Fosterhovmand0675

A pharmacokinetic evaluation in rats revealed that PTX NC@lipid-PEG-FA significantly prolonged the circulation of PTX in the bloodstream, in comparison with PTX NC or Taxol. Tissue distribution and in vivo antitumor studies in 4T1 orthotopic breast cancer-bearing nude mice showed that PTX NC@lipid-PEG-FA significantly increased the intratumor accumulation of PTX and efficiently inhibited tumor growth, in comparison with PTX NC@lipid-PEG, PTX NC, or Taxol. In summary, PTX NC@lipid-PEG-FA showed good potential for breast cancer-targeted delivery for insoluble therapeutics.Optical signals come from coherences between quantum states, with spectral line widths determined by the coherences' dephasing dynamics. Using a 2D electronic spectrometer, we observe weak coherence- and rephasing-time-domain signals persisting to 1 ps in the Fenna-Matthews-Olson complex at 77 K. These are coherences between the ground and excited states prepared after the complex interacts once or three times with light, rather than zero-quantum coherences that are more frequently investigated following two interactions. Here, we use these small but persistent signal components to isolate spectral contributions with narrowed peaks and reveal the system's eigenenergies.Both nitroreductase and the folate receptor are highly expressed in hypoxic tumors. The folate receptor is a potential target for tumors, and nitroreductase can selectively turn on the fluorescence of probes by reducing the nitro group to an amino group. Karan et al. (Karana, S., Cho, M., Lee, H., Lee, H., Park, H., Sundararajan, M., Sessler, J., and Hong, K. Near-infrared fluorescent probe activated by nitroreductase for in vitro and in vivo hypoxic tumor detection. J. Med. Chem. 2021) developed a near-infrared fluorescent probe for hypoxia tumor imaging analysis in vitro and in vivo using folate as the targeting site. This promising strategy may promote advances in precision diagnosis and treatment models of malignant tumors. This Viewpoint looks ahead to new possibilities rendered by their studies.A variety of enhanced statistical and numerical methods are now routinely used to extract important thermodynamic and kinetic information from the vast amount of complex, high-dimensional data obtained from molecular simulations. For the characterization of kinetic properties, Markov state models, in which the long-time statistical dynamics of a system is approximated by a Markov chain on a discrete partition of configuration space, have seen widespread use in recent years. However, obtaining kinetic properties for molecular systems with high energy barriers remains challenging as often enhanced sampling techniques are required with biased simulations to observe the relevant rare events. Particularly, the calculation of diffusion coefficients remains elusive from biased molecular simulation data. Here, we propose a novel method that can calculate multidimensional position-dependent diffusion coefficients equally from either biased or unbiased simulations using the same formalism. Our method builds on Markov state model analysis and the Kramers-Moyal expansion. We demonstrate the validity of our formalism using one- and two-dimensional analytic potentials and also apply it to data from explicit solvent molecular dynamics simulations, including the water-mediated conformations of alanine dipeptide and umbrella sampling simulations of drug transport across a lipid bilayer. Importantly, the developed algorithm presents significant improvement compared to standard methods when the transport of solute across three-dimensional heterogeneous porous media is studied, for example, the prediction of membrane permeation of drug molecules.The fate and transport of bacteria in porous media are essential for bioremediation and water quality control. However, the influence of biological activities like extracellular electron transfer (EET) and swimming motility toward granular media on cell transport remains unknown. Here, electroactive bacteria with higher Fe(III) reduction abilities were found to demonstrate greater retention in ferrihydrite-coated sand. Increasing the concentrations of the electron donor (1-10 mM lactate), shuttle (0-50 μM anthraquinone-2,6-disulfonate), and acceptor (ferrihydrite, MnO2, or biochar) under flow conditions significantly reduced Shewanella oneidensis MR-1's mobility through redox-active porous media. The deficiency of EET ability or flagellar motion and inhibition of intracellular proton motive force, all of which are essential for energy taxis, enhanced MR-1's transport. It was proposed that EET could facilitate MR-1 to sense, tactically move toward, and attach on redox-active media surface, eventually improving its retention. Positive linear correlations were established among parameters describing MR-1's energy taxis ability (relative taxis index), cell transport behavior (dispersion coefficient and relative change of effluent percentage), and redox activity of media surface (reduction potential or electron-accepting rate), providing novel insights into the critical impacts of bacterial microscale motility on macroscale cell transport through porous media.Conformational changes of proteins upon ligand binding are usually explained in terms of several mechanisms including the induced fit, conformational selection, or their mixtures. Due to the slow time scales, conventional molecular dynamics (cMD) simulations based on the atomistic models cannot easily simulate the open-to-closed conformational transition in proteins. In our previous study, we have developed an enhanced sampling scheme (generalized replica exchange with solute tempering selected surface charged residues gREST_SSCR) for multidomain proteins and applied it to ligand-mediated conformational changes in the G134R mutant of ribose-binding protein (RBPG134R) in solution. The