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Background Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis–gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. Results The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. Conclusion These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association. Highlights Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients. Graphical abstract

Laser-based powder bed fusion of metals (PBF-LB/M) is one of the most promising additive manufacturing technologies to fabricate complex-structured metal parts. However, its corresponding applications have been limited by technical bottlenecks and increasingly strict industrial requirements. Process optimization, a scientific issue, urgently needs to be solved. In this paper, a three-phase transient model based on the level-set method is established to examine the heat transfer and melt pool behavior in PBF-LB/M. Surface tension, the Marangoni effect, and recoil pressure are implemented in the model, and evaporation-induced mass and thermal loss are fully considered in the computing element. The results show that the surface roughness and density of metal parts induced by heat transfer and melt pool behavior are closely related to process parameters such as laser power, layer thickness, scanning speed, etc. When the volumetric energy density is low, the insufficient fusion of metal particles leads to pore defects. When the line energy density is high, the melt track is smooth with low porosity, resulting in the high density of the products. Additionally, the partial melting of powder particles at the beginning and end of the melting track usually contributes to pore formation. These findings provide valuable insights for improving the quality and reliability of metal additive manufacturing.

Suspended particulate matter (SPM) and sediment samples were collected from the Daliao river and Daliao river estuary (Northeast China) to clarify the changes of metal concentrations, enrichment and accumulation during the medium season, wet season and dry season, respectively. The results showed that concentrations, enrichment factor (EF) values and geo accumulation (Igₑₒ) values for metals significantly changed during the time. Generally, metal concentrations in sediments during the dry season were higher than those during the medium season and wet season. SQGs results revealed that potential toxicity for aquatic organisms may frequently happen for most of the metals during the dry season, while during the wet season and medium season, adverse effects for aquatic organisms may occasionally happen. Enrichment factor values (EF values) showed that various range of EF values for metals were found and Cd, Pb, As and Zn showed the most sever enrichment among the studied metals. Seasonal mean EF values for metals in SPM showed the following orders: Pb (2.82) > Cd (2.53) > As (2.07) > Zn (2.05) > Mn (1.94) > Co (1.23) > Fe (1.20) > Ni (1.15) > Cr (1.12) > Cu (1.00) and showed the following decreasing order: medium season > dry season > wet season, while for Mn, Cd and Pb, it shows that dry season > medium season > wet season, indicating minor enrichment for all the elements. For sediments, seasonal mean EF values for metals are showed as follows: Cd (12.80) > Pb (9.62) > As (4.11) > Zn (3.15) > Co (2.32) > Cr (2.27) > Mn (2.05) > Fe (1.87) > Ni (1.46) > Cu (1.43), indicating severe enrichment for Cd, moderate severe enrichment for Pb, moderate enrichment for As and Zn and minor enrichment for Co, Cr, Mn, Fe, Ni and Cu, respectively. Geo-accumulation index (Igₑₒ) results indicated that mean Igₑₒvalues for most of metals in sediment samples were below 0 which was classified as unpolluted except for Cd whose Igₑₒvalues was classified as unpolluted to moderately polluted sediment samples during the wet season and dry season, respectively. Igₑₒvalues in SPM for metals also showed seasonal variation and Cd, Pb, As and Zn displayed the highest seasonal mean Igₑₒvalues. Sources analysis for metals in sediments indicated that natural and anthropogenic sources both contributed to the metal accumulations in sediments and industrial and municipal sewage effluents discharged from the upstream cities may be the main anthropogenic sources for metals in the Daliao river and Daliao river estuary.

Background: Endothelial barrier dysfunction plays a key role in atherosclerosis progression. The primary pathology of obstructive sleep apnea-hypopnea syndrome is chronic intermittent hypoxia (IH), which induces reactive oxygen species (ROS) overproduction, endothelial barrier injury, and atherosclerosis. Salidroside, a typical pharmacological constituent of Rhodiola genus, has documented antioxidative, and cardiovascular protective effects. However, whether salidroside can improve IH-aggravated endothelial barrier dysfunction and atherosclerosis has not been elucidated. Methods and results: In normal chow diet-fed ApoE −/− mice, salidroside (100 mg/kg/d, p. o.) significantly ameliorated the formation of atherosclerotic lesions and barrier injury aggravated by 7-weeks IH (21%–5%–21%, 120 s/cycle). In human umbilical vein endothelial cells (HUVECs), exposure to IH (21%–5%–21%, 40 min/cycle, 72 cycles) decreased transendothelial electrical resistance and protein expression of vascular endothelial cadherin (VE-cadherin) and zonula occludens 1. In addition, IH promoted ROS production and activated ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway. All of these effects of IH were reversed by salidroside. Similar to salidroside, ROCK-selective inhibitors Y26732, and Fasudil protected HUVECs from IH-induced ROS overproduction and endothelial barrier disruption. Furthermore, salidroside increased intracellular cAMP levels, while the PKA-selective inhibitor H-89 attenuated the effects of salidroside on IH-induced RhoA/ROCK suppression, ROS scavenging, and barrier protection. Conclusion: Our findings demonstrate that salidroside effectively ameliorated IH-aggravated endothelial barrier injury and atherosclerosis, largely through the cAMP/PKA/RhoA signaling pathway.

