A facile synthetic route for TiO2-CdSe heterostructures was proposed based on dentate binding of TiO2 to carboxyl. Carboxyl functionalized CdSe quantum dots (CF-CdSe QDs) were successfully bonded onto TiO2 nanoparticles (NPs), which could significantly improve the photoelectrochemical (PEC) properties of TiO2 NPs. This is ascribed to the fact that CdSe QDs with a narrow band gap could be stimulated under visible light irradiation, and the energy levels of TiO2 NPs and CF-CdSe QDs are aligned with an electrolyte solution. High resolution transmission electron microscopy images revealed the heterostructures of the TiO2-CdSe composites. Ultraviolet visible spectroscopy, photoluminescence emission spectroscopy and electrochemical impedance spectroscopy analysis exhibited that the prepared TiO2-CdSe heterostructures have improved light absorption, charge separation efficiency and electron transfer ability in the visible light region. TiO2-CdSe heterostructures were used as versatile labels for fabrication of PEC and electrochemical immunosensors, and human immune globulin G (HIgG) was used as a model analyte. The immunosensor showed high sensitivity, a low detection limit and a wide linear range, which could be applied in practical serum sample analysis. The constructed TiO2-CdSe heterostructures would have potential applications in photocatalysis, aptasensors, cytosensors and other areas of nanotechnology.
A new type of all-solid-state polymeric membrane ion-selective electrodes (ISEs) is developed by using a nanoporous gold (NPG) film as solid contact. The NPG film is in situ formed on the surface of a gold wire electrode by the multicyclic electrochemical alloying/dealloying method. The characteristics of the NPG film, such as the large surface area, high double layer capacitance, and good conductivity, have been demonstrated by cyclic voltammetry and electrochemical impedance spectroscopy. The NPG film offers a well-defined interface between the electronic conductor and the ion-selective membrane. The NPG film-based all-solid-state K(+) ISE shows a stable Nernstian response within the concentration range from 10(-6) to 10(-2) M, and the detection limit is 4.0 × 10(-7) M. The proposed electrode exhibits an improved potential stability with a reduced water layer in comparison with the coated-wire K(+)-ISE, which is due to the bicontinuous electron- and ion-conducting properties of the ionophore-doped polymeric membrane/NPG film interlayer. Unlike the additionally coated intermediate layers as single-use solid contacts, the in situ formed NPG film as solid contact is reusable. This work provides a versatile method for fabricating the robust, reliable, and low-maintenance miniaturized ISEs.
Pressure overload-induced cardiac interstitial fibrosis is viewed as a major cause of heart failure in patients with hypertension or aorta atherosclerosis. The purpose of this study was to investigate the effects and the underlying mechanisms of genistein (Gen), a natural phytoestrogen found in soy bean extract, on pressure overload-induced cardiac fibrosis.
We investigated whether the anti-atherosclerosis of adiponectin (APN) relates to the reduction of oxidative stress. We observed the overexpression of adiponectin gene with different titers on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE-/-) mice.
This present study investigated the potential of adeno-associated virus serotype 2 (AAV2) mediated BMP-7 (AAV2-BMP-7) to induce odontoblastic differentiation of human dental pulp cells (DPCs) in vitro. AAV2-BMP-7 was constructed to overexpress BMP-7, and the biologic effects of BMP-7 on DPCs were investigated by the evaluation of the activity of alkaline phosphatase (ALPase), the detection of the expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN) expression and the analysis of the proliferative ability of the cells. DPCs that were infected with AAV2-BMP-7 displayed significantly upregulated ALP activity and formed mineralized nodules. Moreover, AAV2-BMP-7 promoted the expression of mineralization-related genes, which included DSPP and OCN. In addition, there was no significant difference between the proliferative ability of AAV2-BMP-7 and the control group. In conclusion, AAV2-BMP-7 promoted the odontoblastic differentiation in DPCs, a clear indication of the therapeutic potential of AAV2-BMP-7 in dental tissue regeneration.
Organic nanoparticles (NPs) with aggregation-induced emission (AIE) have been successfully used for tracking bone marrow stromal cells (BMSCs) in rats with ischemic stroke, highlighting the great potential of such fluorescent NPs in understanding the fate of transplanted stem cells for cell-based therapies.
Insecticide synergists biochemically inhibit insect metabolic enzyme activity and are used both to increase the effectiveness of insecticides and as a diagnostic tool for resistance mechanisms. Considerable attention has been focused on identifying new synergists from phytochemicals with recognized biological activities, specifically enzyme inhibition. Jack pine (Pinus banksiana Lamb.), black spruce (Picea mariana (Mill.) BSP.), balsam fir (Abies balsamea (L.) Mill.), and tamarack larch (Larix laricina (Du Roi) Koch) have been used by native Canadians as traditional medicine, specifically for the anti-inflammatory and antioxidant properties based on enzyme inhibitory activity. To identify the potential allelochemicals with synergistic activity, ethanol crude extracts and methanol/water fractions were separated by Sephadex LH-20 chromatographic column and tested for in vitro glutathione S-transferase (GST) inhibition activity using insecticide-resistant Colorado potato beetle, Leptinotarsa decemlineata (Say) midgut and fat-body homogenate. The fractions showing similar activity were combined and analyzed by ultra pressure liquid chromatography-mass spectrometry. A lignan, (+)-lariciresinol 9'-p-coumarate, was identified from P. mariana cone extracts, and L. laricina and A. balsamea bark extracts. A flavonoid, taxifolin, was identified from P. mariana and P. banksiana cone extracts and L. laricina bark extracts. Both compounds inhibit GST activity with taxifolin showing greater activity compared to (+)-lariciresinol 9'-p-coumarate and the standard GST inhibitor, diethyl maleate. The results suggested that these compounds can be considered as potential new insecticide synergists.
Exposure to pathogens in recreational or drinking water is a serious public health concern. It is important to rapidly determine and identify trace levels of pathogens in real environmental samples. We report here on a label-free potentiometric aptasensor for rapid, sensitive, and selective detection of Listeria monocytogenes (LM), a pathogen widely distributed in the environment. An aptamer binds specifically to internalin A, a surface protein present in LM cells. The target-binding event prevents the aptamer from electrostatically interacting with protamine, which can be sensitively detected using a polycation-sensitive membrane electrode. Using this method, LM can be detected down to 10 CFU mL(-1). Coupled to an online filtration system, the bioassay has been evaluated with spiked coastal seawater samples and shows good recovery and high accuracy. This work demonstrates the possibility of developing potentiometric aptasensors for determination and identification of various bacteria in environmental samples.
RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg(2+)-dependent DNA helicase activity with a 3'?5' polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3'-overhang but is inactive on blunt-ended dsDNA and 5'-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5'-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.
Few studies have evaluated age-related predictors associated with the underuse of medications in patients with coronary heart disease (CHD). The objective of this study was to identify age-related differences in the factors associated with the underuse of recommended medications in patients diagnosed with acute coronary syndrome (ACS).
The aim of the present study was to research the role of nitric oxide (NO) as a mediator of alpha (?)-asarone effect at the pentylenetetrazol (PTZ)-induced epileptiform discharge in rat. ?-Asarone that was injected intraperitoneally twenty minutes before PTZ injection suppressed the clonic discharge effectively and the significant actions lasted for 30 min with no change of clonic amplitude. Administration of ?-asarone did not influence interictal discharge. Four kinds of NO regulators were administered, including non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG) and NO substrate, L-arginine (ARG) and their influence on the actions of ?-asarone were studied, and all of the regulators were administered fifteen minutes before ?-asarone injection. L-NAME and 7-NI reversed the anticlonic activity of ?-asarone, and a significant increase of clonic activity was induced by L-NAME later in L-NAME +.?-asarone + PTZ group. There were no significant differences between AG + ?-asarone + PTZ and ?-asarone + PTZ group. L-ARG played a dual role in this study. It aggravated clonic discharge in the early stage but relieved interictal discharge in the late stage compared with PTZ group alone, and the beneficial effect of ?-asarone was also reversed. All the above results suggest that nNOS/NO pathway mediates the anticonvulsant effect of ?-asarone, and NO played a biphasic role in PTZ modeling process, while iNOS was unrelated to the inhibition effect of ?-asarone on PTZ induced epileptiform activity.
