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Castro Clemmensen posted an update 21 hours, 19 minutes ago
Comparison to neutral Pym-Wn clusters reveals the drastic effects of protonation on microhydration with respect to both structure and interaction strength.Cisplatin is a platinum-based chemotherapeutic agent widely used in the treatment of various solid tumors. However, a major challenge in the use of cisplatin and in the development of cisplatin derivatives, namely Pt(iv) prodrugs, is their premature reduction in the bloodstream before reaching cancer cells. To circumvent this problem, we designed liposomal nanoparticles coupled with a cholesterol-tethered amphiphilic Pt(iv) prodrug. The addition of cholesterol served to stabilize the formation of the liposome, while selectively incorporating cholesterol as the axial ligand also allowed the Pt(iv) prodrug to readily migrate into the liposomal bilayer. Notably, upon embedding into the nanoparticles, the Pt(iv) prodrug showed marked resistance against premature reduction in human plasma in vitro. Pharmacokinetic analysis in a mouse model also showed that the nanoparticles significantly extend the half-life of the Pt(iv) prodrug to 180 min, which represents a >6-fold increase compared to cisplatin. Importantly, such lipid modification did not compromise the genotoxicity of cisplatin, as the Pt(iv) prodrug induced DNA damage and apoptosis in ovarian cancer cell lines efficiently. Taken together, our strategy provides a novel insight as to how to stabilize a platinum-based compound to increase the circulation time in vivo, which is expected to enhance the efficacy of drug treatment.Tailoring the structures of nanomachines to achieve specific functions is one of the major challenges in chemistry. Disentangling the different movements of nanomachines is critical to characterize their functions. Here, the motions within one kind of molecular machine, a foldaxane, composed of a foldamer with a spring-like conformation on an axle have been examined at the molecular level. With the aid of molecular dynamics simulations and enhanced sampling methods, the free-energy landscape characterizing the shuttling of the foldaxane has been drawn. The calculated free-energy barrier, amounting to 20.7 kcal mol-1, is in good agreement with experiments. Further analysis reveals that the predominant contribution to the free-energy barrier stems from the disruption of the hydrogen bonds between the foldamer and the thread. In the absence of hydrogen bonding interactions between the terminals of the foldamer and the thread, shrinkage and swelling movements of the foldamer have been identified and investigated in detail. By deciphering the intricate mechanism of how the foldaxane shuttles, our understanding of motions within molecular machines is expected to be improved, which will, in turn, assist the construction of molecular machines with specific functions.Nanobodies are antigen binding variable domains of heavy-chain antibodies without light-chains, and these biomolecules occur naturally in the serum of Camelidae species. Nanobodies have a compact structure and low molecular weight when compared with antibodies, and are the smallest active antigen-binding fragments. Because of their remarkable stability and manipulable characteristics, nanobodies have been incorporated into biomaterials and used as molecular recognition and tracing agents, drug delivery systems, molecular imaging tools and disease therapeutics. This review summarizes recent progress in this field focusing on nanobodies as versatile biomolecules for biomedical applications.Here, a continuous two-step glass-capillary microfluidic technique to produce a multistage oral delivery system is reported. Insulin is successfully encapsulated into liposomes, which are coated with chitosan to improve their mucoadhesion. The encapsulation in an enteric polymer offers protection from the harsh gastric conditions. Insulin permeability is enhanced across an intestinal monolayer.As environmental pollution and energy shortages have become global concerns, the construction of highly efficient catalysts using facile and green methods remains a long-term goal. In the present study, we proposed a facile catalyst preparation method in which Ag/TiO2 composites were coated on the surface of the porous pure inorganic crystalline vanadium phosphates (VPO) by a one-step strategy. More importantly, the in situ reduction of Ag nanoparticles was achieved at room temperature without severe conditions or hydrogen atmosphere in which the porous VPO was employed as the reductant. The prepared Ag/VPO@TiO2 composites act as a class of efficient bifunctional catalysts for visible light photodegradation of MB molecules and catalytic reduction of p-nitrophenol (4-NP). Among these samples, the 6.82%Ag/VPO@TiO2 composite exhibited a superior photocatalytic activity in the degradation of MB and an ultrafast reduction rate for 4-NP of about 0.1 mM/40 s. The photocatalytic mechanistic studies revealed that the encapsulated VPO with a narrow band gap not only efficiently enhances the photosensitivity of the TiO2 but also largely facilitates the photogenerated charge separation. The subsequent deposition of Ag NPs is able to further promote electron transfer ability, which leads to the higher photocatalytic activity. Moreover, the contact of Ag NPs with the surface of semiconductor TiO2 can result in an electron-enhanced area in their interface that could effectively facilitate the uptake of electrons by the 4-NP molecules and then improve the reduction activity.Biomimetic hydrogels have emerged as the most useful tissue engineering scaffold materials. Their versatile chemistry can recapitulate multiple physical and chemical features to integrate cells, scaffolds, and signaling molecules for tissue regeneration. Due to their highly hydrophilic nature hydrogels can recreate nutrient-rich aqueous environments for cells. read more Soluble regulatory molecules can be incorporated to guide cell proliferation and differentiation. Importantly, the controlled dynamic parameters and spatial distribution of chemical cues in hydrogel scaffolds are critical for cell-cell communication, cell-scaffold interaction, and morphogenesis. Herein, we review biomimetic hydrogels that provide cells with spatiotemporally controlled chemical cues as tissue engineering scaffolds. Specifically, hydrogels with temporally controlled growth factor-release abilities, spatially controlled conjugated bioactive molecules/motifs, and targeting delivery and reload properties for tissue engineering applications are discussed in detail.