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Nonsuicidal self-injury (NSSI) generally occurs in youth and probably progresses to suicide. An examination of cortical thickness differences (ΔCT) between NSSI individuals and controls is crucial to investigate potential neurobiological correlates. Notably, ΔCT are influenced by specific genetic factors, and a large proportion of cortical thinning is associated with the expression of genes that overlap in astrocytes and pyramidal cells. However, in NSSI youth, the mechanisms underlying the relations between the genetic and cell type-specific transcriptional signatures to ΔCT are unclear. Here, we studied the genetic association of ΔCT in NSSI youth by performing a partial least-squares regression (PLSR) analysis of gene expression data and 3D-T1 brain images of 45 NSSI youth and 75 controls. We extracted the top-10 Gene Ontology terms for the enrichment results of upregulated PLS component 1 genes related to ΔCT to conduct the cell-type classification and enrichment analysis. Enrichment of cell type-specific genes shows that cellular component morphogenesis of astrocytes and excitatory neurons accounts for the observed NSSI-specific ΔCT. We validated the main results in independent datasets to verify the robustness and specificity. We concluded that the brain ΔCT is associated with cellular component morphogenesis of astrocytes and excitatory neurons in NSSI youth.
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Astrocitos , Conducta Autodestructiva , Humanos , Adolescente , Encéfalo , Neuronas , MorfogénesisRESUMEN
Heavy metals (HMs) pose significant risks to human health and the environment. Identifying the sectors that play a significant role in the transmission of HMs has rarely been considered and represents an efficient method to control and manage HMs. By combining atmospheric HM emission inventories, the multi-regional input-output approach, and a betweenness-based method, this study revealed the transmission of HMs (comprehensively evaluated by the Heavy Metal Pollution Load, HMPL) in 2017. In 2017, 119.86 million tons of HMPL were transmitted through China's supply chain, and Cr was the main contributor to HMPL transmission. The results suggest that metal smelting is the primary contributor to HMPL transmission, and metal smelting in Jiangsu, Hebei, Henan, Shandong, and Anhui are the top five critical nodes. These results suggest that the sector's role changes dramatically with respect to HM control under this perspective. The role of HM emission-intensive sectors changed the most, as their production-based HMPLs accounted for 84% of the total HMPL; however, the HMPL transmitted by these sectors accounted for only 45% of the total. The critical HMPL transmission sectors identified in this study provide a basis for policy-making from a transmission perspective.
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Metales Pesados , Contaminantes del Suelo , Humanos , Metales Pesados/análisis , Contaminación Ambiental , China , Monitoreo del Ambiente , Medición de RiesgoRESUMEN
OBJECTIVE: To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart catheterization (RHC) and intravascular ultrasound (IVUS). METHOD: A total of 60 patients underwent RHC and IVUS examinations. Of these, 27 patients were diagnosed with PAH associated with connective tissue diseases (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group), and 15 patients were without PAH (control group). The hemodynamics and morphological parameters of pulmonary vessels in PAH patients were assessed using RHC and IVUS. RESULTS: There were statistically significant differences in right atrial pressure (RAP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) values between the PAH-CTD group, other-types-PAH group, and the control group (P < .05). No statistically significant difference was noticed in pulmonary artery wedge pressure (PAWP) and cardiac output (CO) values between these three groups (P > .05). The mean wall thickness (MWT), wall thickness percentage (WTP), pulmonary vascular compliance, dilation, elasticity modulus, stiffness index ß, and other indicators were significantly different between these three groups (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in PAH-CTD group and other-types-PAH group were lower than those in control group, while the average levels of elastic modulus and stiffness index ß were higher than those in control group. CONCLUSION: Pulmonary vascular performance deteriorates in PAH patients, and the performance is better in PAH-CTD patients than in other types of PAH.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hemodinámica , Arteria Pulmonar , PulmónRESUMEN
Heavy metals (HMs) exhibit significant toxicity and can lead to a range of health issues. Certain HMs share common emission sources, necessitating an exploration of the nexus among various HMs for achieving collaborative reductions. Considering the efficacy and feasibility of industrial modification to environmental pressures, this paper proposes a novel nexus-based optimization approach based on nexus analysis, multi-region input-output (MRIO) table, and multi-objective optimization to mitigate atmospheric HMs. The atmospheric HM emission inventory in 2017 is first compiled. Subsequently, the Integrated Nexus Strength of HMs Risk (HMR-INS) is proposed and employed to determine the range of sectoral output variations. Finally, a multi-objective optimization approach is employed based on the MRIO table in 2017. Compared with the traditional optimization method, the proposed approach performs better regarding HM-related risks and total output, leading to a 1.9 million tons increase in reduction on HM-related risks and a 1.37 trillion yuan increment in total output. Some further analyses are also given to provide feasible solutions for industrial modification, which considers both the economic efficiency and the stability of the industrial structure.