The ?-amyloid (A?) oligomer rather than fibrillar A? has become the important focus of recent studies on the pathogenesis of Alzheimer's disease (AD). Insulin signaling plays important roles in cognitive disease, such as AD. However, in-vivo evidence for the link between central insulin signaling and the A? oligomer are lacking, and the mechanisms underlying the effect of central insulin signaling on AD are still elusive. Our team has established the Presenilin-1 Val97Leu mutant transgenic (PS1V97L) AD mouse model with the intraneuronal A? oligomer as the potential initiator for other pathologies, but without extracellular amyloid plaque formation. Using this model, we investigated the roles of disturbed central insulin signaling induced by intracerebroventricular injection of streptozotocin (STZ) in the progression of AD. We observed that PS1V97L mice after intracerebroventricular injection of STZ showed increased A? oligomer accumulation and aggravated spatial learning and memory deficit in the absence of diabetes symptoms. Furthermore, STZ administration inhibited the activation of the insulin receptor and enhanced the activation of c-Jun NH2-terminal kinase, which was accompanied by increased production of carboxy-terminal fragments from the amyloid precursor protein, in the brain of PS1V97L mice. Overall, our study provided in-vivo evidence for a role of central insulin signaling in AD progression.
The association between the impaired cognitive control and brain regional abnormalities in Internet gaming disorder (IGD) adolescents had been validated in numerous studies. However, few studies focused on the role of the salience network (SN), which regulates dynamic communication among brain core neurocognitive networks to modulate cognitive control. Seventeen IGD adolescents and 17 healthy controls participated in the study. By combining resting-state functional connectivity and diffusion tensor imaging (DTI) tractography methods, we examined the changes of functional and structural connections within SN in IGD adolescents. The color-word Stroop task was employed to assess the impaired cognitive control in IGD adolescents. Correlation analysis was carried out to investigate the relationship between the neuroimaging indices and behavior performance in IGD adolescents. The impaired cognitive control in IGD was validated by more errors during the incongruent condition in color-word Stroop task. The right SN tract showed the decreased fractional anisotropy (FA) in IGD adolescents, though no significant differences of functional connectivity were detected. Moreover, the FA values of the right SN tract were negatively correlated with the errors during the incongruent condition in IGD adolescents. Our results revealed the disturbed structural connectivity within SN in IGD adolescents, which may be related with impaired cognitive control. It is hoped that the brain-behavior relationship from network perspective may enhance the understanding of IGD.
An electrochemical immunosensor for quantitative detection of ?-fetoprotein (AFP) in human serum was developed using graphene sheets (GS) and thionine (TH) as electrode materials and mesoporous silica nanoparticles (MSNs) loaded with ferroferric oxide (Fe3O4) nanoparticles and horseradish peroxidase (HRP) as labels for signal amplification. In this study, the compound of GS and TH (GS-TH) was used as a substrate for promoting electron transfer and immobilization of primary antibody of AFP (Ab1). MSNs were used as a carrier for immobilization of secondary antibody of AFP (Ab2), Fe3O4, and HRP. The synergistic effect occurred between Fe3O4 and HRP and greatly improved the sensitivity of the immunosensor. This method could detect AFP over a wide concentration range from 0.01 to 25ngml(-1) with a detection limit of 4pgml(-1). This strategy may find wide potential application in clinical analysis or detection of other tumor markers.
Room temperature magnetic field effects have not been definitively observed in either single-walled carbon nanotubes (SWCNTs) or C?? under a small magnetic field due to their weak hyperfine interaction and slight difference of g-factor between positive and negative polarons. Here, we demonstrate charge-transfer induced magnetic field effects in nano-carbon C??-SWCNT bulk heterojunctions at room temperature, where the mechanism of magnetic field effects is verified using excited state transition modeling. By controlling SWCNT concentrations and interfacial interactions, nano-carbon heterojunctions exhibit tunability of charge-transfer density and room temperature magnetoconductance of 2.8% under 100?mT external magnetic field. External stimuli, such as electric field and photoexcitation, also play an important role in controlling the magnetic field effects of nano-carbon heterojunctions, which suggests that these findings could enable the control of optoelectronic properties of nano-carbon heterojunctions.
A general label-free photoelectrochemical (PEC) platform was manufactured by assembly of CdSe nanoparticles (NPs) sensitized anatase TiO2-functionalized electrode via layer-by-layer (LBL) strategy. CdSe NPs were assembled on anatase TiO2-functionalized electrode through dentate binding of TiO2 NPs to -COOH groups. Ascorbic acid (AA) was used as an efficient electron donor for scavenging photogenerated holes under visible-light irradiation. The photocurrent response of the CdSe NPs modified electrode was significantly enhanced as a result of the band alignment of CdSe and TiO2 in electrolyte. Ochratoxin A (OTA), as model analyte, was employed to investigate the performance of the PEC platform. Antibodies of OTA were immobilized on CdSe sensitized electrode by using the classic 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride coupling reactions between -COOH groups on the surfaces of CdSe NPs and -NH2 groups of the antibody. Under the optimized conditions, the photocurrent was proportional to OTA concentration range from 10pg/mL to 50ng/mL with detection limit of 2.0pg/mL. The employed PEC platform established a simple, fast and inexpensive strategy for fabrication of label-free biosensor, which might be widely applied in bioanalysis and biosensing in the future.
Ammonia-oxidizing archaea (AOA) are now implicated in exerting significant control over the form and availability of reactive nitrogen species in marine environments. Detailed studies of specific metabolic traits and physicochemical factors controlling their activities and distribution have not been well constrained in part due to the scarcity of isolated AOA strains. Here, we report the isolation of two new coastal marine AOA, strains PS0 and HCA1. Comparison of the new strains to Nitrosopumilus maritimus strain SCM1, the only marine AOA in pure culture thus far, demonstrated distinct adaptations to pH, salinity, organic carbon, temperature, and light. Strain PS0 sustained nearly 80% of ammonia oxidation activity at a pH as low as 5.9, indicating that coastal strains may be less sensitive to the ongoing reduction in ocean pH. Notably, the two novel isolates are obligate mixotrophs that rely on uptake and assimilation of organic carbon compounds, suggesting a direct coupling between chemolithotrophy and organic matter assimilation in marine food webs. All three isolates showed only minor photoinhibition at 15 µE ? m(-2) ? s(-1) and rapid recovery of ammonia oxidation in the dark, consistent with an AOA contribution to the primary nitrite maximum and the plausibility of a diurnal cycle of archaeal ammonia oxidation activity in the euphotic zone. Together, these findings highlight an unexpected adaptive capacity within closely related marine group I Archaea and provide new understanding of the physiological basis of the remarkable ecological success reflected by their generally high abundance in marine environments.
A novel non-enzymatic immunoassay was designed for ultrasensitive electrochemical detection of carcino-embryonic antigen (CEA) using ?-cyclodextrin functionalized Cu@Ag (Cu@Ag-CD) core-shell nanoparticles as labels and ?-cyclodextrin functionalized graphene nanosheet (CD-GN) as sensor platform. CD-GN has excellent conductivity which promoted the electric transmission between base solution and electrode surface and enhanced sensitivity of immunosensor. In addition, owing to supramolecular recognition of CD-GN for the guest molecule, quite a few synthesized adamantine-modified primary antibodies (ADA-Ab1) were immobilized on the CD-GN by supramolecular host-guest interaction between CD and ADA. Cu@Ag-CD as a signal tag could be captured by ADA-modified secondary antibody (ADA-Ab2) through a host-guest interaction, leading to a large loading of Cu@Ag nanoparticles with high electrical conductivity and catalytic activity. The fabricated immunosensor exhibits excellent analytical performance for the measurement of CEA with wide range linear (0.0001-20 ng/mL), low detection limit (20 fg/mL), good sensitivity, reproducibility and stability, which provide an enormous application prospect in clinical diagnostics.
A new type of carbon charge-transfer magnet, consisting of a fullerene acceptor and single-walled carbon nanotube donor, is demonstrated, which exhibits room temperature ferromagnetism and magnetoelectric (ME) coupling. In addition, external stimuli (electric/magnetic/elastic field) and the concentration of a nanocarbon complex enable the tunabilities of the magnetization and ME coupling due to the control of the charge transfer.
