Ultrasensitive Electrochemical Biosensor Based on Efficient PDA-APDMAO Antifouling Interface and Dual-Signal Ratio Strategy for Trace Detection of Alpha-Fetoprotein in Human Serum.

In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N+-O-) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/m). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.

Identification of efficient amine transaminase and applicability in dual transaminases cascade for synthesis of L-phosphinothricin.

L-phosphinothricin (L-PPT) is the most popular broad-spectrum and highly effective herbicide. Transaminases (TAs) play a pivotal role in asymmetric synthesis of L-PPT, yet encounter the challenge of unfavorable reaction equilibrium. In this study, the novel dual transaminases cascade system (DTCS) was introduced to facilitate the synthesis of L-PPT. The specific amine transaminase BdATA, originating from Bradyrhizobium diazoefficiens ZJY088, was screened and identified. It exhibited remarkable activity, good stability, and required only 2.5 equivalents of isopropylamine to transform pyruvate effectively. By coupling BdATA with previously reported SeTA to construct the DTCS for pyruvate removal in situ, the L-PPT yield escalated from 37.37 % to 85.35 %. Three advantages of the DTCS were presented: the removal of pyruvate alleviated by-product inhibition, the use of isopropylamine reduced reliance on excess L-alanine, and no demand for expensive cofactors like NAD(P)H. It demonstrated an innovative idea for addressing the challenges associated with transaminase-mediated synthesis of L-PPT.

Small Charged Molecule-Mediated Fibrillar Mineralization: Implications for Ectopic Calcification.

Numerous small biomolecules exist in the human body and play roles in various biological and pathological processes. Small molecules are believed not to induce intrafibrillar mineralization alone. They are required to work in synergy with noncollagenous proteins (NCPs) and their analogs, e.g. polyelectrolytes, for inducing intrafibrillar mineralization, as the polymer-induced liquid-like precursor (PILP) process has been well-documented. In this study, we demonstrate that small charged molecules alone, such as sodium tripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane, could directly mediate fibrillar mineralization. We propose that small charged molecules might be immobilized in collagen fibrils to form the polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds. The PLCC could attract CaP precursors along with calcium and phosphate ions for inducing mineralization without any polyelectrolyte additives. The small charged molecule-mediated mineralization process was evidenced by Cryo-TEM, AFM, SEM, FTIR, ICP-OES, etc., as the PLCC exhibited both characteristic features of collagen fibrils and polyelectrolyte with increased charges, hydrophilicity, and density. This might hint at one mechanism of pathological biomineralization, especially for understanding the ectopic calcification process.

Promoting neurovascularized bone regeneration with a novel 3D printed inorganic-organic magnesium silicate/PLA composite scaffold.

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10% A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Amino modified nanofibers anchored to Prussian blue nanoparticles selectively remove Cs+ from water.

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.

Synthesis of aminopropyl triethoxysilane/melamine incorporated superhydrophilic membranes for simultaneous removal of oil, metals, and Salt ions from produced water.

Water treatment has turned out to be more important in most societies due to the expansion of most economies and to advancement of industrialization. Developing efficient materials and technologies for water treatment is of high interest. Thin film nanocomposite membranes are regarded as the most effective membranes available for salts, hydrocarbon, and environmental pollutants removal. These membranes improve productivity while using less energy than conventional asymmetric membranes. Here, the polyvinylidene fluoride (PVDF) membranes have been successfully modified via dip single-step coating by silica-aminopropyl triethoxysilane/trimesic acid/melamine nanocomposite (Si-APTES-TA-MM). The developed membranes were evaluated for separating the emulsified oil/water mixture, the surface wettability of the membrane materials is therefore essential. During the conditioning step, that is when the freshwater was introduced, the prepared membrane reached a flux of about 27.77 L m-2 h-1. However, when the contaminated water was introduced, the flux reached 18 L m-2 h-1, alongside an applied pressure of 400 kPa. Interestingly, during the first 8 h of the filtration test, the membrane showed 90 % rejection for ions including Mg2+, and SO42- and ≈100 % for organic pollutants including pentane, isooctane, toluene, and hexadecane. Also, the membrane showed 98 % rejection for heavy metals including strontium, lead, and cobalt ions. As per the results, the membrane could be recommended as a promising candidate to be used for a mixture of salt ions, hydrocarbons, and mixtures of heavy metals from wastewater.

