX-LDL) markers in the serum of participants over the four seasons. In particular, the estimated effects of personal metal exposure (such as V, As, Se, Cd, and Pb) on sCD36 and pulse pressure (PP) levels were consistently significant across the four LME models. A significant mediating role of sCD36 was also found in the relationship between personal exposure to Zn and Cr and changes in PP levels. Our findings provide clues and potential mechanisms regarding the cardiovascular effects of specific toxic constituents of PM2.5 in healthy young adults.