Zhouwaller5808

There are two important topics in the field of cancer research one is targeted molecular therapy and the other is tumor molecular imaging. Focal adhesion kinase (FAK) is considered as an attractive target for oncologic diagnosis and therapy. A series of 2,4-diaminopyrimidine derivatives were labeled with 18F to study their biological properties and their potential as positron emission tomography tumor imaging agents. They inhibited the activity of FAK with IC50 values in the wide range of 0.6-2164 nM, among which the IC50 of Q6 was 3.2 nM. For the biodistribution in S180-bearing mice, the corresponding [18F]Q6 was relatively good, with the highest uptake of 3.35 ± 0.32 % ID/g at 30 min postinjection, with a tumor/muscle ratio of 2.08 and a tumor/bone ratio of 2.48. Accordingly, [18F]Q6 was considered as a potential PET imaging agent for tumor diagnosis.All-atom molecular dynamics simulations of the 10 nm-sized anionic polystyrene (PS) particle complexed with plasma proteins (human serum albumin, immunoglobulin gamma-1 chain-C, and apolipoprotein A-I) adsorbed onto lipid bilayers [asymmetrically composed of extracellular (zwitterionic) and cytosolic (anionic) leaflets] are performed. Free energies calculated from umbrella sampling simulations show that proteins on the particle more weakly bind to the zwitterionic leaflet than do bare particles, in agreement with experiments showing the suppression of the particle-bilayer binding by protein corona. Proteins on the particle interact more strongly with the anionic leaflet than with the zwitterionic leaflet because of charge interactions between cationic protein residues and anionic lipid headgroups, to an extent dependent on various plasma proteins. In particular, hydrogen bonds between proteins and zwitterionic leaflets restrict the motion of lipids and thus reduce the lateral dynamics of bilayers, while the tight binding between proteins and anionic leaflets disrupts the helical structure of proteins and disorders lipids, leading to an increase in the lateral dynamics of bilayers. These findings help explain the experimental observation regarding the fact that the bilayer dynamics decreases when interacting with protein corona and suggest that the effect of protein corona on the binding strength and bilayer dynamics depends on protein types and bilayer charges.Computational high-throughput screening using molecular simulations is a powerful tool for identifying top-performing metal-organic frameworks (MOFs) for gas storage and separation applications. Accurate partial atomic charges are often required to model the electrostatic interactions between the MOF and the adsorbate, especially when the adsorption involves molecules with dipole or quadrupole moments such as water and CO2. Although ab initio methods can be used to calculate accurate partial atomic charges, these methods are impractical for screening large material databases because of the high computational cost. We developed a random forest machine learning model to predict the partial atomic charges in MOFs using a small yet meaningful set of features that represent both the elemental properties and the local environment of each atom. The model was trained and tested on a collection of about 320 000 density-derived electrostatic and chemical (DDEC) atomic charges calculated on a subset of the Computation-Ready Experimental Metal-Organic Framework (CoRE MOF-2019) database and separately on charge model 5 (CM5) charges. The model predicts accurate atomic charges for MOFs at a fraction of the computational cost of periodic density functional theory (DFT) and is found to be transferable to other porous molecular crystals and zeolites. A strong correlation is observed between the partial atomic charge and the average electronegativity difference between the central atom and its bonded neighbors.Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic indexes (TIs) of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive synthesis and optimization. Here, using bromodomain and extra-terminal (BET) protein inhibitors (BETi)-a class of epigenetic regulators with proven anticancer potential but clinical development hindered in large part by narrow TIs-we introduce a macromolecular prodrug platform that overcomes these challenges. Through tuning of traceless linkers appended to a "bottlebrush prodrug" scaffold, we demonstrate correlation of in vitro prodrug activation kinetics with in vivo tumor pharmacokinetics, enabling the predictive design of novel BETi prodrugs with enhanced antitumor efficacies and devoid of dose-limiting toxicities in a syngeneic triple-negative breast cancer murine model. This work may have immediate clinical implications, introducing a platform for predictive prodrug design and potentially overcoming hurdles in drug development.The ternary van der Waals material Nb2Six-1Te4 demonstrates many interesting properties as the content of Si is changed, ranging from metallic Nb3SiTe6 (x = 5/3) to narrow-gap semiconductor Nb2SiTe4 (x = 2) and with the emergence of one-dimensional Dirac fermion excitations in between. An in-depth understanding of their properties with different stoichiometry is important. Here we use scanning tunneling microscopy and spectroscopy to reveal that Nb2Six-1Te4 is a system with spontaneously developed and self-aligned one-dimensional metallic chains embedded in a two-dimensional semiconductor. Electron quasiparticles form one- and two-dimensional standing waves side by side. This special microscopic structure results in strong transport anisotropy. Along the chain direction the material behaves like a metal, while perpendicular to the chain direction, it behaves like a semiconductor. These findings provide an important