Targeted doxorubicin-loaded core-shell copper peroxide-mesoporous silica nanoparticles for combination of ferroptosis and chemotherapy of metastatic breast cancer.

In the current study, a tumor microenvironment responsive (TME-responsive) copper peroxide-mesoporous silica core-shell structure with H2O2 self-supplying ability was fabricated for targeted ferroptosis/chemotherapy against metastatic breast cancer. At the first stage, copper peroxide nanodot was synthesized and subsequently coated with mesoporous organosilica shell. After (3-Aminopropyl) triethoxysilane (APTMS) functionalization of the organosilica shell, doxorubicin (DOX) was loaded in the mesoporous structure of the nanoparticles and then, heterofunctional COOH-PEG-Maleimide was decorated on the surface through EDC/NHS chemistry. Afterward, thiol-functionalized AS1411 aptamer was conjugated to the maleimide groups of the PEGylated nanoparticles. In vitro study illustrated ROS generation of the system in the treated 4 T1 cell. Cellular uptake and cytotoxicity experiments showed enhanced internalization and cytotoxicity of the targeted system comparing to non-targeted one. The in vivo study on ectopic 4 T1 tumor induced in Female BALB/c mice showed ideal therapeutic effect of Apt-PEG-Silica-DOT@DOX with approximately 90 % tumor suppression in comparison with 50 % and 25 % tumor suppression for PEG-Silica-DOT@DOX and PEG-Silica-DOT. Moreover, Apt-PEG-Silica-DOT@DOX provide favorable characteristics for biosafety issues concerning the rate of survival and loss of body weight. The prepared platform could serve as a multifunctional system with smart behavior in drug release, tumor accumulation and capable for ferroptosis/chemotherapy against breast cancer.

Improvement of interface bonding of bacterial cellulose reinforced aged paper by amino-silanization.

The aging of paper seriously threatens the service life of cultural heritage documents. Bacterial cellulose (BC), which has a good fiber aspect ratio and is rich in hydroxyl groups, is suitable for strengthening aged paper. However, a single BC added was not ideal for paper restoration, since only strengthening was not able to resist the persistent acidification of ancient book. In this work, BC was functionalized by 3-aminopropyltriethoxysilane (APTES) to develop the interface bonding with aged paper. Fourier transform infrared (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and elemental analysis identified the successful amino-silanization of BC. The modification parameters were optimized as the concentration of APTES of 5 wt%, the reaction time of 4 h, and the reaction temperature of 80 °C based on a considerable improvement in the strength properties without obvious appearance impact on reinforced papers. Moreover, the pH value of the repaired paper was achieved at 8.03, ensuring the stability of the anti-aging effect. The results confirmed that APTES-BC had great potential applications in ancient books conservation.

Enhancing the strength and toughness of polylactic acid-based composites through one-step co-deposition of active coating onto wood fiber.

A facial strategy of co-deposition is proposed to enhance the interfacial bonding in wood fiber (WF)/polylactic acid (PLA) composites. Dopamine or tannic acid (TA) was co-deposited with 3-aminopropyltriethoxysilane (APTES) onto the WF surface to create active coatings. These coatings were formed through Michael addition and Schiff base reactions and effectively attached to the WF through a combination of hydrogen and covalent bonding. Such active coatings facilitated the connection between WF and PLA through both covalent bonds and physical entanglements, thereby enhancing the interfacial interactions and compatibility between the two components. The co-deposition of TA with APTES was found to be more effective than with dopamine, leading to a dramatic improvement in the tensile strength and elongation at break of the composites by 33.4 % and 185.9 %, respectively. This work offers a facile method to prepare high performance plant fiber reinforced PLA composites, thereby broadening the potential applications of PLA.

Novel hydrogel pillar array based ratiometric multicolor fluorescence biosensor for visual detection of alkaline phosphatase activity.

Enzyme-induced in-situ fluorescence is crucial for the development of biosensing mechanisms and correlative spectroscopic analysis. Inspired by simple p-aminophenol (AP)-controlled synthesis and the specific catalytic reaction of 4-aminophenyl phosphate (APP) triggered by alkaline phosphatase (ALP), our research proposed a strategy to prepare carbon dots (CDs) as fluorescent signals for ALP detection using AP and 3-aminopropyltrimethoxysilane (APTMS) as the precursors. The further constructed ratiometric fluorescence sensor reduced the detection limit of ALP to 0.075 µU/mL by a significant margin. Considering the need for point-of-care testing (POCT), we chose agarose for the preparation of portable hydrogel sensors so that even untrained personnel can quickly achieve semi-quantitative visual detection of ALP using colorimetric cards. These results demonstrate the practical applicability of ratiometric fluorescence sensing hydrogel pillar arrays, which are important for high-sensitivity, visualization, and portable rapid enzyme activity assays.