Tumor drug resistance is a major obstacle to cancer chemotherapy. We previously constructed a fusion protein based on two tumstatin-derived sequences named recombinant VBMDM (rVBMDMP). We preliminarily confirmed its inhibition of HUVEC and colon cancer cell growth. The present study further systematically observed the inhibitory effect of rVBMDMP on lung cancer cell growth and analyzed a possible mechanism to provide a theoretical basis for the development of new antitumor protein drugs. The effect of rVBMDMP on human lung adenocarcinoma (A549) and cisplatin-resistant human lung adenocarcinoma (A549/DDP) cell proliferation was evaluated by MTS assay. Hoechst 33342 staining performed together with fluorescence microscopy and immunoblot analysis were used to examine the effects of rVBMDMP on the apoptosis of A549/DDP cells. A protein phosphorylation chip was used to identify changes in rVBMDMP-induced signaling protein phosphorylation. Changes in the phosphatidylinositol 3 kinase (PI3K)/Akt signal transduction pathway and expression of multidrug resistance protein (MRP-2)-related molecules following rVBMDMP treatment in A549/DDP cells were evaluated by western blot analysis. A lung cancer xenograft model was used to evaluate the reversal effect of rVBMDMP on drug-resistance of A549/DDP cell tumors to cisplatin in vivo. The results demonstrated that rVBMDMP increased the phosphorylation of 79 signaling proteins, including focal adhesion kinase (FAK), caspase-6, Fas, FasL and FAF1 and downregulated 30 signaling proteins, including integrin ?V, integrin ?3, PI3K/Akt, NF-?B and MRP-2 compared with the controls. rVBMDMP also increased the sensitivity of A549 and A549/DDP cells to cisplatin and directly induced apoptosis, which may be related to MRP-2 and Bcl-2 downregulation. The effects of growth inhibition and apoptosis induction of rVBMDMP on A549/DDP cells may be related to the inhibition of integrin ?V?3 and PI3K/Akt protein phosphorylation. Finally, we observed an increase in cancer cell sensitivity to cisplatin by rVBMDMP using the A549/DDP cell xenograft model in nude mice. Our study suggests that rVBMDMP may be an effective potential chemotherapy sensitizer and may be a viable drug candidate in anticancer therapies.
Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Salmonella enteritidis CMCC (B) 50041, were used in the antibacterial tests of Cinnamomum longepaniculatum leaf essential oil and its five chemical constituents. The effect of 1, 8-cineole on the ultrastructural structure of the bacteria (S. aureus and E. coli) was also investigated by transmission electron microscopy. The C. longepaniculatum leaf essential oil and the five chemical constituents showed variable levels of inhibition. Their MIC ( minimum inhibitory concentration ) and MBC (minimal bacteriocidal concentration) values were all in the range of 0.781 µL/mL~6.25 µL/mL and 0.781 µL/mL~12.5 µL/mL respectively except ?-terpinene. The MIC values of ?-terpinene against E. coli and S. aureus were all higher than 50 µL/mL, but the MIC and MBC values of ?-terpinene against S. enteritidis was only 3.125 µL/mL. Among them, ?-terpineol possessed the best antibacterial activity. Under the transmission electron microscope, cell size of treated E. coli decreased, cell wall and cell membrane ruptured, and nucleoplasm was reduced and gathered onto the side. After the S. aureus was treated with 1, 8-cineole, the cell size and shape were damaged and nucleus cytoplasm was concentrated or reduced or agglomerated on the side. These results suggest that C. longepaniculatum leaf essential oil and its constituents have excellent antibacterial activities, the antibacterial mechanism of 1, 8-cineole against E. coli and S. aureus might attributable to its hydrophobicity.
The inflammasome has been determined to play an important role in inflammatory diseases in recent years. Absent in melanoma 2 (AIM2), an inflammasome that recognizes cytoplasmic DNA, has recently been identified as a critical regulator of immune responses. In this study, we explored whether AIM2 was expressed in human dental pulp and defined the role of AIM2 in regulating interleukin (IL)-1? secretion. We demonstrated that AIM2 was only detected in the odontoblast layer of healthy dental pulp, whereas strong expression was observed in inflamed dental pulp. Stimulation with interferon gamma (IFN-?) and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1? secretion in human dental pulp cells (HDPCs) in a time- and dose-dependent manner. Moreover, the knockdown of AIM2 downregulated both cleaved-caspase-1 expression and IL-1? release in HDPCs. These results suggest that AIM2 expressed in human dental pulp plays an important role in the immune defense by activating the inflammasome signaling pathway.
The aim of this study was to assess whether modulated electro-hyperthermia (mEHT) can induce an abscopal effect and thereby enhance the antitumor effects of immunotherapy. We used an intratumoral dendritic cell (DC) injection and mEHT to treat C3H/He mice inoculated with squamous cell carcinoma SCCVII cells in the left leg, and we assessed the whole body antitumor effects. Tumors were examined every two or three days in order to assess growth inhibition. The tumor-draining lymph nodes were removed to enable flow cytometric analysis of CD3+ and CD8+ cells, whereas immunohistochemistry was used to assess CD8, S100 and Foxp3 expression in the tumors. Additionally, GP96 expression in the tumors from the different treatment groups was measured. In the control group, the mean tumor volume was larger than that in other groups. These results indicated that the combination therapy of an intratumoral DC injection and mEHT evoked systemic antitumor activity. A larger number of CD3+ and CD8+ cells were detected by flow cytometric analysis in the DC plus mEHT treatment group. Tumor tissue immunostaining showed that CD8 and S100 were more strongly expressed in the DC plus mEHT treatment group, although Foxp3 expression was much higher in the control group. The GP96 gene expression level in the mEHT group was significantly different from the expression level in the control group. An abscopal effect may be induced by mEHT, and the effect of immunotherapy with DCs was strongly enhanced by the overexpression of GP96. GP96 is thought to be one of the molecules explaining the abscopal effect. Direct intratumoral administration of DCs and mEHT may be a feasible future treatment strategy.
The objective of this study was to evaluate the nitrous oxide (N2O) emissions in partial nitrifying and full nitrifying granular sludge reactors treating ammonium-rich wastewater. During stable operation, there was no significant difference of NH4(+)-N removal efficiencies between the two granular reactors. Nitrate and nitrite were the main effluent nitrogen species of the two reactors, and nitrite accumulation rate of partial nitrifying reactor was high of 87.79±2.03%. However, partial nitrifying granular-reactor had better total nitrogen removal efficiency (41.84±3.35%) than that of full nitrifying granular-reactor (19.91±2.12%). According to typical cycles, the N2O emission amount per cycle of partial nitrifying reactor account for 11.48% of the incoming nitrogen load, which was 1.5 times higher than that of full nitrifying reactor (7.47%). The obtained results could provide more information for understanding of N2O emission in granular sludge systems.
A novel and sensitive electrochemical immunosensor for ultrasensitive detection of pancreatic cancer biomarker carbohydrate antigen 199 (CA199) was proposed by using Au@Cu(x)OS yolk-shell nanostructures with porous shells as labels for signal amplification. Au@Cu(x)OS yolk-shell nanostructures exhibit high electrocatalytic activity toward the reduction of hydrogen peroxide (H2O2) as analytical signal. Moreover, secondary antibody (Ab2) can adsorb on the surface of Au@Cu(x)OS with porous shells which has large surface area and could greatly increase the probability of Ab2-antigen interactions thereby leading to higher sensitivity. Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), containing abundant amine groups, was supported Au nanoparticles as a support platform to immobilize the primary antibody (Ab1). The resulting sensing interface of rGO-TEPA/AuNPs could provide a large electroconductive surface area, allowing high loadings of the biological recognition elements as well as the occurrence of electrocatalytic and electron-transfer processes. Under optimal conditions, the immunosensor exhibited a wide linear response to CA199 ranging from 0.001 to 12 U/mL with a low detection limit of 0.0005 U/mL. The designed immunosensor displayed good precision, high sensitivity, acceptable stability and reproducibility, and has been applied to the analysis of serum with satisfactory results. The proposed method provides a new promising platform of clinical immunoassay for other biomolecules.
