Tribocorrosion Behavior of NiCoCrMoCu Alloys Containing Different Carbides in Acidic Media at Various Applied Loads and Sliding Speeds.

In this study, the ball-on-disk sliding wear and tribocorrosion behavior in the H2SO4 and HCl solution of NiCoCrMoCu alloys with carbon additions of 0.2, 1, 1.5, and 2 wt.% with the Al2O3 ball as a counterpart was investigated systematically. Obvious tribocorrosion antagonistic effects were found after wear in both aqueous solutions. Compared with dry sliding wear conditions, the lubrication effect of the aqueous solution significantly reduces the wear rate of the alloy, and the reduction effect in the H2SO4 aqueous solution was more obvious than that in HCl. The antagonistic effects of the 0.2C and 1C alloys decrease with the load and sliding rate, while those of the 1.5C and 2C alloys increase. The (coefficient of friction) COF and wear rate under different loads and sliding rates were analyzed using the response surface analysis (RSM) method. It was found that the COF mainly showed dependence on the sliding rate, while the wear rate showed dependence on load and sliding speed.

Optimizing the cell compatibility and mechanical properties in TiZrNbTa medium-entropy alloy/ß-Ti composites through phase transformation.

Medium-entropy alloys (MEAs) typically exhibit outstanding mechanical properties, but their high Young's modulus results in restricted clinical applications. Mismatched Young's modulus between implant materials and human bones can lead to "stress shielding" effects, leading to implant failure. In contrast, ß-Ti alloys demonstrate a lower Young's modulus compared to MEAs, albeit with lower strength. In the present study, based on the bimodal grain size distribution (BGSD) strategy, a series of high-performance TiZrNbTa/Ti composites are obtained by combining TiZrNbTa MEA powders with nano-scale grain sizes and commercially pure Ti (CP-Ti) powders with micro-scale grain sizes. Concurrently, Zr, Nb, and Ta that are ß-Ti stabilizer elements diffuse into Ti, inducing an isomorphous transformation in Ti from the high Young's modulus α-Ti phase to the low Young's modulus ß-Ti phase at room temperature, optimizing the mechanical biocompatibility. The TiZrNbTa/ß-Ti composite demonstrates a yield strength of 1490 ± 83 MPa, ductility of 20.7 % ± 2.9 %, and Young's modulus of 87.6 ± 1.6 GPa. Notably, the yield strength of the TiZrNbTa/ß-Ti composite surpasses that of sintered CP-Ti by 2.6-fold, and its ductility outperforms TiZrNbTa MEA by 2.3-fold. The Young's modulus of the TiZrNbTa/ß-Ti composite is reduced by 28 % and 36 % compared to sintered CP-Ti and TiZrNbTa MEA, respectively. Additionally, it demonstrates superior biocompatibility compared to CP-Ti plate, sintered CP-Ti, and TiZrNbTa MEA. With a good combination of mechanical properties and biocompatibility, the TiZrNbTa/ß-Ti composite exhibits significant potential for clinical applications as metallic biomaterials. STATEMENT OF SIGNIFICANCE: This work combines TiZrNbTa MEA with nano-grains and commercially pure Ti with micro-grains to fabricate a TiZrNbTa/ß-Ti composite with bimodal grain-size, which achieves a yield strength of 1490 ± 83 MPa and a ductility of 20.7 % ± 2.9 %. Adhering to the ISO 10993-5 standard, the TiZrNbTa/ß-Ti composite qualifies as a non-cytotoxic material, achieving a Class 0 cytotoxicity rating and demonstrating outstanding biocompatibility akin to commercially pure Ti. Drawing on element diffusion, Zr, Nb, and Ta serve not only as solvent atoms to achieve solid-solution strengthening but also as stabilizers for the transformation of the ß-Ti crystal structure. This work offers a novel avenue for designing advanced biomedical Ti alloys with elevated strength and plasticity alongside a reduced Young's modulus.

Retention behavior of nucleosides and nucleobases on a 3 µm undecylenic acid-functionalized silica column in per aqueous liquid chromatography and hydrophilic interaction liquid chromatography separation modes.

