Alexandertimmons9096

A surface modification of nanoparticles (NPs) provides an effective way to control their interactions with living cells. The complete understanding of interactions between NPs and a cell membrane is a key step for the development of drug delivery. In the present work, the role of different surface charges (anionic, cationic, and zwitterionic) on the internalization through an idealized plasma membrane was investigated using a coarse-grained molecular dynamics (CGMD) technique. The decorated AuNPs used in this in silico study closely imitated those experimentally synthesized, while the idealized plasma membrane model resembled that found in living cells. The mechanism of direct translocation of a 2 nm particle by membrane was observed. The zwitterionic AuNP demonstrates a higher free-energy barrier than the positively and negatively charged AuNPs, resulting in a lack of preference for internalization across the membrane, leading to lower translocation rate and permeability of internalization. Despite the surface coverage, the agglomeration of AuNPs in a physiological condition has been observed resulting in slow unfavorable permeability. Our study highlights that in addition to surface charges, the hydrodynamic size (DH) plays an important role in the permeability of the functionalized AuNPs into the cell membrane. Through our simulations, complete understanding of interactions between ligands-coated AuNPs and the realistic plasma membrane has been established serving as a platform for the novel design of AuNPs in nanomedicine applications.The four glucosyl esters were synthesized and tested for the determination of infection enzyme leukocyte esterase (LE) in human synovial (joint) fluid and urine. The esters acted as LE substrates releasing glucose in a direct proportion to the activity of LE in a sample. The freed glucose was then detected by a coupled-enzyme assay at either a nitrogen-doped carbon nanotube (N-CNT) electrode or a commercial glucose test strip. The assays at the N-CNT electrode detected LE down to 0.81 nM (25 μg L-1) and showed the fastest kinetics (2.1 × 105 M-1 s-1) for esters with the least crowded space around their carbonyl group. When used with glucose strips, the esters discerned clinically relevant levels of LE up to at least 26 nM (800 μg L-1) in the microliter-sized samples of bodily fluids. 5-HT molecular weight The reading of glucose strips with a potentiostat, instead of a personal glucose meter (blood glucometer), shortened the time of required sample incubation from 3 h to 5 min. Correcting the signal of incubated sample for that of original sample eliminated matrix effects and accounted for the presence of native glucose. The new esters have a potential to extend the use of glucose strips (already used by millions for diabetes monitoring) to the quantification of the severity of urinary tract and periprosthetic joint infections.Electrochemical aptamer-based (E-AB) sensors achieve highly precise measurements of specific molecular targets in untreated biological fluids. This unique ability, together with their measurement frequency of seconds or faster, has enabled the real-time monitoring of drug pharmacokinetics in live animals with unprecedented temporal resolution. However, one important weakness of E-AB sensors is that their bioelectronic interface degrades upon continuous electrochemical interrogation-a process typically seen as a drop in faradaic and an increase in charging currents over time. This progressive degradation limits their in vivo operational life to 12 h at best, a period that is much shorter than the elimination half-life of the vast majority of drugs in humans. Thus, there is a critical need to develop novel E-AB interfaces that resist continuous electrochemical interrogation in biological fluids for prolonged periods. In response, our group is pursuing the development of better packed, more stable self-assembled monolayers (SAMs) to improve the signaling and extend the operational life of in vivo E-AB sensors from hours to days. By invoking hydrophobicity arguments, we have created SAMs that do not desorb from the electrode surface in aqueous physiological solutions and biological fluids. These SAMs, formed from 1-hexanethiol solutions, decrease the voltammetric charging currents of E-AB sensors by 3-fold relative to standard monolayers of 6-mercapto-1-hexanol, increase the total faradaic current, and alter the electron transfer kinetics of the platform. Moreover, the stability of our new SAMs enables uninterrupted, continuous E-AB interrogation for several days in biological fluids, like undiluted serum, at a physiological temperature of 37 °C.Room-temperature ionic liquids (RTILs) are synthetic electrolytes with electrochemical stability superior to that of conventional aqueous-based electrolytes, allowing a significantly enlarged electrochemical window for application as capacitors. In this study, we propose a variant of an existing RTIL model for solvent-free RTILs, accounting for both ion-ion correlations and nonelectrostatic interactions. Using this model, we explore the phenomenon of spontaneous surface charge separation in RTIL capacitors and find that this transition is a common feature for realistic choices of the model parameters in most RTILs. In addition, we investigate the effects of asymmetric preferential ion adsorption on this charge separation transition and find that proximity of the transition in this case can result in greatly enhanced energy storage. Our work suggests that differential chemical treatment of electrodes can be a simple and useful means for optimizing energy storage in RTIL capacitors.G protein-coupled receptors (GPCRs) are one of the most important drug targets, accounting for ∼34% of drugs on the market. For drug discovery, accurate modeling and explanation of bioactivities of ligands is critical for the