Tafamidis stabilizes the tetramer by forming H-bond with S52 in the flexible CD loop to increase its structural stability. Despite the strong binding affinity of tafamidis, the free-energy surface constructed from metadynamics simulation suggests that tafamidis unbinds more readily than AG10 with lower free-energy barriers between the binding state and other intermediates. Finally, by performing pharmacophore analysis, we found two common important moieties of the studied compounds for their binding on the pockets, which can provide valuable guidance for future lead compounds' optimization in designing drugs for ATTR amyloidosis.Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both in vitro and in vivo results demonstrated that the obtained O2@PFOB@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of O2@PFOB@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the O2@PFOB@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.Advanced understanding of Alzheimer's disease (AD) and several tauopathies over the past decades indicates the pathological importance of tau aggregation in these diseases. Herein, we demonstrated that adenosine triphosphate (ATP), a highly charged anionic molecule found abundantly in the cytosol of cells, catalyzes fibrillation of tau as well as human islet amyloid polypeptide, a representative of basic intrinsically disordered proteins. Our results showed that ATP attracts multiple lysine residues of the four-repeat domain of tau (K18) via supramolecular complexation, thereby forming dimers that are converted to nuclei and accelerate fibril elongation. However, ATP was not directly incorporated into the K18 fibrils, suggesting that ATP plays the role of a catalyst, rather than a reactant, during K18 fibrillation. We also characterized the correlation between ATP dyshomeostasis and tau aggregation in the cellular environment. Our multiple biophysical approaches, including native mass spectrometry (MS), small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulation, provided insights into the molecular-level influence of ATP on the structural changes and fibrillation of tau.The molecular catalyst sensitized system (MCSS), where an excited molecular catalyst adsorbed on a semiconductor such as TiO2 injects electrons to the conduction band of the semiconductor leading to hydrogen evolution/CO2 reduction coupled with an oxidation of water on the molecular catalyst, has been one of the most probable candidates in the approach to artificial photosynthesis. For a full utilization of visible light, however, a serious light scattering of the aqueous suspension of TiO2 in the visible region, which is generally experienced, should be avoided. Here, we report a preparation of optically transparent colloidal dispersion of TiO2 by the sol/gel reaction of TiCl4 through progressive hydrolysis/condensation under the basic condition without any calcination processes. The TiO2 nanoparticles (TiO2(NPs)) obtained were characterized as an amorphous particle (∼10-15 nm) having a microcrystal domain of anatase within several nm by XRD, Raman spectroscopies, XRF, XAFS, TG/DTA, and HRTEM, respectively. nhanced hydrophilicity upon UV light irradiation.Silicon is regarded as one of the most promising next generation lithium-ion battery anodes due to its exceptional theoretical capacity, appropriate voltage profile, and vast abundance. Nevertheless, huge volume expansion and drastic stress generated upon lithiation cause poor cyclic stability. It has been one of the central issues to improve cyclic performance of silicon-based lithium-ion battery anodes. Constructing hierarchical macro-/mesoporous silicon with a tunable pore size and wall thickness is developed to tackle this issue. Rational structure design, controllable synthesis, and theoretical mechanical simulation are combined together to reveal fundamental mechanisms responsible for an improved cyclic performance. A self-templating strategy is applied using Stöber silica particles as a templating agent and precursor coupled with a magnesiothermic reduction process. Systematic variation of the magnesiothermic reduction time allows good control over the structures of the porous silicon. Finite element mechanical simulations on the porous silicon show that an increased pore size and a reduced wall thickness generate less mechanical stress in average along with an extended lithiation state. Besides the mechanical stress, the evolution of strain and displacement of the porous silicon is also elaborated with the finite element simulation.Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1-42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1-42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1-42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1-42) tetramer and are in agreement with a 21 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1-42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.MicroRNA existing in exosomes (exo-miRNA) is a crucial and reliable biomarker for cancer screening and diagnosis. However, accurate detection of ultralow exo-miRNA amounts in real samples remains a challenge. Herein, a robust and ultrasensitive electrochemical biosensor was developed based on localized DNA cascade displacement reaction (L-DCDR) and versatile DNA nanosheets (DNSs) for enzyme-free analysis of exo-miRNA. The target activated L-DCDR repeatedly by consecutive toehold-mediated strand displacement, which released plentiful P strands to hybridize with capture probes immobilized on the electrode surface and DNS tags, generating an amplified electrochemical signal for the detection of exo-miRNA. https://www.selleckchem.com/products/lipopolysaccharides.html The DNS could label-free load various electroactive molecules. The electrochemical biosensor revealed high sensitivity ranging from 0.1 fM to 1 nM with a limit of detection of 65 aM and good specificity. The constructed biosensor was demonstrated to be able to detect exo-miRNA derived from gastric

cancer cell line (SGC-7901) and gastric cancer patients. In addition, the developed biosensor possessed several considerable advantages including simple substrate assembly, improved reaction rate, and high signal-to-noise ratio. Therefore, this strategy has great potential in bioanalysis and clinical diagnostics.High-entropy oxides (HEOs) have attracted increasing interest owing to their unique structures and fascinating physicochemical properties. Spherical mesoporous HEOs further inherit the advantages of spherical mesoporous materials including high surface area and tunable pore size. However, it is still a huge challenge to construct HEOs with uniform spheres and a mesoporous framework. Herein, a wet-chemistry sol-gel strategy is demonstrated for the synthesis of spherical mesoporous HEOs (e.g., Ni-Co-Cr-Fe-Mn oxide) with high specific surface area (42-143 m2/g), large pore size (5.5-8.3 nm), unique spherical morphology (∼55 nm), and spinel structure without any impure crystal phase using polyphenol as a polymerizable ligand. The metal/polyphenol-formaldehyde resin colloidal spheres are first synthesized via a sol-gel process. Because of their abundant catechol groups and strong chelating ability with different metal species, polyphenols can not only accommodate five different metal ions in their networks but also be well polymerized by formaldehyde to form colloidal spheres. After calcination, the metal species aggregate together to form HEOs, while the organic resin is fully decomposed to produce mesopores. Because of the open framework with accessible mesopores, they could be used as a peroxymonosulfate catalyst for degradation of organic pollutants and a nanoplatform for efficient detection of DNA. This work demonstrates a straightforward sol-gel strategy for design and synthesis of spherical mesoporous high-entropy materials, which would promote the exploration of new properties of high-entropy materials and extend their application.Red blood cell death or erythrocyte apoptosis (eryptosis) is generally mediated by oxidative stress, energy depletion, heavy metals exposure, or xenobiotics. As erythrocytes are a major target for oxidative stress due to their primary function as O2-carrying cells, they possess an efficient antioxidant defense system consisting of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and peroxiredoxin 2 (Prx2). The oxidative stress-mediated activation of the Ca2+-permeable cation channel results in Ca2+ entry into the cells and subsequent cell death. Herein, we describe for the first time that selenium compounds having intramolecular diselenide or selenenyl sulfide moieties can prevent the oxidative stress-induced eryptosis by exhibiting an unusual Prx2-like redox activity under conditions when the cellular Prx2 and CAT enzymes are inhibited.Re-entrant geometries can effectively trap air pockets beneath coating surfaces, prevent the penetration of low surface tension organic liquids, and achieve superamphiphobic performance. However, the creation of re-entrant geometries through particle-based spray coating remains a challenge. In the past decade, various studies have focused on the preparation of superamphiphobic coatings using ultrafine nanoparticles (10-15 nm) using conventional spray-coating methods. In this work, we aim to fabricate a spray-coated superamphiphobic surface using large particles with a hierarchical structure. The study systematically investigated the wetting behaviors of liquids with different topographies obtained using large particles (i.e., smooth, micro, nano, and micro/nanostructures) by different coating methods. The findings suggested that compared with the typical colloid template method, the surface obtained using the spray-coating method showed much greater roughness, which greatly enhanced the oleophobicity of the coating.
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