Abstract
To provide a theoretical basis for the prevention and treatment of atherosclerosis (As), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on ...inducing the lipid deposition and foam cell formation of the vascular smooth muscle cell (VSMC) via C1q/Tumor necrosis factor-related protein9 (CTRP9) promoter region Hypermethylation negative regulating endoplasmic reticulum stress (ERs). Therefore, apolipoprotein E deficient (ApoE
−/−
) mice were randomly divided into the control ApoE
−/−
+ normal diet (NC) and high methionine ApoE
−/−
+ (normal diet supplemented with 1.7% methionine (HMD) groups (n = 6 mice/group). Following feeding for 15 weeks, the serum levels of Homocysteine (Hcy), total cholesterol (TC), and triglyceride (TG) were measured using an automatic biochemical analyzer. HE and oil red O staining were performed on the aorta roots to observe the pathological changes. Additionally, immunofluorescence staining was performed to detect the protein expression levels of CTRP9, glucose-regulated protein 78 kD (GRP78), phosphorylated protein kinase RNA-like ER kinase (p-PERK), activating transcription factor 6a (ATF6a), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), sterol regulatory element binding proteins-1c (SREBP1c) and sterol regulatory element binding proteins-2 (SREBP2) in VSMC derived from murine aortic roots. In vitro, VSMC was stimulated with 100 μmol/l Hcy. After transfection of plasmids with overexpression and interference of CTRP9, ERs agonist (TM) and inhibitor (4-PBA) were given to stimulate VSMC cells. HE staining and oil red O staining were used to observe the effect of Hcy stimulation on lipid deposition in VSMC. Additionally, The mRNA and protein expression levels of CTRP9, GRP78, PERK, ATF6a, IRE1α, SREBP1c, and SREBP2 in VSMC were detected by RT-qPCR and western blot analysis, respectively. Finally, The methylation modification of the CTRP9 promoter region has been studied. The NCBI database was used to search the promoter region of the CTRP9 gene, and CpG Island was used to predict the methylation site. After Hcy stimulation of VSMC, overexpression of DNMT1, and intervention with 5-Azc, assess the methylation level of the CTRP9 promoter through bisulfite sequencing PCR (BSP). The results showed that the serum levels of Hcy, TC, and TG in the ApoE
−/−
+ HMD group were significantly increased compared with the ApoE
−/−
+ NC group. In addition, HE staining and oil red O staining showed obvious AS plaque formation in the vessel wall, and a large amount of fat deposition in VSMC, thus indicating that the hyperhomocysteinemia As an animal model was successfully established. Furthermore, CTRP9 were downregulated, while GRP78, p-PERK, ATF6a, p-IRE1α, SREBP1c, SREBP2 was upregulated in aortic VSMC in the ApoE
−/−
+ HMD group. Consistent with the in vivo results, Hcy can inhibit the expression of CTRP9 in VSMC and induce ERs and lipid deposition in VSMC. Meanwhile, the increased expression of CTRP9 can reduce ERs and protect the lipid deposition in Hcy induced VSMC. Furthermore, ERs can promote Hcy induced VSMC lipid deposition, inhibition of ERs can reduce Hcy induced VSMC lipid deposition, and CTRP9 may play a protective role in Hcy induced VSMC lipid deposition and foam cell transformation through negative regulation of ERs. In addition, The CTRP9 promoter in the Hcy group showed hypermethylation. At the same time as Hcy intervention, overexpression of DNMT1 increases the methylation level of the CTRP9 promoter, while 5-Azc can reduce the methylation level of the CTRP9 promoter. Finally, Hcy can up-regulate the expression of DNMT1 and down-regulate the expression of CTRP9. After overexpression of DNMT1, the expression of CTRP9 is further decreased. After 5-Azc inhibition of DNMT1, the expression of DNMT1 decreases, while the expression of CTRP9 increases. It is suggested that the molecular mechanism of Hcy inhibiting the expression of CTRP9 is related to the hypermethylation of the CTRP9 promoter induced by Hcy and regulated by DNMT1. 5-Azc can inhibit the expression of DNMT1 and reverse the regulatory effect of DNMT1 on CTRP9. Overall, the results of the present study suggested that Hcy induces DNA hypermethylation in the CTRP9 promoter region by up-regulating DNMT1 expression, and negatively regulates ERs mediated VSMC lipid deposition and foam cell formation. CTRP9 may potentially be a therapeutic target in the treatment of hyperhomocysteinemia and As.