free-energy landscape (FEL) of RBPG134R in the presence of a ribose at the binding site included the open and closed states and two intermediates, open-like and closed-like forms. Only the open and open-like forms existed in the FEL without a ribose. In the current study, the coupling between the conformational changes and ligand binding is further investigated using coarse-grained MD, multiple atomistic cMD, and free-energy calculations. The ribose is easily dissociated from the binding site of wild-type RBP and RBPG134R in the cMD simulations starting from the open and open-like forms. In contrast, it is stable at the binding site in the simulations from the closed and closed-like forms. The free-energy calculations provide the binding affinities of different structures, supporting the results of cMD simulations. Importantly, cMD simulations from the closed-like structures reveal transitions toward the closed one in the presence of a bound ribose. On the basis of the computational results, we propose a molecular mechanism in which conformational selection and induced fit happen in the first and second halves of the open-to-closed transition in RBP, respectively.Warfarin is a potent anti-coagulant drug and is on the World Health Organization's List of Essential Medicines. Additionally, it displays fluorescence enhancement upon binding to human serum albumin, making warfarin a prototype fluorescent probe in biology. Despite its biological significance, the current structural assignment of warfarin in aqueous solution is based on indirect evidence in organic solvents. Warfarin is known to exist in different isomeric forms-open-chain, hemiketal, and anionic forms-based on the solvent and pH. Moreover, warfarin displays a dual absorption feature in several solvents, which has been employed to study the ring-chain isomerism between its open-chain and hemiketal isomers. In this study, our pH-dependent experiments on warfarin and structurally constrained warfarin derivatives in aqueous solution demonstrate that the structural assignment of warfarin solely on the basis of its absorption spectrum is erroneous. Using a combination of steady-state and time-resolved spectroscopic experiments, along with quantum chemical calculations, we assign the observed dual absorption to two distinct π → π* transitions in the 4-hydroxycoumarin moiety of warfarin. Furthermore, we unambiguously identify the isomeric form of warfarin that binds to human serum albumin in aqueous buffer.Capsella bursa-pastoris (L.) Medik. has evolved resistance to ALS-inhibiting herbicides on a large scale. Previous studies primarily focused on the target-site resistance (TSR), and the non-TSR (NTSR) is not well characterized. In this study, pre-treatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion clearly reduced the tribenuron-methyl resistance in the resistant (R) population. After tribenuron-methyl treatment, the glutathione S-transferase (GST) activity of R plants was significantly higher than that of susceptible (S) plants. The higher tribenuron-methyl metabolism in R plants was also confirmed by using LC-MS/MS analysis. Bleomycin ic50 Isoform sequencing (Iso-Seq) combined with RNA sequencing (RNA-Seq) was used to identify candidate genes involved in non-target metabolic resistance in this population. A total of 37 differentially expressed genes were identified, 11 of them constitutively upregulated in R plants, including three P450s, one GST, two glycosyltransferases, two ATP-binding cassette transporters, one oxidase, and two peroxidases. This study confirmed the metabolic tribenuron-methyl resistance in C. bursa-pastoris, and the transcriptome data obtained by Iso-Seq combined with RNA-Seq provide gene resources for understanding the molecular mechanism of NTSR in C. bursa-pastoris.Main-group metal calcium-mediated alkylpyridine benzylic C(sp3)-H activation and functionalization have been achieved. The reaction of a calcium hydride complex [(DIPPnacnac)CaH(thf)2] (DIPPnacnac = CH(CMe)(2,6-iPr2-C6H3N)2) with two equivalents of 2,6-lutidine rapidly yields a monomeric calcium alkyl complex with the release of dihydrogen. A hydride/carbon-bridged binuclear calcium complex [(DIPPnacnac)Ca2(μ-H)2-Me-6-(μ-CH2)-Py(thf)] is obtained from an equimolar treatment of calcium hydride and 2,6-lutidine that is readily converted into mono- or binuclear calcium alkyl complexes upon subsequent addition of 2,6-lutidine. DFT calculations and kinetic studies are conducted to determine their reaction profiles. More significantly, this calcium hydride complex catalyzes regioselective benzylic C-H bond addition of alkylpyridines to a variety of alkenes, affording linear or branched alkylated pyridine derivatives.A novel porous polydimethylsiloxane (PDMS)-based capacitive pressure sensor was fabricated by optimizing the dielectric layer porosity for wide-range pressure sensing applications in the sports field. The pressure sensor consists of a porous PDMS dielectric layer and two fabric-based conductive electrodes. The porous PDMS dielectric layer was fabricated by introducing nitric acid (HNO3) into a mixture of PDMS and sodium hydrogen bicarbonate (NaHCO3) to facilitate the liberation of carbon dioxide (CO2) gas, which induces the creation of porous microstructures within the PDMS dielectric layer. Nine different pressure sensors (PS1, PS2,..., PS9) were fabricated in which the porosity (pore size, thickness) and dielectric constant of the PDMS dielectric layers were varied by changing the curing temperature, the mixing proportions of the HNO3/PDMS concentration, and the PDMS mixing ratio. The response of the fabricated pressure sensors was investigated for the applied pressures ranging from 0 to 1000 kPa. A relative capacitance change of ∼100, ∼323, and ∼485% was obtained by increasing the curing temperature from 110 to 140 to 170 °C, respectively.