A novel and ultrasensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of alpha fetoprotein (AFP) using multifunctional mesoporous silica (MCM-41) as platform and label for signal amplification. MCM-41 has high specific surface area, high pore volume, large density of surface silanol groups (SiOH) and good biocompatibility. MCM-41 functionalized with 3-aminopropyltriethoxysilane (APTES), gold nanoparticles (Au NPs) and toluidine blue (TB) could enhance electrochemical signals. Moreover, primary antibodies (Ab1) and secondary antibodies (Ab2) could be effectively immobilized onto the multifunctional MCM-41 by the interaction between Au NPs and amino groups (-NH2) on antibodies. Using multifunctional MCM-41 as a platform and label could greatly simplify the fabrication process and result in a high sensitivity of the designed immunosensor. Under optimal conditions, the designed immunosensor exhibited a wide liner range from 10(-4) ng/mL to 10(3) ng/mL with a low detection limit of 0.05 pg/mL for AFP. The designed immunosensor showed acceptable selectivity, reproducibility and stability, which could provide potential applications in clinical monitoring of AFP.
Shensong Yangxin Capsule (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the effect of SSYX on interstitial fibrosis in diabetic cardiomyopathy is unknown. The objective of this study was to investigate the effects of SSYX on myocardial fibrosis in diabetic rats.
Aim:Endogenous carbon monoxide (CO) has been shown to modulate inflammation and inhibit cytokine production both in vivo and in vitro. The aim of this study was to examine whether exogenous carbon monoxide could suppress the vitality of Escherichia coli (E coli) and improve the survival rate in an E coli-induced murine sepsis model.Methods:ICR mice were infected with E coli, and immediately injected intravenously with carbon monoxide releasing molecule-2 (CORM-2, 8 mg/kg) or inactive CORM-2 (8 mg/kg). The survival rate was monitored 6 times daily for up to 36 h. The blood samples, liver and lung tissues were collected at 6 h after the infection. Bacteria in peritoneal lavage fluid, blood and tissues were enumerated following culture. Tissue iNOS mRNA expression was detected using RT-PCR. NF-?B expression was detected with Western blotting.Results:Addition of CORM-2 (200 and 400 ?mol/L) into culture medium concentration-dependently suppressed the growth of E coli and decreased the colony numbers, but inactive CORM-2 had no effect. Treatment of the infected mice with CORM-2 significantly increased the survival rate to 55%, while all the infected mice treated with inactive CORM-2 died within 36 h. E coli infection caused severe pathological changes in liver and lungs, and significantly increased serum transaminases, lipopolysaccharide, TNF-? and IL-1? levels, as well as myeloperoxidase activity, TNF-? and IL-1? levels in the major organs. Meanwhile, E coli infection significantly increased the number of colonies and the expression of iNOS mRNA and NF-?B in the major organs. All these abnormalities were significantly attenuated by CORM-2 treatment, while inactive CORM-2 was ineffective.Conclusion:In addition directly suppressing E coli, CORM-2 protects the liver and lungs against E coli-induced sepsis in mice, thus improving their survival.
Diagnosis of depth of anaesthesia (DoA) plays an important role in treatment and drug usage in the operating theatre and intensive care unit. With the flourishing development of analysis methods and monitoring devices for DoA, a small amount of physiological data had been stored and shared for further researches. In this paper, a critical care monitoring (CCM) system for DoA monitoring and analysis was designed and developed, which includes two main components: a physiologic information database (PID) and a DoA analysis subsystem. The PID, including biologic data and clinical information was constructed through a browser and server model so as to provide a safe and open platform for storage, sharing and further study of clinical anaesthesia information. In the analysis of DoA, according to our previous studies on approximate entropy, sample entropy (SampEn) and multi-scale entropy (MSE), the SampEn and MSE were integrated into the subsystem for indicating the state of patients underwent surgeries in real time because of their stability. Therefore, this CCM system not only supplies the original biological data and information collected from the operating room, but also shares our studies for improvement and innovation in the research of DoA.
The tumor suppressor p53 plays an important role in tumorigenesis. Besides inducing apoptosis, it regulates cellular senescence, which constitutes an important barrier to tumorigenesis. The mechanism of regulation of cellular senescence by p53 and its downstream pathway are poorly understood. Here, we report that the ubiquitin domain-containing 1 gene (UBTD1), a new downstream target of p53, induces cellular senescence and acts as a novel tumor suppressor by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular senescence induced by serial passaging of culture, as well as by exposure to DNA-damaging drugs that induce premature senescence. Overexpression of UBTD1 induces senescence in human fibroblasts and cancer cells, and attenuation of the transformed phenotype in cancer cells. UBTD1 is downregulated in gastric and colorectal cancer tissues, and its lower expression correlates with a more aggressive phenotype and worse prognosis. Multivariate analysis revealed that UBTD1 expression was an independent prognostic factor for gastric cancer patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein. Importantly,UBTD1 and p53 function mutually depend on each other in regulating cellular senescence and proliferation. Thus, our data suggests that upon DNA damage, p53 induction by UBTD1 creates a positive feedback mechanism to further increase p53 expression. Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumorigenesis.
A sandwich electrochemical immunosensor is described for carbohydrate antigen 72-4 (CA72-4) based on a dual amplification strategy with nanoporous gold (NPG) film as the sensor platform and polyaniline-Au asymmetric multicomponent nanoparticles (PANi-Au AMNPs) as labels. In this study, the second anti-CA72-4 antibody (Ab2) adsorbed onto the Au of the PANi-Au AMNPs, which could be simply synthesized by interfacial reaction and have many characteristics of polyaniline and Au nanoparticle, such as well-controlled size, high conductivity, biocompatibility and catalysis. NPG film was used as electrode substrate material to fix a large number of antibodies, due to its unique properties: good biocompatibility, high conductivity, large surface area, and stability. The synergetic of NPG film and PANi-Au AMNPs could increase signal response, and significantly improve sensitivity of the immunosensor. The proposed immunosensor exhibited a wide linear range from 2 to 200U/mL, with a detection limit of 0.10U/mL CA72-4, good reproducibility, selectivity and stability. This new type of labels for immunosensors may provide many potential applications in the detection of carbohydrate antigen in immunoassays.
Octadecanoic acid-3,4-tetrahydrofuran diester, isolated from neem (Azadirachta indica) oil, exhibited potent acaricidal activity against Sarcoptes scabiei var. cuniculi. In this paper, the acaricidal mechanism of octadecanoic acid-3,4-tetrahydrofuran diester against Sarcoptes scabiei var. cuniculi was evaluated based on pathologic histology and enzyme activities. The results showed that after compound treatment for 24h at a concentration of 20mg/mL, the lesions of mites were prominent under transmission electron microscopy. The lesions consisted of the lysis of dermis cell membranes and cell nuclear membranes, mitochondrial morphological abnormalities, the drop of spinal disorders, and mitochondrial vacuolization. The activity of superoxide dismutase (SOD), peroxidase (POD), glutathione-s-transferases (GSTs), and Ca(2+)-ATPase of mites significantly changed after treatment with octadecanoic acid-3,4-tetrahydrofuran diester compared with the control group. The activities of SOD, POD, and Ca(2+)-ATPase were significantly suppressed, whereas that of GSTs was activated. These results indicated that the mechanism of the acaricidal activity of octadecanoic acid-3,4-tetrahydrofuran diester was mainly achieved through interference with the energy metabolism of mites, thus resulting in insect death.
Oxidative stress is a causal factor and key promoter of a variety of cardiovascular diseases associated with apoptotic cell death by causing deregulation of related genes. Though carvedilol, a ?-adrenergic blocker, has been shown to produce cytoprotective effects against cardiomyocyte apoptosis, the mechanisms are not fully understood. The present study was designed to investigate whether the beneficial effects of carvedilol are related to microRNAs which have emerged as critical players in cardiovascular pathophysiology via post-transcriptional regulation of protein-coding genes. In vivo, we demonstrated that carvedilol ameliorated impaired cardiac function of infarct rats and restored miR-133 expression. In vitro, carvedilol protected cardiomyocytes from H2O2 induced apoptosis detected by TUNEL staining and MTT assays, and increased miR-133 expression in cardiomyocytes. Overexpression of miR-133, a recognized anti-apoptotic miRNA, produced similar effects to carvedilol: reduction of reactive oxygen species (ROS) and malondialdehyde (MDA) content and increment of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) level, so as to protect cardiomyocytes from apoptosis by downregulating caspase-9 and caspase-3 expression in the presence of H2O2. Transfection with AMO-133 (antisense inhibitor oligodeoxyribonucleotides) alone abolished the beneficial effects of carvedilol. Caspase-9-specific inhibitor z-LEHD-fmk, caspase-3-specific inhibitor z-DEVD-fmk, caspase-9 siRNA and caspase-3 siRNA were used to establish caspase-3 as a downstream target of miR-133. In conclusion, our data indicated that carvedilol protected cardiomyocytes by increasing miR-133 expression and suppressing caspase-9 and subsequent apoptotic pathways.