A 3 µm undecylenic acid-functionalized stationary phase (UAS) was prepared for the separation of nucleosides and nucleobases using per aqueous liquid chromatography (PALC) and hydrophilic interaction liquid chromatography (HILIC). The retention behaviors of nucleosides and nucleobases in PALC and HILIC modes were explored by adjusting parameters such as water content, buffer concentration, pH of the mobile phase and column temperature. The experimental data and separation chromatogram demonstrated that PALC could provide retention comparable to that of HILIC for nucleosides and nucleobases. Comparative studies using diluted adenosine solutions evaluated theoretical plates and peak shape for the same retention factors (between 0.25 and 5.0) in PALC and HILIC. There was no buffer component in the mobile phases used to operate the comparisons. HILIC mode is more efficient for adenosine than PALC mode at low retention factors. It's the exact opposite phenomenon for high retention factors. It is proposed that the mass transfer of adenosine between the UAS, the water-rich layer and the ACN-rich mobile phase in HILIC is relatively slow. Given the significant use of toxic ACN in HILIC, PALC emerges as a safer and more effective alternative for separating nucleosides and nucleobases.

Analysis of the Relationship Between the Changes of Serum SAA, LP-PLA2, sCD40L and Carotid Atherosclerosis Plaque in Patients with Acute Cerebral Infarction.

Objective: To explore the relationship between Serum amyloid protein A(SAA), lipoprotein-associated Phospholipase A2 (Lp-PLA2) and soluble CD40 ligand (sCD40L) in detecting the stability of carotid Atherosclerosis plaque. Methods: We examined 90 patients admitted to our hospital with acute cerebral infarction from July 2020 to December 2022. Carotid artery ultrasounds were performed for all of them. These patients were then divided into two groups: the stable plaque group (45 cases) and the unstable plaque group (45 cases), based on the ultrasound results. Additionally, we included a control group of 30 healthy individuals from our hospital. We collected fasting blood samples from the patients upon admission and used enzyme-linked immunosorbent assays to measure the mass concentrations of sCD40L, Lp-PLA2, and SAA in their serum. The results of these biomarkers were compared and analyzed to assess potential associations with plaque stability in patients with cerebral infarction. Results: Comparison of general clinical data and laboratory data: except for High-density lipoprotein, there was a statistical difference between the control group and the cerebral infarction group (P < .05), there was no statistical difference in gender, smoking history, drinking history and age (P > .05). Compared with the control group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in patients with stable and unstable plaques increased significantly (P < .05); Compared with the stable plaque group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in unstable plaque patients increased with statistical significance (P < .05). Correlation analysis shows that the mass concentrations of sCD40L, Lp-PLA2, and SAA are positively correlated with the stability of carotid artery plaques. SCD40L, Lp-PLA2 and SAA have certain diagnostic significance in the subject's working characteristic curve (Receiver operating characteristic) as a marker molecule for the diagnosis of unstable plaque. sCD40L (AUC=0.883) has more diagnostic value than SAA (AUC=0.756) and Lp-PLA2 (AUC=0.826). A binary logistic regression analysis was conducted using the stability of carotid artery plaques as the dependent variable and sCD40L, Lp-PLA2, and SAA as independent variables. The results showed that elevated serum sCD40L, Lp-PLA2, and SAA were independent risk factors for unstable carotid artery plaques (P < .05). Conclusion: The concentrations of sCD40L, Lp-PLA2 and SAA are closely related to the formation and type of carotid Atherosclerosis plaque in patients with acute cerebral infarction. This has potentially important clinical implications for the management and prevention of cardiovascular disease.

A randomized controlled trial of spinal morphine with an enhanced recovery pathway and its effect on duration of analgesia after cesarean delivery.

BACKGROUND: Intrathecal morphine is frequently administered after cesarean delivery to provide pain relief lasting up to 24 h. An enhanced recovery after cesarean pathways reduces the amount of postoperative opioids needed. The ideal dose of intrathecal morphine when combined with a pathway has not been determined. METHODS: This was a non-inferiority trial in 72 healthy women undergoing a scheduled cesarean delivery. Women were randomized to receive either 50 mcg, 150 mcg, or 250 mcg of intrathecal morphine during spinal anesthesia, with a standardized postoperative enhanced recovery pathway. The time to request supplemental opioids was the primary outcome. Secondary outcomes included pain scores, side effects, and quality of recovery at 24 h. RESULTS: The duration of analgesia with 50 mcg of morphine (median 24.5 h [IQR: 3.5-34.4]) was inferior to 150 mcg (29.4 h [24.5-72]), and both doses were inferior to 250 mcg (32 h [30.5-72]). Women who received 50 mcg morphine had higher pain scores than the other doses, received more supplemental opioids, and had lower quality recovery scores. The secondary outcomes between 150 mcg and 250 mcg were similar. Side effects were similar among all groups. 63% of women who received 250 mcg remained opioid-free at 72 h, compared to 150 mcg (52%) and 50 mcg (30%). CONCLUSIONS: The duration of analgesia using intrathecal morphine with an enhanced recovery pathway was longer with 250 mcg than with lower doses, and side effects were similar. 50 mcg provided inferior pain relief over 24 h. More than half of our patients avoided additional opioids for up to 72 h with either 150 mcg or 250 mcg doses. REGISTRATION: Clinical trial number NCT05069012.

