Zhoubrantley4891

Synthetic nanopores made from DNA replicate the key biological processes of transporting molecular cargo across lipid bilayers. Understanding transport across the confined lumen of the nanopores is of fundamental interest and of relevance to their rational design for biotechnological applications. Here we reveal the transport principles of organic molecules through DNA nanopores by synergistically combining experiments and computer simulations. Using a highly parallel nanostructured platform, we synchronously measure the kinetic flux across hundreds of individual pores to obtain rate constants. The single-channel transport kinetics are close to the theoretical maximum, while selectivity is determined by the interplay of cargo charge and size, the pores' sterics and electrostatics, and the composition of the surrounding lipid bilayer. The narrow distribution of transport rates implies a high structural homogeneity of DNA nanopores. The molecular passageway through the nanopore is elucidated via coarse-grained constant-velocity steered molecular dynamics simulations. The ensemble simulations pinpoint with high resolution and statistical validity the selectivity filter within the channel lumen and determine the energetic factors governing transport. Our findings on these synthetic pores' structure-function relationship will serve to guide their rational engineering to tailor transport selectivity for cell biological research, sensing, and drug delivery.The host-guest chemistry of metal-organic nanocages is typically driven by thermodynamically favorable interactions with their guests such that uptake and release of guests can be controlled by switching this affinity on or off. Herein, we achieve this effect by reducing porphyrin-walled cationic nanoprisms 1a12+ and 1b12+ to zwitterionic states that rapidly uptake organometallic cations Cp*2Co+ and Cp2Co+, respectively. Cp*2Co+ binds strongly (Ka = 1.3 × 103 M-1) in the neutral state 1a0 of host 1a12+, which has its three porphyrin walls doubly reduced and its six (bipy)Pt2+ linkers singly reduced (bipy = 2,2'-bipyridine). https://www.selleckchem.com/products/erastin.html The less-reduced states of the host 1a3+ and 1a9+ also bind Cp*2Co+, though with lower affinities. link2 The smaller Cp2Co+ cation binds strongly (Ka = 1.7 × 103 M-1) in the 3e- reduced state 1b9+ of the (tmeda)Pt2+-linked host 1b12+ (tmeda = N,N,N',N'-tetramethylethylenediamine). Upon reoxidation of the hosts with Ag+, the guests become trapped to provide unprecedented metastable cation-in-cation complexes Cp*2Co+@1a12+ and Cp2Co+@1b12+ that persist for >1 month. Thus, dramatic kinetic effects reveal a way to confine the guests in thermodynamically unfavorable environments. Experimental and DFT studies indicate that PF6- anions kinetically stabilize Cp*2Co+@1a12+ through electrostatic interactions and by influencing conformational changes of the host that open and close its apertures. However, when Cp*2Co+@1a12+ was prepared using ferrocenium (Fc+) instead of Ag+ to reoxidize the host, dissociation was accelerated >200× even though neither Fc+ nor Fc have any observable affinity for 1a12+. This finding shows that metastable host-guest complexes can respond to subtler stimuli than those required to induce guest release from thermodynamically favorable complexes.A prerequisite for environmental and toxicological applications of mercury (Hg) stable isotopes in wildlife and humans is quantifying the isotopic fractionation of biological reactions. Here, we measured stable Hg isotope values of relevant tissues of giant petrels (Macronectes spp.). Isotopic data were interpreted with published HR-XANES spectroscopic data that document a stepwise transformation of methylmercury (MeHg) to Hg-tetraselenolate (Hg(Sec)4) and mercury selenide (HgSe) (Sec = selenocysteine). By mathematical inversion of isotopic and spectroscopic data, identical δ202Hg values for MeHg (2.69 ± 0.04‰), Hg(Sec)4 (-1.37 ± 0.06‰), and HgSe (0.18 ± 0.02‰) were determined in 23 tissues of eight birds from the Kerguelen Islands and Adélie Land (Antarctica). Isotopic differences in δ202Hg between MeHg and Hg(Sec)4 (-4.1 ± 0.1‰) reflect mass-dependent fractionation from a kinetic isotope effect due to the MeHg → Hg(Sec)4 demethylation reaction. Surprisingly, Hg(Sec)4 and HgSe differed isotopically in δ202Hg (+1.6 ± 0.1‰) and mass-independent anomalies (i.e., changes in Δ199Hg of ≤0.3‰), consistent with equilibrium isotope effects of mass-dependent and nuclear volume fractionation from Hg(Sec)4 → HgSe biomineralization. The invariance of species-specific δ202Hg values across tissues and individual birds reflects the kinetic lability of Hg-ligand bonds and tissue-specific redistribution of MeHg and inorganic Hg, likely as Hg(Sec)4. These observations provide fundamental information necessary to improve the interpretation of stable Hg isotope data and provoke a revisitation of processes governing isotopic fractionation in biota and toxicological risk assessment in wildlife.This paper demonstrates the hierarchical design of functional, fibrous polymer monoliths. The monoliths are composed of conjugated microporous polymers that not only are embedded with heteroatoms but also feature fibrous yet compressible structures due to the in situ self-assembly process that occurs during the polymerization