A new electrochemical dual amplification sandwich immunosensor (DASI) was designed for ultrasensitive and accurate detection of the breast cancer susceptibility gene based on the combination of N-doped graphene, hydroxypropyl chitosan and Co3O4 mesoporous nanosheets. N-doped graphene has better electroconductibility than traditional graphene. It is an ideal electrochemical material with a large specific surface area and low resistance. Hydroxypropyl chitosan replaces the pure chitosan in immobilization of the sensor to achieve the sensitivity increase. Co3O4 mesoporous nanosheets can enhance the effective area of the immunoreaction. This kind of dual amplification sandwich immunosensor was first used for the detection of the breast cancer susceptibility gene. It has a wide linear response range of 0.001-35 ng mL(-1) and a minimum detection limit of 0.33 pg mL(-1). It was demonstrated that the stability, selectivity and reproducibility of the sensor were acceptable. The fabricated immunosensor shows great potential applications in early disease diagnosis.
Currently, growing attention has been paid to the sensitive determination and removal of Cu2+ because excessive levels of Cu2+ could do harm to organisms. Herein, a novel diethanolamine-modified magnetic fluorescent Fe3O4@ZnS nanoparticle (MFNP) for simultaneous detection and removal of Cu2+ was designed and synthesized through dithiocarbamate linkage strategy. The characterization of MFNP was confirmed by transmission electron microscope (TEM), infrared (IR) and emission spectra. The results showed that MFNP could quantificationally detect Cu2+ with high sensitivity and selectivity under a broad pH range (pH 4.5-9). The removal of Cu2+ was achieved by the aggregation-induced sedimentation (AIS) strategy and by external magnetic field.
In the present study, a kind of graphenes magnetic material (Fe3O4-GS) was prepared by compositing graphene sheet with ferroferric oxide, and shown to be effective for removing Cr(VI), Pb(II), Hg(II), Cd(II) and Ni(II) ions from aqueous solution. The synthesized sorbent was characterized by SEM, TEM, FTIR, XRD, XPS and BET, respectively. The pHZPC value of the sorbent was estimated to be 3.5 by alkaline-titration methods. Fe3O4-GS can be simply recovered from water with magnetic separation at low magnetic field within one minute. The sorption capacities of the metals were 17.29, 27.95, 23.03, 27.83 and 22.07 mg g(-1) for Cr(VI), Pb(II), Hg(II), Cd(II) and Ni(II), respectively. Kinetic data showed good correlation with pseudo-second-order equation and the Freundlich model was found to fit for the isotherm data of all the heavy metal ions. It was found that the metals sorption was accomplished mainly via chelation or ion exchange. The results of thermodynamic studies illustrate that the adsorption process was endothermic and spontaneous in nature.
A novel nonenzymatic sandwich-type electrochemical immunosensor has been developed to detect squamous cell carcinoma antigen (SCCA). Nitrogen-doped graphene sheet (N-GS) was used to increase capacity of capturing primary antibodies (Ab1). Carbon-supported Pd-Au binary nanoparticles (Pd-Au/C) were synthesized and used to label secondary antibodies (Ab2). The specific binding of SCCA and antibodies enabled a quantitative attachment of Pd-Au/C on the electrode surface. Electrocatalytic analysis showed that the prepared Pd-Au/C exhibit excellent electrocatalytic activity towards hydrogen peroxide (H2O2). We use current response of electrocatalytic labels Pd-Au/C to detect the concentration of SCCA. The unique nonenzymatic immunosensor exhibits a relatively wide linear range from 0.005 to 2 ng mL(-1) and high sensitivity with a low detection limit of 1.7 pg mL(-1). The immunsensor also shows good reproducibility (4.2%) and stability (5.8%), which makes it an enormous application prospect in clinical research.
Transforming growth factor-? (TGF-?) is upregulated in advanced stages of prostate cancer and strongly correlated with metastasis. However, the effect of TGF-? on epithelial-mesenchymal transition (EMT) in prostate cancer and the underlying mechanisms remain unclear. Recently, microRNAs have emerged as new regulators of EMT. This study found that treatment of DU145 cells with TGF-? suppressed the expression of epithelial marker E-cadherin and increased the expression of mesenchymal marker Vimentin as well as changed the cell morphology from cobblestone shape to spindle shape. The level of miR-124 was downregulated by TGF-? in several different cancer cell lines. Enforced expression of miR-124 abolished TGF-?-induced EMT. Slug was proven to be a target of miR-124 and mediated the inhibitory effect of miR-124 on TGF-?-induced EMT. Furthermore, overexpression of miR-124 reduced the migratory and invasive capacity of TGF-?-treated DU145 cells. In conclusion, our findings suggest that miR-124 inhibits TGF-?-induced EMT in DU145 cells by targeting Slug. Thus, miR-124 may be a potential target for prostate cancer therapeutic intervention.
A new sandwich photoelectrochemical (PEC) sensing strategy was proposed for the first time based on the increasing photocurrent of water-soluble polythiophene sensitized g-C3N4 nanosheet (PT-Cl/g-C3N4) in the presence of copper(II) (Cu(2+)), which was doped on the surface of titanium dioxide as labels for multi-amplification. Herein, the photoactive films of PT-Cl/g-C3N4 is employed as the photoactive antibody (Ab1) immobilization matrix for the subsequent sandwich-type antibody-antigen affinity interactions. Upon the presence of antigen (Ag), greatly enhanced photocurrent could be triggered in the PEC platform by the labels of second antibody (Ab2) of Cu(2+) doped titanium dioxide (Cu(2+)-TiO2). As a result of the multi-amplification in this Cu(2+)-TiO2 enhanced PT-Cl/g-C3N4-based PEC immunoassay, it possesses excellent analytical performance. The antigen could be detected from 0.01 pg mL(-1) to 100.0 ng mL(-1) with a detection limit of 5 fg mL(-1). This work opens up g-C3N4 nanosheet applied in PEC sensing. More importantly, the strategy of specific positive effect of Cu(2+) on the photocurrent of g-C3N4 opens an alternative horizon for PEC sensing.
Highly sensitive and enzyme-free detection of melanoma adhesion molecule antigen (CD146) remains a challenge in clinical diagnosis. The prepared immunosensor, based on amination graphene (GS-NH2) and mesoporous nano-Co3O4 sheet combined with gold nanoparticles (Au/Co3O4), exhibited significantly increased electron transfer, high sensitivity and stability to CD146. Au/Co3O4 can increase the contact surface between the antibody and Au nanoparticles attached on Co3O4 than mesoporous Co3O4 only. And the mesoporous Co3O4 nanosheet can capture more biomolecules to enhance the sensitivity due to the large effective specific area. Amperometric i-t curve and electrochemical impedance spectroscopy (EIS) were used to characterize the recognition of CD146. This novel immunosensor, works well over a broad linear range of 0.01-15ng/mL, with a low detection limit of 3.4pg/mL (S/N=3). The immunosensor was evaluated for the determination of human serum sample, and received a satisfactory result. The developed immunosensor provides a promising approach for clinical research and diagnostic applications.
A novel, sensitive electrochemical immunosensor for simultaneous determination of squamous cell carcinoma associated antigen (SCC-Ag) and carcinoembryonic antigen (CEA) for the combined diagnosis of cervical cancer was designed. The amplification strategy for electrochemical immunoassay was based on poly[3-(1,1'-dimethyl-4-piperidine-methylene) thiophene-2,5-diylchloride] (PDPMT-Cl) and functionalized mesoporous ferroferric oxide nanoparticles (Fe3O4 NPs). PDPMT-Cl dispersed in chitosan solution with enhanced electrical conductivity and solubility was used as matrices to immobilize the first antibodies. Different redox probes (thionine (Th) and ferrocenecarboxylic acid (Fca)) functionalized Fe3O4 NPs incubated with two kinds of secondary antibodies to fabricate the labels. Using an electrochemical analysis technique, two well-separated peaks were generated by Th and Fca, making the simultaneous detection of two analytes on the electrode possible. Under optimized conditions, this method showed wide linear ranges of three orders of magnitude with the detection limits of 4 pg mL(-1) and 5 pg mL(-1), respectively. The disposable immunosensor possessed excellent clinical value in cervical cancer screening as well as convenient point-of-care diagnostics.
