RESUMO
The design of an efficient electrocatalyst for effective trace level determinations of noxious synthetic and or biological compounds is the unceasingly noteworthy conceptual approach for rapid technology. In this work, we designed a magnesium-aluminum layered double hydroxides (Mg-Al LDHs) nanocatalyst and applied it to the electrocatalytic determination of an extremely carcinogenic catechol sensor. A coprecipitation method was employed for synthesizing the nanocatalyst, and the structure, porous nature, and morphology were confirmed by X-ray diffraction, Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherm, field emission-scanning electron microscopy, and transmission electron microscopy. The elemental composition was observed by energy dispersive X-ray analysis. The electrochemical studies were investigated with the help of cyclic voltammetry and differential pulse voltammetry techniques. The Mg-Al LDHs-based electrocatalyst was used to detect catechol by electrochemical measurements with different parameters. The proposed catechol sensor shows a wide dynamic range (0.007-200 µM) with a lower level of detection (2.3 nm) and sensitivity (3.57 µA µM-1 cm-2). The excellent sensor performance is attributed to the high surface area, fast electron transfer, more active sites, and excellent flexibility. This study depicts the proposed sensor as probable to practical in a scientific investigation. In addition, the modified electrode showed greater selectivity and was used in the detection of fatal contaminants in instant treatment strategies. Moreover, the Mg-Al LDHs confirmed auspicious real sample scrutiny with noteworthy retrieval outcomes in lake water samples which exposed improved consequences.
Assuntos
Alumínio , Técnicas Eletroquímicas , Catecóis , Técnicas Eletroquímicas/métodos , Hidróxidos , Limite de Detecção , MagnésioRESUMO
Current tumor immunotherapy approaches include the genetic modification of peripheral T cells to express tumor antigen-specific T-cell receptors (TCRs). The approach, tested in melanoma, has led to some limited success of tumor regression in patients. Yet, the introduction of exogenous TCRs into mature T cells entails an underlying risk; the generation of autoreactive clones due to potential TCR mispairing, and the lack of effective negative selection, as these peripheral cells do not undergo thymic selection following introduction of the exogenous TCR. We have successfully generated MART-1-specific CD8 T cells from genetically modified human hematopoietic stem cells (hHSC) in a humanized mouse model. The advantages of this approach include a long-term source of antigen specific T cells and proper T-cell selection due to thymopoiesis following expression of the TCR. In this report, we examine the molecular processes occurring on endogenous TCR expression and demonstrate that this approach results in exclusive cell surface expression of the newly introduced TCR, and the exclusion of endogenous TCR cell surface expression. This suggests that this stem cell based approach can provide a potentially safer approach for anticancer immunotherapy due to the involvement of thymic selection.
Assuntos
Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/imunologia , Seleção Clonal Mediada por Antígeno/imunologia , Expressão Gênica , Rearranjo Gênico do Linfócito T , Células-Tronco Hematopoéticas/citologia , Humanos , Implantes Experimentais , Camundongos , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , TransgenesRESUMO
Inhibiting the expression of the HIV-1 coreceptor CCR5 holds great promise for controlling HIV-1 infection in patients. Here we report stable knockdown of human CCR5 by a short hairpin RNA (shRNA) in a humanized bone marrow/liver/thymus (BLT) mouse model. We delivered a potent shRNA against CCR5 into human fetal liver-derived CD34(+) hematopoietic progenitor/stem cells (HPSCs) by lentiviral vector transduction. We transplanted vector-transduced HPSCs solidified with Matrigel and a thymus segment under the mouse kidney capsule. Vector-transduced autologous CD34(+) cells were subsequently injected in the irradiated mouse, intended to create systemic reconstitution. CCR5 expression was down-regulated in human T cells and monocytes/macrophages in systemic lymphoid tissues, including gut-associated lymphoid tissue, the major site of HIV-1 replication. The shRNA-mediated CCR5 knockdown had no apparent adverse effects on T-cell development as assessed by polyclonal T-cell receptor Vbeta family development and naive/memory T-cell differentiation. CCR5 knockdown in the secondary transplanted mice suggested the potential of long-term hematopoietic reconstitution by the shRNA-transduced HPSCs. CCR5 tropic HIV-1 infection was effectively inhibited in mouse-derived human splenocytes ex vivo. These results demonstrate that lentiviral vector delivery of shRNA into human HPSCs could stably down-regulate CCR5 in systemic lymphoid organs in vivo.