basis for further investigation of this intriguing system.Naked-eye-visible color/graphical patterns have shown significant potential in optical encryption. However, current strategies for optical encryption are usually based on static or homogeneous information, which limits their applications in multivalue coding and advanced confidential encryption. Here, we propose a concept of spatiotemporally tunable optical encryption by constructing a multilevel binary-color spatial heterojunction pattern into the time dimension. This multiple coding strategy can enable a simple pattern much more difficult to be counterfeited and keep the facile authentication by naked eyes or smartphone at the same time. As a proof of concept, we fabricated a moving red-green heterojunction pattern by elaborately utilizing the directional swelling process of a poly(dimethylsiloxane) matrix in organic solvents and the ion-exchange property of a perovskite quantum dot wrapped in it. We demonstrate that trioctylphosphine plays a significant role in endowing the red-green heterojunction with a stable and distinct interface for better perception by eyes. The directional swelling and following ion-exchange dynamics in the local interface indicate that we can tailor the movement of the binary-color heterojunction in a quasi-continuous way via orthogonal variables of swelling ratio and ion concentration gradient. Silmitasertib in vitro The concept of heterojunction-based multivalue optical encryption in the time dimension is independent with other dimensions, indicating a promising compatibility with the existing optical encryption systems.DNA nanotechnology has seen large developments over the last 30 years through the combination of solid phase synthesis and the discovery of DNA nanostructures. Solid phase synthesis has facilitated the availability of short DNA sequences and the expansion of the DNA toolbox to increase the chemical functionalities afforded on DNA, which in turn enabled the conception and synthesis of sophisticated and complex 2D and 3D nanostructures. In parallel, polymer science has developed several polymerization approaches to build di- and triblock copolymers bearing hydrophilic, hydrophobic, and amphiphilic properties. By bringing together these two emerging technologies, complementary properties of both materials have been explored; for example, the synthesis of amphiphilic DNA-polymer conjugates has enabled the production of several nanostructures, such as spherical and rod-like micelles. Through both the DNA and polymer parts, stimuli-responsiveness can be instilled. Nanostructures have consequently been developed with responsive structural changes to physical properties, such as pH and temperature, as well as short DNA through competitive complementary binding. These responsive changes have enabled the application of DNA-polymer conjugates in biomedical applications including drug delivery. This review discusses the progress of DNA-polymer conjugates, exploring the synthetic routes and state-of-the-art applications afforded through the combination of nucleic acids and synthetic polymers.Covalent organic frameworks (COFs) have great application potentials in photocatalytic water treatment. By using p-phenylenediamine with different numbers and locations of heterocyclic nitrogen atoms as a precursor, five types of COFs with different nitrogen positions were synthesized. We found that Cr(VI) photoreduction,Escherichia coli inactivation, and paracetamol degradation by COFs were heterocyclic nitrogen location-dependent. Particularly, the photocatalytic performance for all three tested pollutants by five types of COFs followed the order of the best performance for COF-PDZ with two ortho position heterocyclic N atoms, medium for COF-PMD with two meta position heterocyclic N atoms, and COF-PZ with two para position heterocyclic N atoms, and COF-PD with a single heterocyclic N atom, the worst performance for COF-1 without a heterocyclic N atom. Compared to the other COFs, COF-PDZ contained improved quantum efficiency and thus enhanced generation of electrons. The lower energy barriers and larger energy gaps of COF-PDZ contributed to its improved quantum efficiencies. The stronger affinity to Cr(VI) with lower adsorption energy of COF-PDZ also contributed to its excellent Cr(VI) reduction performance. By transferring into a more stable keto form, COF-PDZ showed great stability through five regeneration and reuse cycles. Overall, this study provided an insight into the synthesis of high-performance structure-dependent COF-based photocatalysts.The current syntheses of spheres-on-sphere (SOS) microsphere, which possesses both hollow cavity and hierarchical structure, mainly rely on complicated routes and template removal. In this study, a one pot nanoengineering strategy inspired by the automatic transport behavior of water in plants is successfully developed to fabricate SOS microsphere in tandem with a traditional soft template method in the preparation of hollow structure. Amphiphilic siloxane oligomers generated in situ from methyltriethoxylsilane (MTES) under acidic conditions are anchored on the surface of soft template St monomer droplets, sequentially completing hydrolysis-polycondensation and forming a mesoporous polysilsesquioxane (PSQ) shell. Then, the St monomers located in cavity migrate outward under the combined action of capillary force stemming from mesoporous and osmotic pressure generating from inside-outside of the PSQ shell and polymerize on the outside of the hollow PSQ shell, in which residual siloxane oligomers further anchor on the polystyrene (PS) surface to reduce the surface energy of the system, finally resulting in the successful formation of SOS particles.