A novel electrochemical immunosensor for sensitive detection of carbohydrate antigen 15-3 (CA15-3) based on dual signal amplification strategy of ionic liquid functionalized graphene and Cd(2+)-functionalized nanoporous TiO2 (f-TiO2-Cd(2+)) has been developed. Ionic liquid functionalized graphene was used to anchor primary CA15-3 antibody (Ab1). f-TiO2-Cd(2+) was employed to immobilize secondary cancer antigen 15-3 (CA15-3) antibody (Ab2) and the resulting nanocomposite (Ab2-f-TiO2-Cd(2+)) was used as trace tag for signal amplification. The fabricated immumosensor displayed a wide range of linear response (0.02-60 U/mL), ultra-low detection limit (0.008 U/mL), good reproducibility, selectivity and stability towards CA15-3. The good performance of the immunosensor can be attributed to (1) high surface-to-volume ratio of graphene which allows high-level immobilization of Ab1, (2) excellent biocompatibility and electron transfer rate originating from ionic liquid functionalized graphene, (3) a highly specific surface area of nanoporous TiO2 that facilitates the adsorption of high amount of Cd(2+) for signal amplification.
An ultrasensitive sandwich-type electrochemical immunosensor for the quantitative detection of carcinoembryonic antigen (CEA) was designed based on a novel signal amplification strategy. Gold nanoparticles decorated mesoporous silica KIT-6 (Au@KIT-6) with large specific surface area and good adsorption properties was used as a label matrix to immobilize both the secondary antibodies (Ab2) and the electron transfer mediator toluidine blue (TB). Ab2 was loaded on KIT-6 due to the presence of gold nanoparticles (Au NPs) and TB was loaded on KIT-6 by physical adsorption. Ionic liquids (ILs) doped carboxymethyl chitosan (CMC) was used to prevent the leak of TB and facilitate the electron transfer. For the immobilization of primary antibodies (Ab1), gold nanoparticles decorated 3-aminopropyltriethoxysilane functionalized graphene sheets (Au@APTES-GS) were used as transducing materials to modify glassy carbon electrodes (GCE). High sensitivity was achieved for the designed immunosensor based on this novel signal amplification strategy. Under optimal conditions, the immunosensor exhibited an extremely low detection limit of 3.3 fg/mL and wide liner range from 10(-5) ng/mL to 10(2) ng/mL for CEA. Moreover, it exhibited good selectivity, acceptable reproducibility and stability, indicating potential application promising in clinical monitoring of tumor biomarkers.
IL-4R?, the common receptor component for IL-4 and IL-13, plays a critical role in IL-4- and IL-13-mediated signaling pathways that regulate airway inflammation and remodeling. However, the regulatory mechanisms underlying IL-4R? turnover and its signal termination remain elusive.
A novel label-free amperometric immunosensor for sensitive detection of nuclear matrix protein 22 (NMP22) was developed based on Au-Pt bimetallic nanostructures, which were prepared by combining top-down with bottom-up strategies. Nanoporous gold (NPG) was prepared by "top-down" dealloying of commercial Au/Ag alloy film. After deposition of NPG on an electrode, Pt nanoparticles (PtNPs) were further decorated on NPG by "bottom-up" electrodeposition. The prepared bimetallic nanostructures combine the merits of both NPG and PtNPs, and show a high electrocatalytic activity towards the reduction of H2O2. The label-free immunosensor was constructed by directly immobilizing antibody of NMP22 (anti-NMP22) on the surface of bimetallic nanostructures. The immunoreaction induced amperometric response could be detected and negatively correlated to the concentration of NMP22. Bimetallic nanostructure morphologies and detection conditions were investigated to obtain the best sensing performance. Under the optimal conditions, a linear range from 0.01ng/mL to 10ng/mL and a detection limit of 3.33pg/mL were obtained. The proposed immunosensor showed high sensitivity, good selectivity, stability, reproducibility, and regeneration for the detection of NMP22, and it was evaluated in urine samples, receiving satisfactory results.
A novel label-free amperometric immunosensor is proposed for the ultrasensitive detection of zearalenone (ZEN) based on mesoporous carbon (MC) and trimetallic nanorattles (core/shell particles with movable cores encapsulated in the shells). The nanorattles are composed of special Au-core and imperfect AgPt-shell structure (Au@AgPt). The Au@AgPt nanorattles are loaded onto the MC by physical adsorption. The structure of the Au@AgPt nanorattles was characterized by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Energy dispersive X-ray spectroscopy (EDS) confirmed the composition of the synthesized nanorattles. Compared with monometallic and bimetallic nanoparticles (NPs), Au@AgPt nanorattles show a higher electron transfer rate due to the synergistic effect of the Au, Ag and Pt NPs. MC further improves the sensitivity of the immunosensor because of its extraordinarily large specific surface area, suitable pore arrangement and outstanding conductivity. The large specific surface area of MC and MC@Au@AgPt were characterized by the BET method. ZEN antibodies are immobilized onto the nanorattles via Ag-NH2 bonds and Pt-NH2 bonds. Cyclic voltammetry and square wave voltammetry were used to characterize the recognizability of ZEN. Under optimum experimental conditions, the proposed immunosensor exhibited a low detection limit (1.7 pg mL(-1)), a wide linear range (from 0.005 to 15 ng mL(-1)) as well as good stability, reproducibility and selectivity. The sensor can be used in clinical analysis.
Determination of squamous cell carcinoma antigen (SCCA) in human serum plays an important role in diagnosis of cervical squamous cell carcinoma. In this work, Au/Ag/Au core/double shell nanoparticles (Au/Ag/Au NPs) were prepared by a simple approach and were used as novel enzyme-mimetic labels for development of a sandwich-type electrochemical immunosensor for SCCA. The nanostructure of Au/Ag/Au NPs could be well confirmed by transmission electron microscope (TEM) and UV-vis spectra. Au NPs decorated mercapto-functionalized graphene sheets (Au@SH-GS) were used as platform for immobilization of primary antibody (Ab1), while Au/Ag/Au NPs were employed as labels of secondary antibody (Ab2). Due to the excellent electrocatalytic activity of Au/Ag/Au NPs towards the reduction of hydrogen peroxide (H2O2), electrochemical amperometric responses to SCCA were achieved after the immuno-reaction. Under optimum conditions, the electrochemical immunosensor exhibited a wide linear range from 0.5 pg/mL to 40 ng/mL with a low detection limit of 0.18 pg/mL for SCCA. The designed immunosensor displayed an excellent analytical performance with good reproducibility, high selectivity and stability.
Coronary heart disease (CHD) is a major cause of morbidity and mortality, and cardiac rehabilitation (CR) is still not well developed in mainland China. The objective of this study is to investigate the barriers associated with those seeking cardiac rehabilitation (CR) and to explore appropriate secondary prevention modalities tailored to the needs of Chinese patients with coronary heart disease (CHD).
Whether or not migraine can cause cumulative brain alterations due to frequent migraine-related nociceptive input in patients is largely unclear. The aim of this study was to characterize longitudinal changes in brain activity between repeated observations within a short time interval in a group of female migraine patients, using resting-state functional magnetic resonance imaging.
In this study, a novel sensitive electrochemiluminescence (ECL) immunosensor was constructed by carboxyl graphene (GR) for enhancing luminol-O2 system emission. Here, carboxyl GR was used to enhance the ECL intensity of luminol that had excellent electron transfer ability and good solubility. The sensing platform was constructed by depositing carboxyl GR on electrodes and immobilizing antibodies on the surface of carboxyl GR through amidation. The specific immunoreaction between ?-fetoprotein (AFP) and antibodies resulted in a decrease of ECL intensity, and the intensity decreased linearly with AFP concentrations in the range of 5 pg ml(-1) to 14 ng ml(-1) with a detection limit of 2.0 pg ml(-1). The proposed immunosensor exhibits high specificity, good reproducibility, and longtime stability. It may become a promising technique for protein detection.