The high sensitivity flexible capacitive pressure sensor (FCPS) manufactured in a fast and efficient way has friendly man-machine interaction function. In this paper, a high-sensitivity FCPS is ...developed by using a two-step template method to reproduce biomimetic microtower polydimethylsiloxane (PDMS) from the lotus leaf surface. The capacitive sensor is composed of a PDMS dielectric layer and the Cu nanowire electrodes sandwiching in the middle, with a high sensitivity of ~1.207 kPa−1, a low detection limit of less than 0.02 kPa and a fast response time of 61.6 ms. Particularly, the sensing performance can be kept basically unchanged when bent at a 5 mm radius. Moreover, the FCPS can withstand 4000 repeated tests and maintain stable performance, and the sensitivity is almost the same in the process of loading and unloading, suggesting the high robustness. These results demonstrates the FCPSs have potential applications in electronic wearables, human health monitoring and uneven surface applications.
Display omitted
•A high-sensitivity FCPS is developed by using a two-step template method to reproduce biomimetic microtower structure.•The flexible capacitive sensor has a high sensitivity of ~1.207 kPa-1 and a fast response time of 61.6 ms.•Particularly, the sensing performance can be kept basically unchanged when bent at a 5 mm radius.
To provide a theoretical basis for the prevention and treatment of atherosclerosis (AS), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on regulating ...the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) via sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) through Nedd4-like E3 ubiquitin-protein ligase WWP2 (WWP2). Here, Based on the establishment of ApoE-/- mouse models of high Hcy As and the model of Hcy stimulation of VSMC in vitro to observe the interaction between WWP2 and STAT3 and its effect on the proliferation, migration, and phenotypic transformation of Hcy-induced VSMC, which has not been previously reported. This study revealed that WWP2 could promote the proliferation, migration, and phenotype switch of Hcy-induced VSMC by up-regulating the phosphorylation of SIRT1/STAT3 signaling. Furthermore, Hcy might up-regulate WWP2 expression by inhibiting histone H3K27me3 expression through up-regulated UTX. These data suggest that WWP2 is a novel and important regulator of Hcy-induced VSMC proliferation, migration, and phenotypic transformation.
As we know, valley-Hall kink states or pseudospin helical edge states are excited by polarized-momentum-locking left-handed circular polarization (LCP) and right-handed circular polarization (RCP) ...because the valley-Hall kink modes or pseudospin polarized modes have intrinsic and local chirality, which is difficult for these states to achieve phase modulation. Here we theoretically design and study a compatible topological photonic system with coexistence of photonic quantum Hall phase and pseudospin Hall phase, which is composed of gyromagnetic photonic crystals with a deformed honeycomb lattice containing six cylinders. A typical kind of hybrid topological waveguide states with pseudospin-characteristic, magnetic field-dependent, and strong robustness against backscattering and perfect electric conductor (PEC) is realized in the present system. Furthermore, we re-design a structure with intersection-liked, achieve splitting for one-way pseudospin quantum Hall edge states by using phase modulation. Robustness of the one-way pseudospin-quantum Hall edge states in splitting has been demonstrated as well. Additionally, PEC inserted in transport channel brings optical path difference in waveguide transmission, which would influence splitting for hybrid topological waveguide states in phase difference modulation. This work not only provides a new way for manipulation (i.e., phase modulation) of hybrid topological waveguide states in compatible topological photonic system from distinct topological classes but also has potential in various applications, such as sensing, signal processing, and on-chip communications.
Dolomite reactivity with wet and dry supercritical CO2 were evaluated. Dolomite does not react with dry CO2. H2O-saturated supercritical CO2 dissolves dolomite and precipitates carbonate mineral. ...Temperature/reaction time control morphology and extent of carbonate mineralization. Reaction with wet CO2 may impact trapping, caprock integrity, and CCS/EOR injectivity.
