Daughertywesth2054

Two paralogs of the guanine dissociation inhibitor-like solubilizing factors UNC119, UNC119A and UNC119B, are present in the human genome. UNC119 binds to N-myristoylated proteins and masks the hydrophobic lipid from the hydrophilic cytosol, facilitating trafficking between different membranes. Two classes of UNC119 cargo proteins have been classified low affinity cargoes, released by the Arf-like proteins ARL2 and ARL3, and high affinity cargoes, which are specifically released by ARL3 and trafficked to either the primary cilium or the immunological synapse. The UNC119 homologues have reported differences in functionality, but the structural and biochemical bases for these differences are unknown. Using myristoylated peptide binding and release assays, we show that peptides sharing the previously identified UNC119A high affinity motif show significant variations of binding affinities to UNC119B of up to 427-fold. Furthermore, we solve the first two crystal structures of UNC119B, one in complex with the high affinity cargo peptide of LCK and a second one in complex with the release factor ARL3. Using these novel structures, we identify a stretch of negatively charged amino acids unique to UNC119B that may undergo a conformational change following binding of a release factor which we propose as an additional release mechanism specific to UNC119B.Mechanical stability and multicycle durability are essential for emerging solid sorbents to maintain an efficient CO2 adsorption capacity and reduce cost. In this work, a strong foam-like composite is developed as a CO2 sorbent by the in situ growth of thermally stable and microporous metal-organic frameworks (MOFs) in a mesoporous cellulose template derived from balsa wood, which is delignified by using sodium chlorite and further functionalized by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation. The surface carboxyl groups in the TEMPO-oxidized wood template (TO-wood) facilitate the coordination of the cellulose network with multivalent metal ions and thus enable the nucleation and in situ growth of MOFs including copper benzene-1,3,5-tricarboxylate [Cu3(BTC)2], zinc 2-methylimidazolate, and aluminum benzene-1,3,5-tricarboxylate. The TO-wood/Cu3(BTC)2 composite shows a high specific surface area of 471 m2 g-1 and a high CO2 adsorption capacity of 1.46 mmol g-1 at 25 °C and atmospheric pressure. It also demonstrates high durability during the temperature swing cyclic CO2 adsorption/desorption test. In addition, the TO-wood/Cu3(BTC)2 composite is lightweight but exceptionally strong with a specific elastic modulus of 3034 kN m kg-1 and a specific yield strength of 68 kN m kg-1 under the compression test. The strong and durable TO-wood/MOF composites can potentially be used as a solid sorbent for CO2 capture, and their application can possibly be extended to environmental remediation, gas separation and purification, insulation, and catalysis.Here, we investigate competitive adsorption and photocatalytic reaction over TiO2@SiO2 NO conversion efficiency decreases by 29.1%, and the adsorption capacity decreases from 0.125 to 0.095 mmol/g due to the influence of SO2. According to identification and comparative analysis of the IR signal, SO2 has little effect on the NO conversion route and intermediates (adsorbed NO → nitrite → nitrate), but accelerates the deactivation of catalysts. The electronic interaction scheme from density functional theory (DFT) confirms that surface hydroxyls create an unsaturated coordination of neighboring Ti or O atoms, which is favorable for NO/SO2 adsorption on anatase (101). Chitosan oligosaccharide In addition, the lone pair electrons of N or S atoms prefer to be delocalized and form covalent bonds with active surface-O on the (101) facet with terminal hydroxyls. However, preadsorbed SO2 could offset the increase of hydroxyls and strongly inhibit NO adsorption, which is consistent with the result performance evaluation. A possible reaction mechanism characterized by oxygen vacancies and·O2- is proposed, while the essential reason of catalyst deactivation and regeneration is theoretically analyzed based on the experimental and DFT calculation.Mitochondrial drug delivery has attracted increasing attention in various mitochondrial dysfunction-associated disorders such as cancer owing to the important role of energy production. Herein, we report a lysosomal pH-activated mitochondrial-targeting polymer nanoparticle to overcome drug resistance by a synergy between mitochondrial delivery of doxorubicin (DOX, an anticancer drug) and erlotinib-mediated inhibition of drug efflux. The obtained nanoparticles, DE-NPs could maintain negative charge and have long blood circulation while undergoing charge reversal at lysosomal pH after internalization by cancer cells. Thereafter, the acidity-activated polycationic and hydrophobic polypeptide domains boost lysosomal escape and mitochondrial-targeting drug delivery, leading to mitochondrial dysfunction, ATP suppression, and cell apoptosis. Moreover, the suppressed ATP supply and erlotinib enabled dual inhibition of drug efflux by DOX-resistant MCF-7/ADR cells, leading to significantly augmented intracellular DOX accumulation and a synergistic anticancer effect with a 17-fold decrease of IC50 relative to DOX. In vivo antitumor study demonstrates that DE-NPs efficiently suppressed the tumor burden in MCF-7/ADR tumor-bearing mice and led to negligible toxicity. This work establishes that a combination of mitochondrial drug delivery and drug efflux inhibition could be a promising strategy for combating multidrug resistance.Nucleic acids are regarded as reliable biomarkers for the early diagnosis of various diseases. By ingeniously combining a transduction hairpin (THP) with the toehold-mediated strand displacement reaction (TSDR) to form three-leg DNAzyme walkers, for the first time, we constructed a label-free and sensitive electrochemical sensing system for the amplification detection of target nucleic acids. With microRNA-155 (miR-155) as a model target, the feasibility of the biosensing strategy and the conformational states of DNA in the recognition process were studied in detail on the basis of electrochemical and dual polarization interferometry techniques. With the assistance of THP, miR-155 indirectly triggered the TSDR between three hairpins (H1, H2, and H3), then massive Mg2+-dependent three-leg DNAzyme walkers were formed in aqueous solutions. After the binding/cleaving/moving process of three-leg DNAzyme walkers on the electrode surface modified with substrate hairpins (SHPs), a number of single-stranded DNAs (ssDNAs) were generated.