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We aimed to explore the effect of dibazol on the ophthalmic artery (OA) and ophthalmic artery smooth muscle cells (OASMCs) of C57BL/6J mice as well as the underlying mechanisms. The OA of C57BL/6J mice was isolated under a dissecting microscope for primary OASMCs culture and myogenic tests. OASMCs were identified through morphological and immunofluorescence analyses. Morphology changes in the OASMCs were examined by staining using rhodamine-phalloidin. We performed a collagen gel contraction assay to measure the contractile and relaxant activities of the OASMCs. The molecular probe Fluo-4 AM was used to examine intracellular free Ca2+ levels ([Ca2+]in). The myogenic effects of OA were examined using wire myography. Additionally, the whole-cell patch-clamp technique was used to investigate the mechanisms underlying the relaxant effect of dibazol on L-type voltage-gated Ca2+ channels (LVGC) in isolated cells. 10-5 M dibazol significantly inhibited the contraction of OASMCs and increased the [Ca2+]in response to 30 mM KCl in a concentration-dependent manner. Dizabol had a more significant relaxant effect than 10-5 M isosorbide dinitrate (ISDN). Similarly, dibazol showed a significant dose-dependent relaxant effect on OA contraction induced by 60 mM KCl or 0.3 µM 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619). The current-voltage (I-V) curve revealed that dibazol decreased Ca2+ currents in a concentration-dependent manner. In conclusion, dibazol exerted relaxant effects on the OA and OASMCs, which may involve the inhibition of the Ca2+ influx through LVGC in the cells.
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Arteria Oftálmica , Vasodilatación , Ratones , Animales , Vasodilatación/fisiología , Ratones Endogámicos C57BL , Contracción Muscular/fisiología , CalcioRESUMEN
The excellent biocompatibility of calcium phosphate (CaP) coatings makes them widely used in magnesium (Mg) alloy orthopedic implant materials. However, the porous morphology of CaP coatings limits their corrosion resistance. A cupric oxide (CuO) doped titania (TiO2) sol-gel coating is prepared on a porous hydroxyapatite (HA) coating. According to electrochemical test results, the HA/CuO-TiO2 coating obtains a current density of 6 × 10-4 mA/cm2, lower than that of the Mg alloy (2.6 × 10-2 mA/cm2). The hydrogen evaluation of the HA/CuO-TiO2 coating is only 1/12 that of the Mg alloy after immersion for 7 days. In addition, the HA/CuO-TiO2 coating has an antibacterial rate of 99.5 ± 0.4% against Staphylococcus aureus, significantly higher than that of the HA coating (19.8 ± 0.3%) and HTC0 coating (38.4 ± 0.5%). The CuO doped composite coating has no adverse effect or cytotoxicity on cell proliferation (cell viability ≥79.6%). Hence, the HA/CuO-TiO2 composite coating is useful for enhancing the corrosion resistance and antibacterial properties of Mg alloys while ensuring cytocompatibility. The HA/CuO-TiO2 coated AZ60 Mg alloy can meet the requirements of clinical application.
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Aleaciones , Magnesio , Aleaciones/toxicidad , Antibacterianos/toxicidad , Materiales Biocompatibles Revestidos/toxicidad , Cobre , Corrosión , Durapatita , Propiedades de Superficie , TitanioRESUMEN
As potential degradable biomaterials, magnesium (Mg) alloys have development prospects in the field of orthopedic load-bearing, whereas the clinical application has encountered a bottleneck due to a series of problems caused by its rapid corrosion. In this study, strontium-substituted calcium phosphate (CaP) coatings with different structures were prepared on the surface of the Mg matrix by a simple one-step electrodeposition method at different temperatures, which enhanced the poor corrosion resistance of the Mg matrix. The coated sample prepared at 65 °C reduced the corrosion current density by 3 orders of magnitude and increased the impedance by nearly 2 orders of magnitude compared with bare Mg alloy, thanks to its dense fibrous structure similar to that of natural bones. Although the coating composition varies with different preparation temperatures, CaP, as an inorganic component similar to natural bone, has good cytocompatibility. Doping the right amount of strontium, which is a trace element in human bones, is beneficial to stimulate osteoblast differentiation, inhibit the activity of osteoclasts, and induce the formation of bone tissues. This provides a new option for modifying the Mg alloy with CaP coatings as a base.