PurposeThoracic aortic dissection (TAD) is characterized by an inflammatory response. Angiopoietin-like protein 8 (ANGPTL8) is a hormone involved in the regulation of lipid metabolism and inflammation. However, the relationship between ANGPTL8 and TAD remains unknown.MethodsThis case-control study included 78 TAD patients and 72 controls. The aortic diameter was evaluated by computed tomography and used to assess TAD severity. Circulating ANGPTL8 levels were measured by enzyme-linked immunosorbent assay. Associations of ANGPTL8 with TAD were determined by multivariate logistic regression.ResultsSerum ANGPTL8 levels were significantly higher in TAD patients compared with controls (562.50 ± 20.84 vs. 419.70 ± 22.65 pg/mL, respectively; P < 0.001). After adjusting for confounding factors, circulating ANGPTL8 levels were an independent risk factor for TAD (odds ratio = 1.587/100 pg ANGPTL8, 95% confidence interval [CI] = 1.121–2.247, P < 0.001) and positively associated with diameter (β = 1.081/100 pg ANGPTL8, 95% CI = 0.075–2.086, P = 0.035) and high-sensitivity C-reactive protein (hs-CRP) (β = 0.845/100 pg ANGPTL8, 95% CI = 0.020–1.480, P = 0.009). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8, hs-CRP, and D-dimer was 0.927, and the specificity and sensitivity were 98.46% and 79.49%, respectively. ANGPTL8 was significantly increased in TAD tissue compared with controls. In vitro, ANGPTL8 was increased in angiotensin II (AngII)-treated macrophages and vascular smooth muscle cells (VSMCs), while ANGPTL8 siRNA-mediated knockdown decreased inflammatory factors in AngII-treated macrophages and decreased apoptosis in AngII-treated VSMCs.ConclusionANGPTL8 is associated with TAD occurrence and development, which may involve pro-inflammatory effects on macrophages. ANGPTL8 combined with D-dimer and hs-CRP might be a useful clinical predictor of TAD.Trial RegistrationChiCTR-COC-17010792 http://www.chictr.org.cn/showproj.aspx?proj=18288

The coasts of Bohai Sea (BS) and Yellow Sea (YS) in China support almost one‐quarter of its population and provide more than one‐third of the national GDP. BS and YS are downwind of the Asian continental outflow in spring and winter as influenced by the East Asian monsoon. This makes the two seas important sinks of land‐based pollutants associated with the Asian continental outflow. The sixteen U.S. EPA proposed priority polycyclic aromatic hydrocarbons (PAHs) in 130 surface sediment samples collected from BS and YS were measured. Combined with our previous PAH data of 90 PM2.5 samples from the upwind areas, the sources of the PAHs in BS and YS were apportioned using positive matrix factorization (PMF) modeling. Four sources were identified: petroleum residue, vehicular emissions, coal combustion and biomass burning. Petroleum residue was the dominant contributor of PAHs in the coast of the Bohai Bay probably due to Haihe River runoff, oil leakage from ships and offshore oil fields. The contribution of vehicular emissions in BS was higher than that in YS, and the reverse was true for coal combustion and biomass burning. This difference in the source patterns in the sediments of the two seas could be attributed to the different PAH emission features of the upwind area related to demographic and economic conditions, as well as the marine geography. The ratios of selected 4–6 ring PAHs in the sediments compared well with those of the PM2.5 of the upwind areas, implicating that the particle phase PAHs in the atmosphere play an important role in the source to sink process of the pyrogenic PAHs in the region. Key Points The particle‐phase PAHs play a dominant role in the source‐to‐sink process The source pattern in sediment was responsed to origin in upwind area The BS and YS are important sink of PAHs by atmospheric continental outflow

