Enzymes play a pivotal role in regulating numerous bodily functions. Thus, there is a growing need for developing sensors enabling real-time monitoring of enzymatic activity and inhibition. The activity and inhibition of cholinesterase (CHE) enzymes in blood plasma are fluorometrically monitored using near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) as probes, strategically functionalized with myristoylcholine (MC)– the substrate of CHE. A significant decrease in the fluorescence intensity of MC-suspended SWCNTs upon interaction with CHE is observed, attributed to the hydrolysis of the MC corona phase of the SWCNTs by CHE. Complementary measurements for quantifying choline, the product of MC hydrolysis, reveal a correlation between the fluorescence intensity decrease and the amount of released choline, rendering the SWCNTs optical sensors with real-time feedback in the NIR biologically transparent spectral range. Moreover, when synthetic and naturally abundant inhibitors inhibit the CHE enzymes present in blood plasma, no significant modulations of the MC-SWCNT fluorescence are observed, allowing effective detection of CHE inhibition. The rationally designed SWCNT sensors platform for monitoring of enzymatic activity and inhibition in clinically relevant samples is envisioned to not only advance the field of clinical diagnostics but also deepen further understanding of enzyme-related processes in complex biological fluids. 相似文献
A chemoselective S‐arylation reaction of thio‐oxindoles with arynes is presented. The reaction was performed under mild conditions and provided a straightforward synthesis of 2‐(arylthio)indolenines in good to excellent yields. Besides, this simple operational protocol is not only scalable but also has good functional group compatibilities and substrate scope. Thus, our protocol should allow for the expansion of chemical space via developing new scaffolds of thioimidates that are difficult to synthesize otherwise.
Understanding the targeted cellular uptake of nanomaterials is an essential step to engineer and program functional and effective biomedical devices. In this respect, the targeting and ultrafast uptake of zeolite nanocrystals functionalized with Cetuximab antibodies (Ctxb) by cells overexpressing the epidermal growth factor receptor are described here. Biochemical assays show that the cellular uptake of the bioconjugate in the targeted cancer cells already begins 15 min after incubation, at a rate around tenfold faster than that observed in the negative control cells. These findings further show the role of Ctxb exposed at the surfaces of the zeolite nanocrystals in mediating the targeted and rapid cellular uptake. By using temperature and pharmacological inhibitors as modulators of the internalization pathways, the results univocally suggest a dissipative uptake mechanism of these nanomaterials, which seems to occur using different internalization pathways, according to the targeting properties of these nanocrystals. Owing to the ultrafast uptake process, harmless for the cell viability, these results further pave the way for the design of novel theranostic tools based on nanozeolites. 相似文献
In the reversed field pinch (RFP), plasmas exhibit various self-organized states. Among these, the three-dimensional (3D) helical state known as the “quasi-single-helical” (QSH) state enhances RFP confinement. However, accurately describing the equilibrium is challenging due to the presence of 3D structures, magnetic islands, and chaotic regions. It is difficult to obtain a balance between the available diagnostic and the real equilibrium structure. To address this issue, we introduce KTX3DFit, a new 3D equilibrium reconstruction code specifically designed for the Keda Torus eXperiment (KTX) RFP. KTX3DFit utilizes the stepped-pressure equilibrium code (SPEC) to compute 3D equilibria and uses polarimetric interferometer signals from experiments. KTX3DFit is able to reconstruct equilibria in various states, including axisymmetric, double-axis helical (DAx), and single-helical-axis (SHAx) states. Notably, this study marks the first integration of the SPEC code with internal magnetic field data for equilibrium reconstruction and could be used for other 3D configurations. 相似文献
The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient’s macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis. 相似文献
Polymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco-friendly polyurethane using lignin, a sustainable bio-polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro-2a cell models demonstrated the non-cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications. 相似文献
This paper numerically investigated the mechanisms of powder de-agglomeration on mechanical impaction, aiming to explain the experimental observations in our previous study (Adi et al., 2010). A numerical model based on a coupled computational fluid dynamics (CFD) and discrete element method (DEM) approach was developed to simulate the dispersion of drug mannitol agglomerates in the customised impaction throats containing one or two angles with different flow rates. Information in terms of particle-throat and particle-fluid interactions, number of fragments, fine particle fraction (FPF) and powder deposition was monitored over the whole process and quantitatively analysed. The results indicated that the breakage of the agglomerate was mainly attributed to the mechanical impaction and less affected by the shear effect from the flow-particle interaction. While the first impaction caused the major damage to the agglomerate, the second impaction in fact generated more fine particles with size less than 5 μm, resulting much improved dispersion performance for the throats with two angles. Powder deposition, which is dependent on impaction velocity and angle and fragment size, was another important factor affecting the dispersion. The analysis of dispersion mechanisms indicated that de-agglomeration at different conditions can be characterised by the ratio of the particle-wall impaction energy and agglomerate strength. 相似文献
Wireless Personal Communications - The concept of connected devices is effectively integrated to create heterogeneous wireless networks like the Internet of Things (IoT). These networks are using... 相似文献