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Calcio , Magnesio , Humanos , Calcio/química , Magnesio/farmacología , Magnesio/química , Corrosión , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química , Temperatura , Galvanoplastia , Aleaciones/farmacología , Aleaciones/química , Estroncio/farmacología , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/químicaRESUMEN
Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity. Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve. Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628). Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.
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Biomarcadores , Hipertensión Pulmonar , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Fumar , Humanos , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores/sangre , Fumar/efectos adversos , Fumar/sangre , Fumar/epidemiología , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Anciano , Factores de Riesgo , Medición de Riesgo , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , China/epidemiología , Adulto , Presión ArterialRESUMEN
Flexible quantum spin electronic devices based on ferromagnetic insulators have attracted wide attention due to their outstanding advantages of low-power dissipation and noncontact sensing. However, ferromagnetic insulators, such as monocrystalline yttrium iron garnet (Y3Fe5O12, YIG), hve weak stress effects with a small magnetostrictive coefficient (λ110, 10 ppm), making it difficult to achieve a large magnetic tunable amplitude. In this paper, large-scale (with a diameter of 40 mm), flexible Pt/YIG heterojunctions were obtained by double-cavity magnetron sputtering technology, indicating typical soft magnetism and good bending fatigue characteristics. Here, the 3 nm thickness of the Pt layer triggers an obvious magnetic proximity effect, in which the in-plane ferromagnetic resonance field is decreased by 70 Oe compared to flexible Cu/YIG heterojunctions. Meanwhile, it shows a wide tunable amplitude of 110 Oe under the flexible bending stresses, which is induced by the sensitive interface effect of Pt (3 nm)/YIG heterojunctions. The saturation magnetization of Pt/YIG heterojunctions is negatively correlated with Pt thickness rather than the relative stability of Cu/YIG heterojunctions, depending on the magnetic proximity effect. It brings greater application possibilities for flexible stress-sensitive magnetic oxides in spin logic electronic devices.
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The ultrahigh flexibility and elasticity achieved in freestanding single-crystalline ferroelectric oxide membranes have attracted much attention recently. However, for antiferroelectric oxides, the flexibility limit and fundamental mechanism in their freestanding membranes are still not explored clearly. Here, we successfully fabricate freestanding single-crystalline PbZrO3 membranes by a water-soluble sacrificial layer technique. They exhibit good antiferroelectricity and have a commensurate/incommensurate modulated microstructure. Moreover, they also have good shape recoverability when bending with a small radius of curvature (about 2.4 µm for the thickness of 120 nm), corresponding to a bending strain of 2.5%. They could tolerate a maximum bending strain as large as 3.5%, far beyond their bulk counterpart. Our atomistic simulations reveal that this remarkable flexibility originates from the antiferroelectric-ferroelectric phase transition with the aid of polarization rotation. This study not only suggests the mechanism of antiferroelectric oxides to achieve high flexibility but also paves the way for potential applications in flexible electronics.
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Liquid-solid contact electrification (CE) is essential to diverse applications. Exploiting its full implementation requires an in-depth understanding and fine-grained control of charge carriers (electrons and/or ions) during CE. Here, we decouple the electrons and ions during liquid-solid CE by designing binary superhydrophobic surfaces that eliminate liquid and ion residues on the surfaces and simultaneously enable us to regulate surface properties, namely work function, to control electron transfers. We find the existence of a linear relationship between the work function of superhydrophobic surfaces and the as-generated charges in liquids, implying that liquid-solid CE arises from electron transfer due to the work function difference between two contacting surfaces. We also rule out the possibility of ion transfer during CE occurring on superhydrophobic surfaces by proving the absence of ions on superhydrophobic surfaces after contact with ion-enriched acidic, alkaline, and salt liquids. Our findings stand in contrast to existing liquid-solid CE studies, and the new insights learned offer the potential to explore more applications.