Enhanced Anti-Corrosion Performance of Co-Cr-Mo Alloy in Molten Al by Prior Oxidation Treatment.

Co-based alloys are promising alternatives to replace the currently used tool steels in aluminum die-casting molds for producing sophisticated products. Although the reaction is significantly less severe compared to that of tool steels, bare Co-29Cr-6Mo (CCM) alloy is still gradually corroded under molten Al, leading to the local failure of the alloy due to the formation of intermetallic compounds between the matrix and molten Al. This study indicated that prior oxidation treatment at 750 °C on CCM alloy is beneficial in enhancing the corrosion resistance of the alloy to molten Al. The is more pronounced in the alloy after a longer oxidation treatment. However, after oxidation for longer than 24 h, the protectiveness of the film cannot be enhanced anymore. In addition, even after the full failure of the oxide film, the thickness loss rate of a sample with prior oxidation treatment is much lower than that of a bare sample. This can be attributed to the fact that network-aligned oxide particles of the cone structure boundary inhibit both the outwards movements of alloying elements and the dissolution of the intermetallic layer.

Effect of Heat Treatment States of Feedstock on the Microstructure and Mechanical Properties of AA2219 Layers Deposited by Additive Friction Stir Deposition.

This study is the first to research the microstructure and mechanical properties of the workpiece after additive friction stir deposition (AFSD) of the feedstock at different heat treatment stages. AA2219 aluminum alloys with three different heat treatment stages were selected as the feedstock, and alloys with dense structure were successfully prepared by the additive friction stir deposition AFSD process. Experimental results show that AFSD exhibits an excellent ability to refine grains and improve the uniform distribution of precipitates in the second phase, thereby improving the plasticity of AA2219 alloy after the AFSD process. Because of the continuous dynamic recrystallization (CDRX) in the AA2219 alloy during AFSD, the grain size after the AFSD process is independent of the initial feedstock grain size for three samples. The equilibrium phase (θ) size is genetically related to the initial size of the second-phase particles in the feedstock. Due to grain refinement and dislocation strengthening, the yield strength of AA2219-casting increased significantly from 79.8 MPa to 124.1 MPa after AFSD. The yield strength of the AA2219-T4 decreases slightly from 151.8 MPa to 140.4 MPa after AFSD. The precipitation of the second phase leads to a decrease in solid solution strengthening and dislocation strengthening. However, grain refinement strengthening partially offsets this reduction. The yield strength of AA2219-T87 decreased from 398.5 MPa to 147.2 MPa after AFSD. As such, grain refinement strengthening and solid solution strengthening by the AFSD process are much smaller than the yield strength lost by precipitation strengthening and dislocation strengthening.

Enhanced Mechanical Properties of Cast Cu-10 wt%Fe Alloy via Single-Pass Friction Stir Processing.

In this study, Cu-10 wt% Fe alloy in as-cast state was modified using friction stir processing (FSP). The microstructure evolution of Cu-10 wt% Fe alloys in different states was characterized in detail using scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The results show that due to dynamic recrystallization, the FSPed Cu-10 wt% Fe alloy obtained a uniformly equiaxed ultrafine microstructure with low density of dislocation, high proportion of high-angle grain boundaries (HAGBs), and high degree of recrystallization. Fine equiaxed grains with an average size of 0.6 µm were produced after FSP. Many fine-precipitate Fe-phases with an average size of 20 nm were uniformly distributed in the Cu matrix. The FSPed samples possessed excellent mechanical properties, such as high Vickers hardness (163.5 HV), ultimate tensile strength (538.5 MPa), and good elongation (16%). This single-pass FSP method does not require subsequent aging treatment and provides a simple and efficient way to improve the properties of Cu-Fe alloys.