Assuntos
Medula Óssea/metabolismo , Infecções por HIV/metabolismo , HIV-1 , Transplante de Células-Tronco Hematopoéticas , Fígado/metabolismo , Receptores CCR5/biossíntese , Timo/metabolismo , Animais , Diferenciação Celular/genética , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Infecções por HIV/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Memória Imunológica/genética , Lentivirus , Camundongos , Camundongos Endogâmicos NOD , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores CCR5/genética , Linfócitos T/metabolismo , Transdução Genética , Transplante HeterólogoRESUMO
In this work, we designed tetragonal nanogravel structured dysprosium vanadate Dy(VO4) nanoparticles unified with oxidized carbon nanofiber (f-CNF) denoted as Dy(VO4)/f-CNF nanocomposite for the low potential determination of antiprotozoal drug metronidazole (MEZ). The physicochemical properties of novel Dy(VO4)/f-CNF nanocomposite were analyzed through microscopic and spectroscopic techniques and obtained results express nanocomposite formed with desired surface morphology, crystalline phase, atomic vibrational modes, and preferred elemental compositions. The electrocatalytic activity of Dy(VO4)/f-CNF nanocomposite was examined with a disposable screen-printed electrode (SPCE) via cyclic voltammetry (CV) and linear sweep voltammetry technique (LSV) with a conventional three-electrode system. Dy(VO4)/f-CNF/SPCE delivers a higher active surface area recommends superior electrocatalytic activity which is favorable for the MEZ sensor. Electrocatalytic reduction of MEZ occurred with lower reduction potential (-0.55 V) with dynamic linear range (1.5-1036.9 µM), lower detection limit (6 nm), LOQ (0.022 µM), and higher sensitivity (1.12 µA µM-1 cm2). The anti-interference studies retain its actual current without any shift in cathodic potential. Besides, the practical feasibility outcomes with higher cathodic current with the higher recovery rate and RSD in human blood sample, urine sample, and lake water as a real samples. Thus, Dy(VO4)/f-CNF nanocomposite modified SPCE considers being a potential candidate for the MEZ sensor.
Assuntos
Nanofibras , Preparações Farmacêuticas , Carbono , Disprósio , Técnicas Eletroquímicas , Eletrodos , Humanos , Metronidazol , VanadatosRESUMO
The innovation of novel and proficient nanostructured materials for the precise level determination of pharmaceuticals in biological fluids is quite crucial to the researchers. With this in mind, we synthesized iron molybdate nanoplates (Fe2(MoO4)3; FeMo NPs) via simple ultrasonic-assisted technique (70 kHz with a power of 100 W). The FeMo NPs were used as the efficient electrocatalyst for electrochemical oxidation of first-generation antihistamine drug- Promethazine hydrochloride (PMH). The as-synthesized FeMo NPs were characterized and confirmed by various characterization techniques such as XRD, Raman, FT-IR, FE-SEM, EDX and Elemental mapping analysis and electron impedance spectroscopy (EIS). In addition, the electrochemical characteristic features of FeMo NPs were scrutinized by electrochemical techniques like cyclic voltammetry (CV) and differential pulse voltammetry technique (DPV). Interestingly, the developed FeMo NPs modified glassy carbon electrode (FeMo NPs/GCE) discloses higher peak current with lesser anodic potential on comparing to bare GCE including wider linear range (0.01-68.65 µM), lower detection limit (0.01 µM) and greater sensitivity (0.97 µAµM-1cm-2). Moreover, the as-synthesized FeMo NPs applied for selectivity, reproducibility, repeatability and storage ability to investigate the practical viability. In the presence of interfering species like cationic, anionic and biological samples, the oxidation peak current response doesn't cause any variation results disclose good selectivity towards the detection of PMH. Additionally, the practical feasibility of the FeMo NPs/GCE was tested by real samples like, commercial tablet (Phenergan 25 mg Tablets) and lake water samples which give satisfactory recovery results. All the above consequences made clear that the proposed sensor FeMo NPs/GCE exhibits excellent electrochemical behavior for electrochemical determination towards oxidation of antihistamine drug PMH.
Assuntos
Carbono/química , Eletroquímica/instrumentação , Antagonistas dos Receptores Histamínicos/análise , Ferro/química , Molibdênio/química , Nanoestruturas/química , Prometazina/análise , Sonicação , Técnicas de Química Sintética , Eletrodos , Vidro/química , Antagonistas dos Receptores Histamínicos/sangue , Antagonistas dos Receptores Histamínicos/urina , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Prometazina/sangue , Prometazina/urina , TemperaturaRESUMO
Design of Pt alloy catalysts with enhanced activity and durability is a key challenge for polymer electrolyte membrane fuel cells. In the present work, we compare the durability of the ordered intermetallic face-centered tetragonal (fct) PtFeCu catalyst for the oxygen reduction reaction (ORR) relative to its counterpart bimetallic catalysts, i.e., the ordered intermetallic fct-PtFe catalyst and the commercial catalyst from Tanaka Kikinzoku Kogyo, TKK-PtC. Although both fct catalysts initially exhibited an ordered structure and mass activity approximately 2.5 times higher than that of TKK-Pt/C, the presence of Cu at the ordered intermetallic fct-PtFeCu catalyst led to a significant enhancement in durability compared to that of the ordered intermetallic fct-PtFe catalyst. The ordered intermetallic fct-PtFeCu catalyst retained more than 70% of its mass activity and electrochemically active surface area (ECSA) over 10â¯000 durability cycles carried out at 60 °C. In contrast, the ordered intermetallic fct-PtFe catalyst maintained only about 40% of its activity. The temperature of the durability experiment is also shown to be important: the catalyst was more severely degraded at 60 °C than at room temperature. To obtain insight into the observed enhancement in durability of fct-PtFeCu catalyst, a postmortem analysis of the ordered intermetallic fct-PtFeCu catalyst was carried out using scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX) line scan. The STEM-EDX line scans of the ordered intermetallic fct-PtFeCu catalyst over 10â¯000 durability cycles showed a smaller degree of Fe and Cu dissolution from the catalyst. Conversely, large dissolution of Fe was identified in the ordered intermetallic fct-PtFe catalyst, indicating a lesser retention of Fe that causes the destruction of ordered structure and gives rise to poor durability. The enhancement in the durability of the ordered intermetallic fct-PtFeCu catalyst is ascribed to the synergistic effects of Cu presence and the ordered structure of catalyst.