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Magnesium (Mg) alloys, a degradable material, have been studied for medical applications due to their excellent mechanical and chemical properties. However, their applications are limited by rapid corrosion. In this work, stearic acid and sodium stearate were used to treat the silane-induced calcium phosphate dihydrate coating to improve its protection for the Mg alloy further without changing the bone-like structure of calcium phosphate. The different effects of stearic acid treatment and sodium stearate treatment were compared. Electrochemical test and immersion test results confirmed that the corrosion resistance of the stearic acid-treated composite coating was greatly enhanced with a reduced corrosion current density by 3 orders of magnitude and hydrogen evolution reduced to 1/25 after 14 days. The stearic acid-treated coating also exhibited improved in vitro biocompatibility corroborated by promoted cell viability and better cell morphology.
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Aleaciones , Magnesio , Magnesio/farmacología , Magnesio/química , Aleaciones/farmacología , Aleaciones/química , Corrosión , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química , Biomimética , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/químicaRESUMEN
Voltage control of magnetic anisotropy (VCMA) in Si-compatible ferroelectric/ferromagnetic multiferroic thin films is promising to enable power-efficient and integrated magnetic memories. However, their VCMA effect is weak and is always smaller than that of the bulk counterparts. Here, we achieve a more substantial VCMA effect in thin films than in the bulk, benefiting from the large in-plane piezo-strain mediated magnetoelectric coupling under strong fields. Si-compatible ferroelectric Pb(Zr,Ti)O3 (PZT) thin films with large breakdown strength of up to 3.2 MV cm-1 are fabricated to further construct multiferroic thin films. Since conventional methods fail to measure the VCMA effect under strong fields, we establish a micro-ferromagnetic resonance method based on micro-fabrication. An enhanced VCMA effect is demonstrated in PZT/CoFeB thin films, whose voltage-induced effective magnetic field (Heff) could experimentally reach 26.1 Oe, which is much stronger than that in bulk control samples "PZT ceramic/CoFeB" (2.6 Oe) and "PMN-PT single crystal/CoFeB" (18.5 Oe) as well as previous reports. Theoretically, the Heff in thin films could be > 60 Oe near the breakdown strength, resulting from a giant in-plane piezo-strain S31 < -0.3%, which is comparable to that of the best ferroelectric single crystals. Si-compatible multiferroic thin films with enhanced VCMA will be a useful platform for developing integrated magnetic and spintronic devices.
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Surface bacterial fouling has become an urgent global challenge that calls for resilient solutions. Despite the effectiveness in combating bacterial invasion, antibiotics are susceptible to causing microbial antibiotic resistance that threatens human health and compromises the medication efficacy. In nature, many organisms have evolved a myriad of surfaces with specific physicochemical properties to combat bacteria in diverse environments, providing important inspirations for implementing bioinspired approaches. This review highlights representative natural antibacterial surfaces and discusses their corresponding mechanisms, including repelling adherent bacteria through tailoring surface wettability and mechanically killing bacteria via engineering surface textures. Following this, we present the recent progress in bioinspired active and passive antibacterial strategies. Finally, the biomedical applications and the prospects of these antibacterial surfaces are discussed.
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Magnesium (Mg) and its alloys have exhibited great potential for orthopedic applications; however, their poor corrosion resistance and potential cytotoxicity have hindered their further clinical applications. In this study, we prepared a calcium phosphate (Ca-P) coating with a micro-nanofibrous porous structure on the Mg alloy surface by a chemical conversion method. The morphology, composition, and corrosion performance of the coatings were investigated by scanning electron microscope (SEM), energy-dispersive spectrometer (EDS), X-ray diffraction (XRD), immersion tests, and electrochemical measurements. The effects of the preparation temperature of the Ca-P coatings were analyzed, and the results confirmed that the coating obtained at 60 °C had the densest structure and the best corrosion resistance. In addition, a systematic investigation into cell viability, ALP activity, and cell morphology confirmed that the Ca-P coating had excellent biocompatibility, which could effectively promote the proliferation, differentiation, and adhesion of osteoblasts. Hence, the Ca-P coating demonstrates great potential in the field of biodegradable Mg-based orthopedic implant materials.