process. Therefore, the doped nitrogen atoms can allow the growth of zeolitic imidazolate framework (ZIF) nanocrystals, which causes the homogeneous encapsulation of individual fibers. The resulting hybrid monoliths exhibit enhanced physical properties as well as catalytic activity, allowing the formation of an additional coating layer via a thiol-epoxy reaction. The deliberate inclusion of template molecules during the reaction forms molecularly imprinted sites on the fibers to afford functional monoliths. As a proof of concept, the hierarchically designed materials are able to show effective recognition properties toward diethylstilbestrol, an endocrine disruptor, taking advantage of the binding sites that selectively capture the analyte molecules and the fibrous morphology that increases the accessibility of these binding sites. We envisage that the incorporation of various heteroatoms or nanocrystals will bring about the bespoke design of advanced monoliths with autonomous functions, leading to smart textile systems.Water is essential to protein structure and stability, yet our understanding of how water shapes proteins is far from thorough. Our incomplete knowledge of protein-water interactions is due in part to a long-standing technological inability to assess experimentally how water removal impacts local protein structure. It is now possible to obtain residue-level information on dehydrated protein structures via liquid-observed vapor exchange (LOVE) NMR, a solution NMR technique that quantifies the extent of hydrogen-deuterium exchange between unprotected amide protons of a dehydrated protein and D2O vapor. Here, we apply LOVE NMR, Fourier transform infrared spectroscopy, and solution hydrogen-deuterium exchange to globular proteins GB1, CI2, and two variants thereof to link mutation-induced changes in the dehydrated protein structure to changes in solution structure and stability. We find that a mutation that destabilizes GB1 in solution does not affect its dehydrated structure, whereas a mutation that stabilizes CI2 in solution makes several regions of the protein more susceptible to dehydration-induced unfolding, suggesting that water is primarily responsible for the destabilization of the GB1 variant but plays a stabilizing role in the CI2 variant. Our results indicate that changes in dehydrated protein structure cannot be predicted from changes in solution stability alone and demonstrate the ability of LOVE NMR to uncover the variable role of water in protein stability. Further application of LOVE NMR to other proteins and their variants will improve the ability to predict and modulate protein structure and stability in both the hydrated and dehydrated states for applications in medicine and biotechnology.Cerebrospinal fluid (CSF) leakage from the dura mater during craniotomy is a common complication, which is associated with infection, meningitis, pneumocephalus, and delayed wound healing. In the present study, we developed an absorbable fish gelatin-based anti-inflammatory sealant for dura mater sealing to prevent CSF leakage. Gelatin derived from Alaska pollock (ApGltn) was modified with α-linolenic acid (ALA), an omega-3 fatty acid that exhibits anti-inflammatory properties, and cross-linked with a poly(ethylene glycol)-based cross-linker to develop ALA-ApGltn sealant (ALA-Seal). ALA-Seal demonstrated a higher storage modulus and tangent delta (tan δ) compared with those of the original ApGltn sealant (Org-Seal). The swelling ratio of ALA-Seal was markedly lower than that of DuraSeal, a commercially available dural sealant. Ex vivo burst strength measurements using porcine dura mater indicated that there was no significant difference between DuraSeal and ALA-Seal, despite ALA-Seal having an order of magnitude lower storage modulus. The anti-inflammatory properties of ALA-Seal, evaluated using brain microglial cells, were considerably higher than those of DuraSeal and Org-Seal, with a minimal adverse effect on cell viability. Therefore, compared to DuraSeal, ALA-Seal is a potential dural sealant with a lower swelling ratio, similar burst strength, and higher anti-inflammatory properties, which may prevent CSF leakage.Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose-response curves. link3 Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.Catalysis is an effective way to improve the performance of lithium-sulfur (Li-S) batteries by enhancing the reaction kinetics of polysulfides. However, the bidirectional catalysis for discharging and charging processes in Li-S battery is still challenging. Herein, a (110) facet-dominated VO2 is prepared through the thermal-induced partial decomposition of (NH4)2V4O9 (NVO), forming a (110)VO2@NVO hybrid with the bidirectional catalysis ability. This (110) facet-dominated VO2 shows the ability to break the S-S bond to guide the Li2S deposition in the reduction process and reduce the delithiation barrier of Li2S to promote the oxidation process. The above hybrid is loaded on carbon nanofiber (CNF) to build an interlayer, where the 3D CNF and the conductive NVO ensure the fast electron transfer. The assembled battery with the above interlayer exhibits a high capacity of 1038 mAh g-1 after 300 cycles at 0.1 C (capacity retention 70%). At a high rate of 5 C, a high capacity of 521 mAh g-1 after 1000 cycles is reached.