Carbon dioxide injection in porous reservoirs is the basis for carbon capture and storage, enhanced oil and gas recovery. Injected carbon dioxide is stored at multiple scales in porous media, from the pore-level as a residual phase to large scales as macroscopic accumulations by the injection site, under the caprock and at reservoir internal capillary pressure barriers. These carbon dioxide saturation zones create regions across which the full spectrum of mutual CO2–H2O solubility may occur. Most studies assume that geochemical reaction is restricted to rocks and carbon dioxide-saturated formation waters, but this paradigm ignores injection of anhydrous carbon dioxide against brine and water-alternating-gas flooding for enhanced oil recovery.
A series of laboratory experiments was performed to evaluate the reactivity of the common reservoir mineral dolomite with water-saturated supercritical carbon dioxide. Experiments were conducted at reservoir conditions (55 and 110°C, 25MPa) and elevated temperature (220°C, 25MPa) for approximately 96 and 164h (4 and 7days). Dolomite dissolves and new carbonate mineral precipitates by reaction with water-saturated supercritical carbon dioxide. Dolomite does not react with anhydrous supercritical carbon dioxide. Temperature and reaction time control the composition, morphology, and extent of formation of new carbonate minerals.
Mineral dissolution and re-precipitation due to reaction with water-saturated carbon dioxide may affect the contact line between phases, the carbon dioxide contact angle, and the relative permeability and permeability distribution of the reservoir. These changes influence fundamental properties of hysteresis of drainage and imbibition cycles, rock wettability, and capillary pressure. The efficacy of physical carbon dioxide trapping mechanisms, integrity of caprock, and injectivity of a carbon dioxide storage reservoir as well as the injectivity and production rate of an enhanced oil recovery operation may be affected.
SAGD (Steam Assisted Gravity Drainage) is used in Canadian fields where there are interlayers that impede steam chamber development and thus impede production. Many experiments have been conducted on ...the effect of interlayers on oil recovery. However, the swelling characteristics of interlayers under different conditions, as well as the possible clay mineral transformation and particle migration of clay particles at high temperatures, are rarely studied. In this paper, the swelling characteristics of natural oil sands and artificial clay samples were studied by high temperature hydration swelling experiments to obtain a better comparison. The effects of temperature, pressure and solution type on the swelling rate of oil sand were studied. The uniaxial compressive strength of the core in the presence of clay was studied by the scribe test. In addition, before and after the aging test at 220 °C and 2.5 MPa, the clay mineral composition was studied by the X-ray diffraction method, and the mineral transformation was proved. Finally, the impact of clay swelling on oil production is investigated by simulating the particle migration effect while considering the swelling effect. The results show that the swelling rate of oil sand increases with the increment of temperature and the decrement of pressure. The swelling rate of an artificial clay sample in distilled water is the highest, while a 1% KCl + 1% CaCl2 solution has the best swelling inhibition effect. This study aims to provide new insights into reservoir damage research during SAGD development.
Previous studies reported that miR-433 exerts function widely in human tumorigenesis and development. Here, we further investigate the potential role of miR-433 in glioma. Quantitative real-time PCR ...demonstrated that miR-433-3p and miR-433-5p were low expressed in glioma tissues and cell lines. Functional studies suggested that the overexpression of miR-433-3p suppressed proliferation, induced apoptosis and inhibited invasion and migration of human glioma cells. But the growth and metastasis of glioma cells were not significantly influenced by overexpression of miR-433-5p. In a xenograft model, we also showed that miR-433-3p had an inhibitory effect on the growth of glioma. Bioinformatics coupled with luciferase and western blot assays revealed that CREB is a direct target of miR-433-3p, and the overexpression of CREB can rescue the phenotype changes induced by miR-433-3p overexpression. Besides, miR-433-3p could increase chemosensitivity of glioma to temozolomide by targeting CREB in vitro and in vivo. Taken together, these results suggest that miR-433-3p may function as a potential marker in diagnostic and therapeutic target for glioma.