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Aleaciones , Nanofibras , Aleaciones/química , Fosfatos de Calcio/química , Materiales Biocompatibles Revestidos/química , Corrosión , Magnesio/farmacología , PorosidadRESUMEN
Magnesium (Mg)-based composites, as biomaterials, have attracted widespread attention due to their adjustable mechanical properties like elastic modulus, ductility, ultimate tensile strength, and corrosion resistance. In this study, hydroxyapatite (HA) reinforced ZK61 Mg-matrix composites were prepared by powder metallurgy and hot extrusion methods. The influence of the content of HA (10 wt%, 20 wt%, and 30 wt%) on the microstructure, density, mechanical properties, corrosion property and biocompatibility were investigated. The results showed that the density and yield strength of the composites match those of natural bone. Moreover, the composite with 10 % HA (ZK61-10HA) exhibited the best corrosion resistance, as determined by the electrochemical measurement and immersion test in simulated body fluid (SBF) at 37 °C. In addition, the ZK61-10HA composite significantly enhanced the cell viability (≥78 %) compared with ZK61 alloy in vitro testing. It is demonstrated that the mechanical properties, corrosion resistance and biocompatibility of Mg alloy can be effectively controlled by adjusting the content of HA, which suggested that the ZK61-HA composites were promising candidates for degradable implant materials.
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Durapatita , Magnesio , Aleaciones , Materiales Biocompatibles/farmacología , Corrosión , Ensayo de MaterialesRESUMEN
This study is designed to investigate the role of novel protein kinases C (nPKC) in mediating pulmonary artery smooth muscle cells (PASMCs) proliferation in pulmonary hypertension (PH) and the underlying mechanisms. Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCdelta (PKCδ) and PKCepsilon (PKCε) and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.
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Hipoxia de la Célula/fisiología , Hipertensión Pulmonar/patología , Miocitos del Músculo Liso , Proteína Quinasa C/biosíntesis , Arteria Pulmonar/patología , Animales , Proliferación Celular , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Oncogénica v-akt/efectos de los fármacos , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C-delta/efectos de los fármacos , Proteína Quinasa C-epsilon/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Regulación hacia Arriba/fisiologíaRESUMEN
Magnesium (Mg) and its alloys exhibit great potential in clinical applications owing to the outstanding biological performance and excellent mechanical properties, whereas the quick corrosion rate in the physiological environment has limited their further clinical application. In this work, we designed and developed a multifunctional polypyrrole/zinc oxide (Ppy/ZnO) composite coating by cyclic voltammetry method, aiming to enhance the biocorrosion resistance, biocompatibility and antibacterial property of the Mg alloys. The electrochemical and immersion tests indicated that the corrosion resistance of the Mg alloy was improved significantly by the composite coating. A systematic in vitro investigation of cellular response confirmed that the composite coating significantly promoted the adhesion and proliferation of cells. In addition, the composite coating showed a remarkable antibacterial ability of 96.5⯱â¯2.6 % against Escherichia coli (E.coli). The enhanced corrosion resistance, cytocompatibility, and antibacterial property of the Ppy/ZnO coated Mg alloy makes it a promising candidate as orthopedic implants material.
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Aleaciones , Óxido de Zinc , Materiales Biocompatibles Revestidos/farmacología , Corrosión , Magnesio , Ensayo de Materiales , Polímeros , PirrolesRESUMEN
To validate its efficacy in the context of the human immune system, a novel therapeutic vaccine of hGM-CSF/hTNFα surface-modified PC-3 cells against human prostate cancer was evaluated in the human peripheral blood lymphocytes-severe combined immunodeficiency (huPBL-SCID) chimeric mouse model. The hGM-CSF or/and hTNFα modified vaccines inhibited prostate cancer growth effectively so as to prolong the mouse survival significantly. The splenocytes from the hGM-CSF/hTNFα vaccine-inoculated mice showed the strongest tumor-specific cytotoxicity against PC-3 cells and the highest production of IFNɤ. These features indicated that type 1 protective immune response was induced efficiently against human prostate cancer and further enhanced through synergetic adjuvant effects of hGM-CSF and hTNFα.