Are Terminal Alkynes Necessary for MAO-A/MAO-B Inhibition? A New Scaffold Is Revealed.

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski's rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson's disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.

Folic acid-mediated enhancement of the diagnostic potential of luminescent europium-doped hydroxyapatite nanocrystals for cancer biomaging.

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

Propitious catalytic response of immobilized α-amylase from G. thermoleovorans in modified APTES-Fe3O4 NPs for industrial bio-processing.

Challenges in enzyme and product recovery are currently intriguing in modern biotechnology. Coping enzyme stability, shelf life and efficiency, nanomaterials-based immobilization were epitomized of industrial practice. Herein, a α-amylase from Geobacillus thermoleovorans was purified and bound effectively on to a modified 3-Aminopropyltriethoxysilane (APTES)-Fe3O4 nanoparticle. It was revealed that the carrier-bound enzyme catalysis (pH 8 and 60 °C) was significant in contrast to the free enzyme (pH 7.5 and 55 °C). Furthermore, Zn2+ and Cu2+ were shown to cause inhibitory effects in both enzyme states. Unlike chloroform, toluene, benzene, and butanol, minimal effects were observed with ethanol, acetone, and hexane. The bound enzyme retained 27.4 % of its initial activity after being stored for 36 days. In addition, the reusability of the bound enzyme showed a gradual decline in activity after the first cycle; however, after 13 cycles, its residual activity at 53 % was observed. These data proved significant enough to use this enzyme for industrial starch and analogous substrate bio-processing.

Sea urchin nanostructured nickel cobaltite modified carbon cloth integrated wearable patches for the on-site detection of the immunosuppressant drug mycophenolate mofetil.

Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCo2O4) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCo2O4. The enhanced activity of NiCo2O4 was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCo2O4 was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCo2O4 was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 µM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.

Shadow electrochemiluminescence imaging of giant liposomes opening at polarized electrodes.

In this work, the release of giant liposome (∼100 µm in diameter) content was imaged by shadow electrochemiluminescence (ECL) microscopy. Giant unilamellar liposomes were pre-loaded with a sucrose solution and allowed to sediment at an ITO electrode surface immersed in a solution containing a luminophore ([Ru(bpy)3]2+) and a sacrificial co-reactant (tri-n-propylamine). Upon polarization, the electrode exhibited illumination over its entire surface thanks to the oxidation of ECL reagents. However, as soon as liposomes reached the electrode surface, dark spots appeared and then spread over time on the surface. This observation reflected a blockage of the electrode surface at the contact point between the liposome and the electrode surface, followed by the dilution of ECL reagents after the rupture of the liposome membrane and release of its internal ECL-inactive solution. Interestingly, ECL reappeared in areas where it initially faded, indicating back-diffusion of ECL reagents towards the previously diluted area and thus confirming liposome permeabilization. The whole process was analyzed qualitatively and quantitatively within the defined region of interest. Two mass transport regimes were identified: a gravity-driven spreading process when the liposome releases its content leading to ECL vanishing and a diffusive regime when ECL recovers. The reported shadow ECL microscopy should find promising applications for the imaging of transient events such as molecular species released by artificial or biological vesicles.

Antimicrobial and hydrophobic cellulose paper prepared by covalently attaching cinnamaldehyde for strawberries preservation.

The demand for paper-based packaging materials as an alternative to incumbent disposable petroleum-derived polymers for food packaging applications is ever-growing. However, typical paper-based formats are not suitable for use in unconventional applications due to inherent limitations (e.g., excessive hydrophilicity, lack antimicrobial ability), and accordingly, enabling new capabilities is necessity. Herein, a simple and environmentally friendly strategy was proposed to introduce antimicrobial and hydrophobic functions to cellulose paper through successive chemical grafting of 3-aminopropyltriethoxysilane (APS) and cinnamaldehyde (CA). The results revealed that cellulose paper not only showed long-term antibacterial effect on different bacteria, but also inhibited a wide range of fungi. Encouragingly, the modified paper, which is fluorine-free, displays a high contact angle of 119.7°. Thus, even in the wet state, the modified paper can still maintain good mechanical strength. Meanwhile, the multifunctional composite papers have excellent biocompatibility and biodegradability. Compared with ordinary cellulose paper, multifunctional composite paper can effectively prolong the shelf life of strawberries. Therefore, the multifunctional composite paper represents good application potential as a fruit packaging material.