Changes in the gut microbiota of patients with Graves' orbitopathy according to severity grade.

BACKGROUND: To explore the changes of gut microbiota in Graves' orbitopathy (GO) patients of different severity grades and to identify the pathogenic bacteria of GO and the associated mechanism. METHODS: A total of 18 healthy controls and 62 GO patients were recruited. The baseline information and faecal samples of all subjects were collected for gut microbiota analysis and metabolic function prediction analysis. 16SrDNA sequencing was used for microbial diversity detection. The operational taxonomic unit (OTU) was divided using the Mothur software, and the dominant microbiota was analysed. OTU number, Chao1 index, ACE index, and Shannon index of microbiota in faecal samples were analysed using the QIIME1.9.0 software. The relative abundance of microbiota in faecal samples was analysed through principal component analysis (PCA) using the Canoco Software 5.0. The metabolic function of microbiota in faecal samples was predicted using PICRUSt 2.0. RESULTS: There was no remarkable difference in gut microbiota diversity between groups; however, the gut microbial community and dominant microbiota significantly differed among groups. Klebsiella_pneumoniae was deemed the potentially pathogenic bacteria of GO, and its abundance was positively correlated with disease severity. The metabolic prediction results revealed that inorganic nutrition metabolism, fatty acid and lipid degradation, electron transfer, aromatic compound degradation, and alcohol degradation were notably different between groups with high and low abundance of Klebsiella_pneumoniae and among groups with different GO severity grades, thereby showing a positive correlation with GO clinical risks. CONCLUSIONS: Klebsiella_pneumoniae was a potential GO-related pathogen, which may regulate the metabolic pathways to affect GO progression.

Influence of Preheating Temperature on the Microstructure and Mechanical Properties of 6061/TA1 Composite Plates Fabricated by AFSD.

In this study, composite plates of 6061/TA1 were successfully manufactured using additive friction stir deposition (AFSD). The impact of preheating temperatures (room temperature, 100 °C, 200 °C) on the interfacial microstructure and interface mechanical properties at various deposition zones was studied. The results showed that as the preheating temperature increased or when the deposit zone shifted from the boundary to the center, the diffusion width of Al and Ti increased, accompanied by an increase in bonding shear strength. Moreover, in the boundary zone of the sample preheated at room temperature (P-RT), only mechanical bonding was observed, resulting in the lowest bonding shear strength. Conversely, the other samples exhibited a combination of mechanical and metallurgical bonding. Under the preheating temperature of 200 °C, interfacial intermetallic compounds were observed near the center zone, which exhibited the highest bonding shear strength.

Influences of Fe Content and Cold Drawing Strain on the Microstructure and Properties of Powder Metallurgy Cu-Fe Alloy Wire.

To study the effects of Fe content and cold drawing strain on the microstructure and properties, Cu-Fe alloys were prepared via powder metallurgy and hot extrusion. Scanning electron microscopy was applied to observe the Fe phase, and the ultimate tensile strength was investigated using a universal material testing machine. Alloying with an Fe content below 10 wt.% formed a spherically dispersed Fe phase via the conventional nucleation and growth mechanism, whereas a higher Fe content formed a water-droplet-like Fe phase via the spinodal decomposition mechanism in the as-extruded Cu-Fe alloy. Further cold drawing induced the fiber structure of the Fe phase (fiber strengthening), which could not be destroyed by subsequent annealing. As the Fe content increased, the strength increased but the electrical conductivity decreased; as the cold drawing strain increased, both the strength and the electrical conductivity roughly increased, but the elongation roughly decreased. After thermal-mechanical processing, the electrical conductivity and strength of the Cu-40Fe alloy could reach 51% IACS and 1.14 GPa, respectively. This study can provide insight into the design of high-performance Cu-Fe alloys by tailoring the size and morphology of the Fe phase.

A facile approach to undecylenic acid-functionalized stationary phases for per aqueous liquid chromatography.