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Objective: To investigate how serum GDF-15 concentration affects pulmonary artery hemodynamics and pulmonary vascular morphological changes in patients with pulmonary arterial hypertension. Methods: A total of 45 patients admitted to our hospital from December 2017 to December 2019, were selected for the study. Pulmonary vascular hemodynamics and pulmonary vascular morphology were detected by RHC and IVUS. Serum GDF-15 levels were detected by enzyme-linked immunosorbent assay (ELISA). Based on the concentration of GDF-15, the patients were divided into two groups-the normal GDF-15 group (GDF-15 <1,200â pg/ml, 12 cases) and the elevated GDF-15 group (GDF-15 ≥1,200â pg/ml, 33 cases). A statistical analysis was performed to compare the effects of normal blood GDF-15 levels and high serum GDF-15 levels on hemodynamics and pulmonary vascular morphology in each group of patients. Results: The average levels of RVP, sPAP, dPAP, mPAP, and PVR in patients with elevated GDF-15 levels were higher than those in patients with normal GDF-15 levels. The difference between the two groups was statistically significant (P < 0.05). The average levels of Vd, elastic modulus, stiffness index ß, lesion length, and PAV in the normal GDF-15 group were lower than those in the elevated GDF-15 group. The average levels of compliance, distensibility, and minimum l umen area were higher than those in the elevated GDF-15 group. The difference between the two groups was statistically significant (P < 0.05). The survival analysis results showed that the 1-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 100% and 87.9%, respectively, and that the 3-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 91.7% and 78.8%, respectively. The survival rates of the two groups were compared by the Kaplan Meier method, and the difference was not statistically significant (P > 0.05). Conclusion: Patients with pulmonary arterial hypertension with elevated GDF-15 levels have higher pulmonary arterial pressure, higher pulmonary vascular resistance, and more serious pulmonary vascular lesions, which are potentially more harmful. There was no statistically significant difference in survival rates among patients with different serum GDF-15 levels.
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Tetrabromobisphenol A (TBBPA) is a widely used plastic additive with high bioaccumulation potential and toxicity on both humans and wildlife. Currently, research on its ecotoxicity and the underlying mechanism is limited. Using common carp (Cyprinus carpio), we evaluated the toxicity of TBBPA, especially focusing on its alteration of a key metabolism-related pathway aryl hydrocarbon receptor (AHR), using in vivo/vitro assays and in silico simulation. The 96 h LC50 of TBBPA of common carp was 4.2 mg/L and belonged to the acute toxic level II. The bioaccumulation potential of TBBPA follows the role of liver > gill > brain and varies between 3- and 14-day exposure. On the AHR pathway respect, as expected, the metabolism-related cyp1a1 and cyp1b1 were upregulated in the liver and brain. Ahr2, the receptor, was also upregulated in the brain under TBBPA exposure. The alteration of gene expression was tissue-specific while the difference between 3- or 14-day exposure was minor. AHR inhibition assay indicated the 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR transactivation can be inhibited by TBBPA suggesting it is not a potent agonist but a competitive antagonist. In silico analysis indicated TBBPA can be successfully docked into the binding cavity with similar poses but still have AHR-form-specific interactions. Molecular dynamics simulation proved TBBPA can be more flexible than the coplanar ligand TCDD, especially in ccaAHR1b with greater root-mean-square deviation (RMSD), of which TCDD-induced transactivation seemed not to be blocked by TBBPA. This research increased the understanding of TBBPA toxicity and alteration of the AHR pathway, and pointed out the need to perform additional toxicology evaluation of emerging contaminants, especially on non-model species.
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Carpas , Dibenzodioxinas Policloradas , Animales , Humanos , Receptores de Hidrocarburo de Aril/metabolismo , Carpas/metabolismo , Hígado/metabolismo , Dibenzodioxinas Policloradas/metabolismo , Citocromo P-450 CYP1A1/metabolismoRESUMEN
Lipotoxicity contributes to insulin resistance and dysfunction of pancreatic ß-cells. Insulin promotes 3T3-L1 preadipocyte differentiation and facilitates glucose entry into muscle, adipose, and other tissues. In this study, differential gene expression was analyzed using four datasets, and taxilin gamma (TXLNG) was the only shared downregulated gene in all four datasets. TXLNG expression was significantly reduced in obese subjects according to online datasets and in high-fat diet (HFD)-induced insulin-resistant (IR) mice according to experimental investigations. TXLNG overexpression significantly improved IR induced by HFD in mouse models by reducing body weight and epididymal adipose weight, decreasing mRNA expression of pro-inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), and reducing adipocyte size. High-glucose/high-insulin-stimulated adipocytes exhibited decreased TXLNG and increased signal transducer and activator of transcription 3 (STAT3) and activating transcription factor 4 (ATF4). IR significantly decreased glucose uptake, cell surface glucose transporter type 4 (GLUT4) levels, and Akt phosphorylation, while increasing the mRNA expression levels of IL-6 and TNF-α in adipocytes. However, these changes were significantly reversed by TXLNG overexpression, while they were exacerbated by TXLNG knockdown. TXLNG overexpression had no effect on ATF4 protein levels, while ATF4 overexpression increased ATF4 protein levels. Furthermore, ATF4 overexpression notably abolished the improvements in IR adipocyte dysfunction caused by TXLNG overexpression. In conclusion, TXLNG improves IR in obese subjects in vitro and in vivo by inhibiting ATF4 transcriptional activity.