A novel label-free electrochemiluminescence (ECL) immunosensor was developed for the detection of squamous cell carcinoma antigen (SCCA) based on nanocomposites of semiconductor carboxylated graphitic carbon nitride (g-C3N4) and graphene (g-C3N4-graphene). The ECL intensity of carboxylated g-C3N4 was much enhanced after being combined with graphene which had excellent electron-transfer ability. The sensing platform was constructed by depositing g-C3N4-graphene on electrodes and immobilizing antibodies on the surface of carboxylated g-C3N4 through amidation. The specific immunoreaction between SCCA and antibody resulted in the decrease of ECL intensity and the intensity decreased linearly with the logarithm of SCCA concentration in the range of 0.025-10 ng mL(-1) with a detection limit of 8.53 pg mL(-1). The developed ECL immunosensor exhibited high sensitivity, good reproducibility and long-term stability, which possessed great potential for cancer detection in clinical laboratory diagnosis.
A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.
Bimetallic hierarchical nanostructures have attracted increasing attention for biosensing applications due to their higher electrocatalytic activity and better biocompatibility. In this work, we developed a novel sandwich-type nonenzymatic electrochemical immunosensor for cancer biomarker carbohydrate antigen 15-3 (CA15-3). Hierarchical nanoporous PtFe alloys were used as carriers of the signaling antibody anti-CA15-3 in order to achieve an signal amplification. The immunosensor is constructed by using a graphene as platform and using mesoporous PtFe alloy as labels. The electrochemical signal of the immunosensor was based on the high-electrocatalytic activity of PtFe alloy for the electro-oxidation of H2O2. Under optimal conditions, this method could detect CA15-3 ranging from 0.002 to 40 U/mL with a low detection limit of 3 × 10(-4)U/mL. This immunosensor showed good accuracy, stability and fabrication reproducibility. The hierarchical nanoporous metal materials-based immunoassay provides a promising ultrasensitive immunoassay approach for clinical applications.
Constructions of versatile electroactive labels are key issues in the development of electrochemical immunosensors. In this study, copper-doped titanium dioxide nanoparticle (Cu@TiO2) was synthesized and used as labels for fabrication of sandwich-type electrochemical immunosensors on glassy carbon electrode (GCE). Due to the presence of copper ions, Cu@TiO2 shows a strong response current when coupled to an electrode. The prepared nanocomposite also shows high electrocatalytic activity towards reduction of hydrogen peroxide (H2O2). The dual functionality of Cu@TiO2 enables the fabrication of immunosensor using different detection modes, that is, square wave voltammetry (SWV) or chronoamperometry (CA). While Cu@TiO2 was used as labels of secondary antibodies (Ab2), carboxyl functionalized graphene oxide (CFGO) was used as electrode materials to immobilize primary antibodies (Ab1). Using human immunoglobulin G (IgG) as a model analyte, the immunosensor shows high sensitivity, acceptable stability and good reproducibility for both detection modes. Under optimal conditions, a linear range from 0.1 pg/mL to 100 ng/mL with a detection limit of 0.052 pg/mL was obtained for SWV analysis. For CA analysis, a wider linear range from 0.01 pg/mL to 100 ng/mL and a lower detection limit of 0.0043 pg/mL were obtained. The proposed metal ion-based enzyme-free and noble metal-free immunosensor may have promising applications in clinical diagnoses and many other fields.
To investigate the effect of ?-terpineol on cell proliferation and apoptosis of human hepatoma BEL-7402 cells to elucidate its molecular mechanism. Here, BEL-7402 cells were treated with various concentrations (40, 80, 160, 320 and 640 ?g/ml) of ?-terpineol for 48 h, cell proliferation was determined by 3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyl tetrazolium bromides (MTT) assay. Cell colony inhibition was determined by soft agar assay. Apoptosis and possible molecular mechanisms were evaluated by morphological observation, flow cytometry analysis, and DNA fragmentation assay. The ?-terpineol significantly suppressed BEL-7402 cell proliferation in a dose-dependent manner. Characteristic morphological and biochemical changes associated with apoptosis such as cells shrinkage, deformation and vacuolization of mitochondria, nuclear chromatin condensation and fragmentation, formation of apoptotic bodies were observed after BEL-7402 cells treated with ?-terpineol for 24 h and 48 h. Cell cycle were displayed by flow cytometry analysis, the ?-terpineol treatment resulted in accumulation of cells at G1 or S phase and a blockade of cell proliferation compared to control group. Treating BEL-7402 cells with 320 ?g/ml of ?-terpineol for 36 h and 48 h, a typical apoptotic "DNA ladder" was observed using DNA fragmentation assay. The present study demonstrated that possible anti-cancer mechanism of ?-terpineol on human hematomas cells is through inducing cell apoptosis to suppress tumor cell growth.
The aim of this study was to study the anti-hepatoma effect of safrole and elucidate its molecular mechanism, the human hepatoma BEL-7402 cells were incubated with various concentrations (40, 80, 160, 320 and 640 ?g/ml) of safrole and the cell proliferation and apoptosis were evaluated. The results showed that both the cell proliferation determined by 3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyl tetrazolium brominde (MTT) assay and cell colony determined by soft agar assay were significantly suppressed by safrole in a dose-time-dependent manner. Characteristic morphological and biochemical changes associated with apoptosis, including cells shrinkage, deformation and vacuolization of mitochondria, nuclear chromatin condensation and fragmentation, formation of apoptotic bodies were observed when treated with safrole for 24 h and 48 h. Cell cycle changes evaluated by flow cytometry analysis showed that the safrole could induce accumulation of cells arrested at G1 and S phases of the cell cycle. These results demonstrated that safrole is potent anti-hepatoma agent and the underlying mechanism may be attributed to suppress tumor cell growth by inducing cell apoptosis.
The effects of acute and subacute toxicity of 1,8-cineole in Kunming mice were studied. After acute oral administration, the LD50 value (95% CL) was 3849 mg/kg (3488.8~4247.1 mg/kg). In the subacute toxicity study, there were no significant differences in body weight and relative organ weight between the control group and 1,8-cineole treatment groups. The histopathological examinations showed that granular degeneration and vacuolar degeneration appeared in liver and kidney tissue after administration of high dose of 1,8-cineole. Under electron microscopy, a series of ultrastructural changes were observed: The electron microscopy assays indicated that the influence of 1,8-cineole on the target organ at the subcellular level were mainly on the mitochondria, endoplasmic reticulum and other membrane type structure of liver and kidney.
This study was purposed to investigate the effect of mutation and single nucleotide polymorphism (SNP) of suppressor of cytokine signaling (SOCS) on the typical myeloproliferative neoplasms(MPN) and its mechanism. The mutation and SNP of SOCS1, SOCS2, SOCS3 genes in 100 MPN patients were detected by RT-PCR and direct sequencing. The results showed that among 100 cases there were 21 cases with A?C polymorphism in the 63th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 18 cases with A?C polymorphism in the 1779th site nucleotide of the 15 SOCS3 exon, 49 cases with A?G polymorphism in the 2249th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 39 cases with T?C polymorphism in the 2366th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 9 cases with T?C polymorphism in the exon of 15 SOCS2 gene (SNP library no reported). SOCS3 SNP was found in patients with significantly advanced age at diagnosis, the leukocyte count and platelet level were higher than those in patients with wild type, JAK2V617 mutations was found in 87.65% SOCS3 SNP. It is concluded that the SOCS may be an important target for anticancer therapy, the single nucleotide polymorphism of SOCS may involve to pathogenesis of MPN.
Using electrochemical charge injection, the fluorescence lifetimes of negatively charged core/shell CdTe/CdSe QDs are measured as a function of core size and shell thickness. It is found that the ensemble negative trion lifetimes reach a maximum (?4.5 ns) for an intermediate shell thickness. This leads to the smallest particles (?4.5 nm) with the brightest trion to date. Single dot measurements show that the negative charge suppresses blinking and that the trion can be as bright as the exciton at room temperature. In contrast, the biexciton lifetimes remain short and exhibit only a monotonous increase with shell thickness, showing no correlation with the negative trion decays. The suppression of the Auger process in small negatively charged CdTe/CdSe quantum dots is unprecedented and a significant departure from prior results with ultrathick CdSe/CdS core/shell or dot-in-rod structures. The proposed reason for the optimum shell thickness is that the electron-hole overlap is restricted to the CdTe core while the electron is tuned to have zero kinetic energy in the core for that optimum shell thickness. The different trend of the biexciton lifetime is not explained but tentatively attributed to shorter-lived positive trions at smaller sizes. These results improve our understanding of multiexciton recombination in colloidal quantum dots and may lead to the design of bright charged QDs for more efficient light-emitting devices.