Purpose
To compare multiplexed sensitivity-encoding diffusion-weighted magnetic resonance imaging (MUSE-DWI) and conventional DWI (cDWI) techniques in thyroid MRI.
Materials and methods
Nineteen ...patients who underwent thyroid MRI using both MUSE-DWI and cDWI at a 3.0 T MRI system were enrolled. Qualitative parameters (image quality, thyroid contour, and lesion conspicuity) and quantitative parameters (signal-to-noise ratio (SNR), lesion-to-thyroid contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC)) were compared between the two sequences. In addition, ADC values derived from MUSE-DWI and cDWI were separately compared between benign and malignant lesions.
Results
MUSE-DWI outperformed cDWI in terms of image quality, thyroid contour, and lesion conspicuity. Significantly, higher signal-to-noise ratio (SNR) in both the thyroid and its lesion were found in MUSE-DWI than those in cDWI (both
P
< 0.05). The lesion-to-thyroid contrast-to-noise ratio (CNR) values were also significantly higher in MUSE-DWI than those in cDWI (
P
< 0.05). The apparent diffusion coefficient (ADC) of the thyroid in MUSE-DWI was significantly lower than that in cDWI (
P
< 0.05). The ADC of the lesion in MUSE-DWI was also significantly lower than that in cDWI (
P
< 0.05). In addition, ADC values derived from MUSE-DWI and cDWI were significantly higher in benign lesions than malignant lesions (
P
< 0.05).
Conclusion
Compared with cDWI, MUSE-DWI can improve the image quality, thyroid contour sharpness, lesion conspicuity, SNR in both the thyroid and its lesions, and enhancing the CNR between lesions and thyroid.
Hydrogen sulfide (H(2)S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H(2)S protects human ...skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl(2)), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H(2)S) for 30 min before exposure to CoCl(2) for 24 h significantly attenuated CoCl(2)-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl(2)-induced COX-2 overexpression and PGE(2) secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H(2)S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl(2)-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl(2). Notably, NAC, a ROS scavenger, conferred a similar protective effect of H(2)S against CoCl(2)-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H(2)S protects HaCaT cells against CoCl(2)-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway.
The construction defects in grouting sleeves can jeopardize the safety of precast reinforced concrete structures. Thus, efficient and accurate defect detection is critical in engineering ...construction. In this paper, a defect detection method based on piezoelectric wave theory was proposed. Two piezoelectric ceramics were arranged within the grouting sleeve. One piezoelectric ceramic was affixed on the top of the steel bar, while the other was embedded in the grouting material, serving as the driver and sensor, respectively. The compactness defects, air cavity defects, steel anchoring defects, and water–binder ratio defects were set in the grouting sleeves, and the trends in time domain signals and signal evaluation indicators based on the wavelet packet total energy value (WPTEV) of different specimens were investigated. Based on the WPTEV, the evaluation index (EI) was proposed. In addition, the effect of the grouting material’s age on the piezoelectric wave signal was verified. Furthermore, the influence of grouting material defects on signals was simulated in ABAQUS, and the time domain signals and wavelet packet energy of sensor signals for specimens with varying defect dimensions were evaluated. The results showed that: (1) The defects in the grouting materials reduced the stress waves propagated through the grouting materials, resulting in a decrease in attenuation and an increasing trend in the signal; (2) The peak-to-peak values of piezoelectric ceramic sensors and the WPTEV of the signal increased with the degree of defects, and the WPTEV was more pronounced. For specimen M68, the WPTEV was 3.3 times that of the healthy specimen, however, the peak-to-peak value was only 2.3 times that of the healthy specimen; (3) The degree of defects was accurately determined by the defect evaluation index (EI) based on the WPTEV; (4) The signal was significantly attenuated with the increase in the age of the grouting material, especially in the first three days, and finally the signal achieved a stable value; (5) The numerical simulation indicated that the defects in the length and thickness of the air cavity in the grouting material were efficiently detected by the proposed piezoelectric arrangement in this study.