Generalized Multifunctional Coating Strategies Based on Polyphenol-Amine-Inspired Chemistry and Layer-by-Layer Deposition for Blood Contact Catheters.

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.

Detection of tetanus toxoid with iron magnetic nanobioprobe.

Diagnosis of diseases with low facilities, speed, accuracy and sensitivity is an important matter in treatment. Bioprobes based on iron oxide nanoparticles are a good candidate for early detection of deadly and infectious diseases such as tetanus due to their high reactivity, biocompatibility, low production cost and sample separation under a magnetic field. In this study, silane groups were coated on surface of iron oxide nanoparticles using tetraethoxysilane (TEOS) hydrolysis. Also, NH2groups were generated on the surface of silanized nanoparticles using 3-aminopropyl triethoxy silane (APTES). Antibody was immobilized on the surface of silanized nanoparticles using TCT trichlorothriazine as activator. Silanization and stabilized antibody were investigated by using of FT-IR, EDX, VSM, SRB technique. UV/vis spectroscopy, fluorescence, agglutination test and ELISA were used for biosensor performance and specificity. The results of FT-IR spectroscopy showed that Si-O-Si and Si-O-Fe bonds and TCT chlorine and amine groups of tetanus anti-toxoid antibodies were formed on the surface of iron oxide nanoparticles. The presence of Si, N and C elements in EDX analysis confirms the silanization of iron oxide nanoparticles. VSM results showed that the amount of magnetic nanoparticles after conjugation is sufficient for biological applications. Antibody stabilization on nanoparticles increased the adsorption intensity in the uv/vis spectrometer. The fluorescence intensity of nano bioprobe increased in the presence of 10 ng ml-1. Nanobio probes were observed as agglomerates in the presence of tetanus toxoid antigen. The presence of tetanus antigen caused the formation of antigen-nanobioprobe antigen complex. Identification of this complex by HRP-bound antibody confirmed the specificity of nanobioprobe. Tetanus magnetic nanobioprobe with a diagnostic limit of 10 ng ml-1of tetanus antigen in a short time can be a good tool in LOC devices and microfluidic chips.

Drugs possessing aryloxypropanamine pharmacophore, duloxetine, dapoxetine and propranolol, increase allopregnanolone in rat brain: Possible involvement of allopregnanolone in their central nervous system effects.

Allopregnanolone (AP) is a neurosteroid synthesized in the brain and a positive allosteric modulator of γ-aminobutyric acid (GABA) type A receptors. Some drugs possessing the aryloxypropanamine (AOPA) pharmacophore, such as fluoxetine, exert their central nervous system (CNS) effects by increasing the brain AP. Although duloxetine (DLX), dapoxetine (DPX), atomoxetine (ATX) and propranolol (PRL) also possess the AOPA pharmacophore and are used to treat some psychiatric disorders, the capabilities of these drugs to increase the brain AP and the possible involvement of AP in their CNS effects remain to be fully elucidated. To clarify these points, we first developed a method for quantifying AP in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry. Analysis of the changes in the brain AP levels using this method revealed that the intraperitoneal administration of DLX (10 mg/kg), DPX (10 mg/kg) and PRL (20 mg/kg) significantly increased the brain AP (DLX: < 0.40-2.74 ng/g tissue, DPX: 1.48-3.83 ng/g tissue and PRL: < 0.40-2.09 ng/g tissue) compared to the saline administration (<0.40 ng/g tissue). These results suggested the possible involvement of the GABAergic neurosteroid, AP, in the central actions of DLX, DPX and PRL. In contrast, ATX (10 mg/kg) did not affect the AP levels in the brain. In addition, the brain and serum AP levels had a remarkably high positive correlation after the administration of DLX, DPX and PRL. Thus, this study proposed the AP-related novel mechanism of actions of DLX, DPX and PRL in the CNS.