screening and optimization of hit compounds. Homologous GPCRs are more likely to interact with chemically similar ligands, and they tend to share common binding modes with ligand molecules. The inclusion of homologous GPCRs in learning bioactivities of ligands potentially enhances the accuracy and interpretability of models due to utilizing increased training sample size and the existence of common ligand substructures that control bioactivities. Accurate modeling and interpretation of bioactivities of ligands by combining homologous GPCRs can be formulated as multitask learning with joint feature learning problem and naturally matched with the group lasso learning algorithm. Thus, we proposed a multitask regression learning with group lasso (MTR-GL) implemented by l2,1-norm regularization to model bioactivities of ligand molecules and then tested the algorithm on a series of thirty-five representative GPCRs datasets that cover nine subfamilies of human GPCRs. link2 The results show that MTR-GL is overall superior to single-task learning methods and classic multitask learning with joint feature learning methods. Moreover, MTR-GL achieves better performance than state-of-the-art deep multitask learning based methods of predicting ligand bioactivities on most datasets (31/35), where MTR-GL obtained an average improvement of 38% on correlation coefficient (r2) and 29% on root-mean-square error over the DeepNeuralNet-QSAR predictors.The highly diastereoselective 1,4-conjugate additions of several nitrogen nucleophiles to chiral bicyclic dehydroalanines have been assessed effectively at room temperature in good to excellent yields without needing any catalyst or additional base. This methodology is general, simple, oxygen and moisture tolerant, high-yielding, totally chemo- and stereoselective. This procedure offers an efficient and practical approach for the synthesis of Nβ-substituted α,β-diamino acids, such as 1-isohistidine, τ-histidinoalanine, β-benzylaminoalanine, β-(piperidin-1-yl)alanine, β-(azepan-1-yl)alanine, and fluorescent and ciprofloxacin-containing amino acid derivatives.Two-dimensional (2D) materials may enable a general approach to the introduction of a dipole at a semiconductor surface as well as control over other properties of the double layer at a semiconductor/liquid interface. Vastly different properties can be found in the 2D materials currently studied due in part to the range of the distribution of density-of-states. In this work, the open-circuit voltage (Voc) of p-Si-H, p-Si/Gr (graphene), and p-Si/h-BN (hexagonal boron nitride) in contact with a series of one-electron outer-sphere redox couples was investigated by macroscale measurements as well as by scanning electrochemical cell microscopy (SECCM). The band gaps of Gr and h-BN (0-5.97 eV) encompass the wide range of band gaps for 2D materials, so these interfaces (p-Si/Gr and p-Si/h-BN) serve as useful references to understand the behavior of 2D materials more generally. The value of Voc shifted with respect to the effective potential of the contacting solution, with slopes (ΔVoc/ΔEEff) of -0.27 and -0.38 for p-Si/Gr and p-Si/h-BN, respectively, indicating that band bending at the p-Si/h-BN and p-Si/Gr interfaces responds at least partially to changes in the electrochemical potential of the contacting liquid electrolyte. Additionally, SECCM is shown to be an effective method to interrogate the nanoscale photoelectrochemical behavior of an interface, showing little spatial variance over scales exceeding the grain size of the CVD-grown 2D materials in this work. The measurements demonstrated that the polycrystalline nature of the 2D materials had little effect on the results and confirmed that the macroscale measurements reflected the junction behavior at the nanoscale.As a biomaterial, silk presents unique features with a combination of excellent mechanical properties, biocompatibility, and biodegradability. link3 The biodegradability aspects of silk biomaterials, especially with options to control the rate from short (days) to long (years) time frames in vivo, make this protein-based biopolymer a good candidate for developing biodegradable devices used for tissue repairs and tissue engineering, as well as medical device implants. Silk materials, including native silk fibers and a broad spectrum of regenerated silk materials, have been investigated in vitro and in vivo to demonstrate degradation by proteolytic enzymes. In this Review, we summarize the findings on these studies on the enzymatic degradation of Bombyx mori (B. mori) silk materials. We also present a discussion on the factors that dictate the degradation properties of silk materials. Finally, in future perspectives, we highlight some key challenges and potential directions toward the future study of the degradation of silk materials.Palladium-catalyzed amination reactions using soluble organic bases have provided a solution to the many issues associated with heterogeneous reaction conditions. Still, homogeneous C-N cross-coupling approaches cannot yet employ bases as weak and economical as trialkylamines. Furthermore, organic base-mediated methods have not been developed for Ni(0/II) catalysis, despite some advantages of such systems over those employing Pd-based catalysts. We designed a new air-stable and easily prepared Ni(II) precatalyst bearing an electron-deficient bidentate phosphine ligand that enables the cross-coupling of aryl triflates with aryl amines using triethylamine (TEA) as base. The method is tolerant of sterically congested coupling partners, as well as those bearing base- and nucleophile-sensitive functional groups. With the aid of density functional theory (DFT) calculations, we determined that the electron-deficient auxiliary ligands decrease both the pKa of the Ni-bound amine and the barrier to reductive elimination from the resultant Ni(II)-amido complex.