Green chromatography techniques using low-toxic mobile phase are getting increasingly attention in recent years. The core is developing stationary phases that possess adequate retention and separation under the mobile phase of high content water. Using thiol-ene click chemistry, an undecylenic acid-bonded silica stationary phase (UAS) was prepared in a facile manner. Elemental analysis (EA), solid-state 13C NMR spectroscopy and Fourier transform infrared spectrometry (FT-IR) confirmed the successful preparation of UAS. The synthesized UAS was employed for per aqueous liquid chromatography (PALC), which uses little organic solvent during separation. Due to the hydrophilic carboxy, thioether group and hydrophobic alkyl chains of the UAS, various categories of compounds (including nucleobases, nucleosides, organic acids and basic compounds) with different properties can achieve enhanced separation under the mobile phase of high content water compared with commercial C18 and silica stationary phases. Overall, our present UAS stationary phase shows excellent separation ability toward highly polar compounds and meets the requirements of green chromatography.

Utility of isolated-check visual evoked potential technique in dysthyroid optic neuropathy.

PURPOSE: To analyze the utility of isolated-check visual evoked potential (icVEP) for discriminating between eyes with dysthyroid optic neuropathy (DON) and eyes with thyroid-associated ophthalmopathy (TAO) but not DON. METHODS: Forty-three eyes with TAO but not DON (as non-DON), fifty-three eyes with DON, and sixty healthy eyes (as controls) were included. Comprehensive ophthalmic examinations, including best-corrected visual acuity, refraction, color vision test, intraocular pressure measurement, slit-lamp biomicroscopy, ophthalmoscopy, RAPD, exophthalmometry measurements, pVEP test, icVEP test, standard automated perimetry, and clinical activity score classification of TAO, as well as demographic information, were collected and analyzed. RESULTS: In the DON group, the signal-to-noise ratio (SNR) value of icVEPs decreased significantly compared with that of the non-DON group as well as control (p < 0.05). The SNR values under 8%, 16% and 32% depth of modulation (DOM) were significantly negatively correlated with BCVA (p < 0.05, r = - 0.9 ~ - 0.6), papilledema (Y/N) (p < 0.05, r = - 0.8 ~ 0.4) and DON (Y/N) (p < 0.001, r = - 0.7 ~ - 0.5). The 8% DOM of icVEP had the largest area under the receiver operating characteristic curve (AUC) (0.842) for discriminating DON from non-DONs. Meanwhile, decision curve analysis (DCA) showed that patients clinically benefit most from 8% DOM of icVEP. Furthermore, the 8% DOM of icVEP combing with papilledema (Y/N) and BCVA (Model 1) has significantly larger AUC than the 8% DOM of icVEP (p = 0.0364), and has better clinical benefit in DCA analysis. CONCLUSIONS: The SNR of 8% DOM from icVEP may represent a significant ancillary diagnostic method for DON detection. Furthermore, icVEP combined with papilledema (Y/N) and BCVA should be considered as a diagnostic model in future clinical practice.

Subacute exposure to dechlorane 602 dysregulates gene expression and immunity in the gut of mice.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)- 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

Exposure to dechlorane 602 induces perturbation of gut immunity and microbiota in female mice.

The homeostasis of gut immunity and microbiota are associated with the health of the gut. Dechlorane 602 (Dec 602) with food web magnification potential has been detected in daily food. People who were orally exposed to Dec 602 may encounter increased risk of health problems in the gut. In order to reveal the influence of short-term exposure of Dec 602 on gut immunity and microbiota, adult female C57BL/6 mice were administered orally with Dec 602 (low/high doses: 1.0/10.0 µg/kg body weight per day) for 7 days. Lymphocytes were examined by flow cytometry. Gut microbiota was measured by 16S rRNA gene sequencing. Results showed that fecal IgA was upregulated after exposure to the high dose of Dec 602, suggesting that there might be inflammation in the gut. Then, changes of immune cells in mesenteric lymph nodes and colonic lamina propria were examined. We found that exposure to the high dose of Dec 602 decreased the percentages of the anti-inflammatory T regulatory cells in mesenteric lymph nodes. In colonic lamina propria, the production of gut protective cytokine interleukin-22 by CD4+ T cells was decreased, and a decreased trend of interleukin-22 production was also observed in type 3 innate lymphoid cells in the high dose group. Furthermore, an altered microbiota composition toward inflammation in the gut was observed after exposure to Dec 602. Additionally, the altered microbiota correlated with changes of immune parameters, suggesting that there were interactions between influenced microbiota and immune parameters after exposure to Dec 602. Taken together, short-term exposure to Dec 602 induced gut immunity and microbiota perturbations, and this might be the mechanisms for Dec 602 to elicit inflammation in the gut.

Study on Static Characteristics of Aerostatic Bearing Based on Porous SiC Ceramic Membranes.