Background Angiopoietin-like protein 8 (ANGPTL8), which is a novel hormone produced in liver and adipose tissue, is involved in regulating lipid metabolism. Patients with diabetes and coronary artery disease (CAD) have remarkably higher levels of ANGPTL8 than those with only diabetes. However, no studies have investigated the involvement of ANGPTL8 in CAD in Chinese non-diabetic individuals. Therefore, we investigated full-length circulating ANGPTL8 levels in patients with CAD and the association between ANGPT8 levels and severity of CAD in Chinese individuals without diabetes. Methods We performed a case–control study in 149 Chinese non-diabetic subjects, including 80 patients with CAD and 69 controls. The Gensini stenosis scoring system was used to assess the severity of CAD. Circulating full-length ANGPTL8 levels were measured by an enzyme-linked immunosorbent assay kit. The associations between circulating full-length ANGPTL8 levels and CAD were determined by multivariate logistic regression analysis. The association between ANGPTL8 levels and Gensini scores was determined by multivariate linear regression analysis. Results Circulating full-length ANGPTL8 levels were significantly higher in Chinese non-diabetic patients with CAD compared with controls (665.90 ± 243.49 vs 462.27 ± 151.85 pg/ml, P < 0.001). After adjusting for confounding factors, we found that circulating full-length ANGPTL8 levels were an independent risk factor for CAD (odds ratio = 2.002/100 pg ANGPTL8, 95% CI 1.430–2.803, P < 0.001) and circulating ANGPTL8 levels were positively associated with the Gensini score (β = 5.701/100 pg ANGPTL8, 95% CI 1.306–10.096, P = 0.012). Conclusions This study shows that the circulating ANGPTL8 levels are significantly increased in patients with CAD compared with controls in Chinese non-diabetic individuals. Circulating full-length ANGPTL8 levels are an independent risk factor for CAD and they are positively associated with the severity of CAD. Trial registration This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR-COC-17010792)

PurposeIntermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, has been known as a dominant cause of OSA-related endothelial dysfunction and hypertension. However, the underlying mechanism still remains unclear. Extracellular vesicles (EVs), small vesicles secreted by various cells, can be absorbed by endothelial cells and then influence vascular function. The aim of this research is to clarify whether and how EVs shedding from red blood cells (RBCs) are involved in IH-induced endothelial dysfunction.MethodsEVs were extracted by ultracentrifugation. After the identification of property and purity, EVs from IH-exposed RBCs (IH REVs) and normoxia-exposed RBCs (NOR REVs) or from OSA and non-OSA patient RBCs were utilized to treat C57BL/6 mouse aortas or human umbilical vein endothelial cells (HUVECs) for mechanistic exploration.ResultsFunctional results demonstrated that REVs from OSA patients dramatically impaired endothelium-dependent relaxations (EDRs). Similarly, in vivo and ex vivo studies showed that IH REVs caused significant endothelial dysfunction compared to control group. Further results presented that IH REVs blocked endothelial nitric oxide synthase (eNOS) phosphorylation through inhibiting PI3K/Akt pathway and enhanced endothelin-1 (ET-1) expression through activating Erk1/2 pathway in endothelial cells. Meanwhile, endothelial dysfunction caused by IH REVs was reversed by Akt activator SC79 as well as Erk kinase inhibitor PD98059, suggesting that PI3K/Akt/eNOS and Erk1/2/ET-1 pathways were implicated in IH REV-induced impaired EDRs.ConclusionsThis study reveals a novel role of REVs in endothelial dysfunction under IH and dissects the relevant mechanism involved in this process, which will help to establish a comprehensive understanding of OSA or IH-related endothelial dysfunction from a new scope.

Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular diseases. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to arteriosclerosis (AS) pathogenesis remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE -/- ) mice treated with high-fat diet (HFD) and subjected to CIH conditions was applied to mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation were confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE -/- mice treated with HFD. The gut bacteria was significantly varied in AS and AS+CIH mice compared with that in the control mice. Significantly perturbed GM profiles were detected in AS mice with and without CIH, with altered microbial α- and β- diversity and shifts in bacterial compositions at phylum and genus levels. While the difference between AS and AS+CIH was observed at different bacteria taxa levels. Aggravation of reduced Sutterella and increased Halomonas , Halomonadaceae and Oceanospirillales was noted in CIH-treated AS mice. The correlation of intestinal bacterial parameters with pathological changes in artery indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the gut microbial functions in the potential ability of replication recombination and repair proteins, glycan biosynthesis and metabolism, as well as metabolism of cofactors and vitamins were identified to be further suppressed by CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.

Background Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. Methods Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients ( n  = 184) from heterozygous FH (HeFH, n  = 376) and non-FH ( n  = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. Results Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. Conclusions Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.