Recently, much attention has been paid to the selective detection and removal of Cu(2+) because an excess of Cu(2+) can harm the environment and living systems. Herein, we developed a novel water-soluble di-2-picolylamine/proline co-modified Fe3O4@ZnS magnetic fluorescent nanoparticle (MFNP-Cu) for the selective detection and removal of Cu(2+) through a dithiocarbamate linkage strategy. The characterization of MFNP-Cu was confirmed by x-ray diffraction (XRD), transmission electron microscope (TEM), magnetization hysteresis loops, infrared (IR) and emission spectra. The results showed that MFNP-Cu could quantifiably detect Cu(2+) with high sensitivity and selectivity over a broad pH range (pH 4.1-9). The maximum adsorption capacity of MFNP-Cu was calculated to be about 517.9 mg g(-1), which is higher than previously reported. This excellent property was investigated by kinetics equilibrium and thermodynamic studies. Moreover, the removal properties of MFNP-Cu toward Cu(2+) from contaminated water samples was achieved by an external magnetic field.
A continuous observation campaign was carried out with the GC5000 volatile organics online monitoring system and the EMS system for one month in November 2011 in the northern suburb of Nanjing, and 56 VOC components and reactive gases (NO(x), CO and O3) were measured. The results showed that the VOC hourly averaged volume fraction in Nanjing northern suburb was about 48.17 x 10(-9), and the minimum value of VOCs occurred at 16:00. The diurnal variation showed a bimodal characteristic, indicating the significant impact of motor vehicle emission. The VOC concentration and O3 concentration exhibited negative correlation in the daytime. The average OH consumption rate of VOCs was approximately 3.26 x 10(-12) cm3 x (molecule x s)(-1), and the largest incremental reactivity was about 3.26 mol x mol(-1); Alkenes contributed the largest-parts of the OH consumption rate (L(OH)) and the ozone formation potential (OFP), followed by aromatics. Although alkanes were the most abundant components of VOCs in the atmosphere, it is not the main contributor of L(OH) and OFP. The key active components in VOCs were ethylene, propylene, 1-butene, m,p-xylene and isoprene, etc. The dominant factor of ozone formation was VOCs in this observation.
The objective of this research was to study the CYP2E1 gene expression in carbon tetrachloride (CCl4)-induced acute liver injury in hepatitis B virus (HBV) transgenic mice. Twenty-four HBV (-) and 24 HBV (+) transgenic mice aged 8 to 10 weeks were selected for the present study. Intraperitoneal injection of 1.0 ?L/g of CCl4 (1:4 dissolved in olive oil) to mice was performed to induce acute liver injury model. Eight normal clean-grade C57BL/6 mice were taken as the control group. The control group received saline intraperitoneally. The mice in each group were killed 3, 6, 12, 24, 48, and 72 h after injection. The liver tissue samples of mice were collected. The liver histological changes at different time points in each group were observed under light microscope. The quantitative PCR methods were utilized to measure the relative mRNA levels of CYP2E1 gene in liver tissues. Immunohistochemistry and Western blot techniques were used to observe tissue expression levels of CYP2E1 in each group. Compared with that of the control group, mRNA and protein expression levels of CYP2E1 significantly increased both in the HBV (-) group and in the HBV (+) group after the CCl4 induced the acute liver injury, and it reached the peak at 72 h after the CCl4 injection. Compared with the HBV (-) group, the mice in the HBV (+) group had severe liver damage and significantly increased CYP2E1 gene and protein expression levels. In the CCl4-induced acute liver injury of HBV transgenic mice, the CYP2E1 gene expression significantly increased. The results provided evidence for the HBV-induced liver damage and liver cancer pathogenesis.
To study the optimum preparation process and stability of beta-cyclodextrin inclusion compound in volatile oil of Cinnamomum longepaniculatum leaves. The saturated aqueous solution method was adopted to prepare inclusion compounds for an orthogonal test. The inclusion compound productivity and the inclusion rate were taken as indexes for screening the inclusion processes. The inclusion effect was evaluated with the infrared spectrophotometry and TLC, and the stability under conditions of high temperature, high humidity and strong light was detected. Under optimum preparation conditions for inclusion, the ratio between volatile oil and beta-cyclodextrin was 1: 8 (mL: g), that between beta-cyclodextrin and water was 1: 15, the inclusion temperature was 40 degrees C, and the inclusion time was 3 h. The results of spectrophotometry and TLC showed that the optimum conditions can generate beta-cyclodextrin inclusion compound in volatile oil of C. longepaniculatum leaves with certain light resistance, thermo-stability and hygro-stability. Therefore the optimum inclusion process features simple operation and stable inclusion compounds.
To investigate aberrant genome-wide CpG methylation patterns in cortex brain tissue of APP/PS1 mice and as compared to controls, which allows for identification of novel disease-associated genes. This study investigates the genome-wide DNA methylation profiles of the cortex from APP/PS1 transgenic mice and control mice using the Roche NimbleGen chip platform. Functional analysis was then conducted by Ingenuity Pathways Analysis system. The methylated DNA fragments in the genome of each sample were enriched by MeDIP and the whole-genome interrogations were hybridized to the Roche NimbleGen Human DNA Methylation 3x720 K CpG Island Plus RefSeq Promoter Array that cover 15,980 CpG islands and 20,404 reference gene promoter regions of the entire human genome. Analysis reveals 2346 CpG sites representing 485 unique genes as potentially associated with AD disease status pending confirmation in additional study. At the same time, these hyper-methylated genes display familial aggregation. An impairment of the transforming growth factor-?1 (TGF-?1) signaling pathway has been demonstrated to be specific to the AD brain and, particularly, to the early phase of the disease, supporting a role for epigenetic change of TGF-?1 in AD pathology. In future research, we will focus on TGF-?1, as it appeared to be the most promising candidate for AD.
A novel, highly sensitive electrochemical immunoassay was proposed for the simultaneous determination of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCCA) for the diagnosis of cervical cancer. Using an electrochemical analysis technique, two well-separated peaks were generated by neutral red and thionine, making the simultaneous detection of the two analytes on the electrode possible. Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), containing more amino groups, was of benefit to immobilize the primary antibody (Ab1) through an amidation reaction. Au@mesoporous carbon CMK-3 was synthesized and incubated with two secondary antibodies (Ab2) and different redox probes (neutral red and thionine) to fabricate the electrochemical immunosensor label intending to improve the analytical performance of the immunosensor. The immunosensor was prepared with a sandwich structure based on the peak current change of neutral red and thionine before and after the antigen-antibody reaction. The results showed that the immunosensor had a wide linear range, low detection limit, good reproducibility and stability. The method has been applied to the analysis of serum samples with satisfactory results.
Advanced neuroimaging approaches have been employed to prove that migraine was a central nervous system disorder. This study aims to examine resting-state abnormalities in migraine without aura (MWoA) patients stratified by disease duration, and to explore the neuroimaging markers for reflecting the disease duration.
In this paper, Pd nanoplates were used as a kind of electrode materials for fabrication of an electrochemical immunosensor, which was applied for detection of cancer biomarker alpha-fetoprotein (AFP). Thanks to the unique structure and properties of Pd nanoplates, the antibody of AFP (Ab) was effectively immobilized onto the surface of the Pd nanoplates modified glassy carbon electrode (GCE). Moreover, the good electrochemical properties of Pd nanoplates greatly improved the electronic transmission rate and enhanced the electrochemical signal, which led to an increase of the detection sensitivity. Based on the specific antibody-antigen interaction, a label-free immunosensor based on Pd nanoplates was developed for sensing of AFP. The current method allows us to detect AFP over a wide concentration range from 0.01 to 75.0ng/mL with a detection limit of 4pg/mL. The proposed immunosensor has been used to determine AFP in human serum with satisfactory results.
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