The porous aerostatic bearing is a new supporting structure that is widely used in precision and ultraprecision engineering and the aerospace and other fields. The aerostatic bearing has a good bearing capacity and static stiffness. In this work, the numerical and experimental research on the static characteristics of an aerostatic bearing based on a porous SiC ceramic membrane is presented. The porous ceramic membrane prepared by reactive sintering, with a porosity of 25.8% and a pore size of 20.55 µm, was used as the restrictor to fabricate the aerostatic bearing. It was found that the ceramics have good permeability, and the permeability coefficient reached 2.78 × 10-13 m2 using permeability-test experiments. The effects of the gas-supply pressure and permeability coefficient on the static characteristics of the aerostatic bearing based on porous ceramics were analyzed using Fluent simulation calculation. When the gas-supply pressure was 0.5 MPa and the gas-film thickness was 6 µm, the static stiffness of the aerostatic bearing reached a maximum of 20.9 N/µm, while the bearing capacity was 632.5 N. The numerical results of the static characteristics of the aerostatic bearing are highly consistent with the experimental results, which verifies the accuracy of the Fluent simulation, and provides convenience for studying the static characteristics of aerostatic bearings.

Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration.

Tumor cell migration is affected by the aryl hydrocarbon receptor (AhR). However, the systematic molecular mechanisms underlying AhR-mediated migration of human neuroblastoma cells are not fully understood. To address this issue, we performed an integrative analysis of mRNA and microRNA (miR) expression profiles in human neuroblastoma SK-N-SH cells treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of AhR. The cell migration was increased in a time- and concentration- dependent manner, and was blocked by AhR antagonist (CH223191). A total of 4,377 genes were differentially expressed after 24-hour-treatment with 10-10 M TCDD, of which the upregulated genes were significantly enriched in cell migration-related biological pathways. Thirty-four upregulated genes, of which 25 were targeted by 78 differentially expressed miRs, in the axon guidance pathway were experimentally confirmed, and the putative dioxin-responsive elements were present in the promoter regions of most genes (79 %) and miRs (82 %) in this pathway. Furthermore, two promigratory genes (CFL2 and NRP1) induced by TCDD was reversed by blockade of AhR. In conclusion, AhR-mediated mRNA-miR networks in the axon guidance pathway may represent a potential molecular mechanism of dioxin-induced directional migration of human neuroblastoma cells.

Cerebrospinal fluid exosomal miR-152-3p predicts the occurrence of subarachnoid haemorrhage and regulates vascular smooth muscle cell dysfunction.

INTRODUCTION: Ruptured intracranial aneurysm (RA) can lead to subarachnoid haemorrhage (SAH). This study was to explore the predictive value of cerebrospinal fluid (CSF) derived exosome miR-152-3p and its regulatory role in the human vascular smooth muscle cells (HVSMCs). MATERIAL AND METHODS: Real-time quantitative polymerase reaction was carried out to detect CSF exosome miR-152-3p in 66 patients with unruptured intracranial aneurysms (UA), 69 patients with RA, and 68 patients with hydrocephalus. Clinical predictive value of SAH occurrence was assessed using receiver operating characteristic curve (ROC) and logistics regression analysis. Cell Counting Kit-8 and Transwell were employed to detect the proliferation and migration of HVSMCs. The binding relationship between miR-152-3p and PTEN was confirmed by the dual-luciferase reporter assay. RESULTS: Compared with hydrocephalus, exosome miR-152-3p was lower in patients with intracranial aneurysms, and among them, RA was lower than in patients with UA (p < 0.001). ROC confirmed that exosome miR-152-3p not only distinguishes patients with UA from patients with hydrocephalus but also predicts SAH in patients with intracranial aneurysms. Logistic regression analysis showed that miR-152-3p (OR = 0.039, 95% CI = 0.015-0.106, p < 0.001) and aneurysm size (OR = 2.701, 95% CI = 1.045-6.890, p = 0.040) were independent predictors of progression for UA to RA. Increased miR-152-3p inhibited the proliferation and migration of HVSMCs. PTEN was the direct target gene of miR-152-3p, which was elevated in CSF-derived exosomes and negatively correlated with miR-152-3p levels. CONCLUSIONS: Our study confirmed that the CSF-derived exosome miR-152-3p was a feasible predictor of SAH and was involved in the dysfunction of HVSMCs.