Molecular Bridging Research Articles

Polyimide Hybrid Nanocomposites with Controlled Polymer Filling and Polymer-Matrix Interaction.

Polyimide hybrid nanocomposites with the polyimide confined at molecular length scales exhibit enhanced fracture resistance with excellent thermal-oxidative stability at low density. Previously, polyimide nanocomposites were fabricated by infiltration of a polyimide precursor into a nanoporous matrix followed by sequential thermally induced imidization and cross-linking of the polyimide under nanometer-scale confinement. However, byproducts formed during imidization became volatile at the cross-linking temperature, limiting the polymer fill level and degrading the nanocomposite fracture resistance. This is solved in the present work with an easier approach where the nanoporous matrix is filled with shorter preimidized polyimide chains that are cross-linked while in the pores to eliminate the need for confined imidization reactions, which produces better results compared to the previous study. In addition, we selected a preimidized polyimide that has a higher chain mobility and a stronger interaction with the matrix pore surface. Consequently, the toughness achieved with un-cross-linked preimidized polyimide chains in this work is equivalent to that achieved with the cross-linking of the previously used polyimide chains and is doubled when preimidized polyimide chains are cross-linked. The increased chain mobility enables more efficient polymer filling and higher polymer fill levels. The higher polymer-pore surface interaction increases the energy dissipation during polyimide molecular bridging, increasing the nanocomposite fracture resistance. The combination of the higher polymer fill and the stronger polymer-surface interaction is shown to provide significant improvements to the nanocomposite fracture resistance and is validated with a molecular bridging model.

Molecular Bridging Enables Isolated Iron Atoms on Stereoassembled Carbon Framework To Boost Oxygen Reduction for Zinc-Air Batteries.

Realizing the synergy between active site regulation and rational structural engineering is essential in the electrocatalysis community but still challenging. Here, a matrix-confined co-pyrolysis strategy based on molecular bridging is demonstrated to realize highly dispersed Fe atoms on stereoassembled carbon framework. Both polyacrylonitrile matrix and organic linker from metal-organic frameworks (MOFs) provide sufficient N-anchoring sites for the generation of Fe-N4 moieties. A high Fe loading of 2.9 wt.% is readily achieved based on the scalable approach without post-treatment. Owing to the presence of highly exposed Fe-N-C sites and well-tuned pore structures, isolated Fe atoms on porous carbon nanofiber framework (Fe-SA/NCF) exhibits decent oxygen reduction activity and stability in alkaline conditions via a near four-electron path, demonstrating superior performance as air cathode for zinc-air batteries (ZABs) to commercial Pt/C catalyst.

Is the “Bricks-and-Mortar” Mesophase Bicontinuous? Dynamic Simulations of Miktoarm Block Copolymer/Homopolymer Blends

A new mesophase in binary blends of A–b–(BA′)3 miktoarm star block copolymers and A homopolymers has recently been discovered experimentally and explored with field-theoretic simulations. This mesophase has been reported to consist of aperiodic discrete domains of A embedded in a continuous matrix of B up to very high concentrations of A. Because of the material’s potential as a thermoplastic elastomer, a deeper understanding of its structural and dynamic-mechanical properties, including its domain connectivity, linear rheological behavior, response to shear, and response to uniaxial tension, is warranted. These properties are explored here using dissipative particle dynamics in three dimensions, for the first time. These simulations establish that the so-called “bricks-and-mortar” phase, while appearing discrete in two dimensions, is bicontinuous. The simulations focusing on dynamics establish that the role of molecular bridging dominates the mechanical behavior and outweighs the influence of microphase segregation (contributions from the interfacial tension alone) even at the highest homopolymer concentrations we study. Additionally, it appears that the bricks-and-mortar phase is sensitive to the application of sufficiently high shear, leading to nonisotropic mechanical responses, which has ramifications for the processability of such materials. We find that upon application of shear the phase becomes closer in structure to its speculated discrete nature. Molecular simulations on our longest accessible timescales show that the material is unable to relax back to its original structure, suggesting that the morphology observed depends heavily on the material process pathway.

Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration.

For patients with osteoporosis, the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation, migration, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). To improve bone-implant integration in osteoporotic condition, here we reported a one-step biomimetic surface strategy to introduce BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. In our design, the bioadhesive molecular peptide mimic inspired by mussel foot proteins (Mfps) was used as molecular bridging for surface functionalization. Specifically, a BMSC-targeting peptide sequence (E7) and an osteogenic growth peptide (Y5) were grafted onto the titanium implant surfaces through a mussel adhesion mechanism. We found that a rational E7/Y5 feeding ratio could lead to an optimal dual functionalization capable of not only significantly improving the biocompatibility of the implant but also enabling it to recruit endogenous BMSCs for colonization, proliferation, and osteogenic differentiation. Mechanistically, the E7-assisted in situ recruitment of endogenous BMSCs as well as the enhanced interfacial osteogenesis and osteointegration was associated with activation of the C-X-C chemokine receptor type 4 (CXCR4) receptor on the cell surface and promotion of stromal cell-derived factor (SDF-1α) autocrine secretion. We anticipated that rational dual-functional surfaces through bioadhesive molecular mimics will provide a simple, effective, nonimmunogenic, and safe means to improve the clinical outcomes of intraosseous implants, especially under osteoporotic conditions.

Isolation of thermostable cellulose II nanocrystals and their molecular bridging for electroresponsive and pH-sensitive bio-nanocomposite

Sustainable, economical, and green extraction of cellulose Ⅱ nanocrystals from lignocellulose under mild conditions is still challenging since the highly recalcitrant nature of lignocellulose. Herein, a sustainable system using ammonium persulfate (APS)-catalyzed deep eutectic solvent (ADES) was developed to produce functional cellulose Ⅱ nanocrystals (CNCs) with a high yield of 82.3 %. The obtained CNCs had excellent thermal stability (>350 ℃), high crystallinity of 76.6 % with surface carboxyl groups, and superior dispersion stability. CNCs played a role of both molecular bridging and nano-sized effect in gelatin matrix, which combined with gelatin tightly through multiple hydrogen bonds to prepare bio-nanocomposite films with outstanding electric-responsiveness and pH-sensitivity. It was proved that CNCs had remarkable reinforcing potential and effective stress transfer capacity, contributing to a 187 % enhancement in tensile strength and an approximately 110 % increase in Young’s modulus of the formed CNCs/gelatin nanocomposite films when 0.5 wt % CNCs was loaded. Therefore, the study may open the door for developing a green and sustainable avenue to produce functional CNCs, and is of great significance for the building of CNCs-based functional nanocomposites.

Investigation of Molecular Bridging Using Atom Migration in Nanogap Electrodes

Investigation of Molecular Bridging Using Atom Migration in Nanogap Electrodes

Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial

ObjectiveTo determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when warfarin is temporarily interrupted for a planned...

Atomically Precise Insights into Metal–Metal Bonds Using Comparable Endo-Units of Sc 2 and Sc 2 C 2

The precise identification of metal–metal bonds is critical to fully understanding the nature of metal–metal bonding but remains a fundamental challenge. Herein, we show the essence of Sc–Sc bonds ...

Molecular dynamics simulations of separator-cathode interfacial thermal transport in a Li-ion cell

While Li-ion cells show outstanding electrochemical performance, their poor thermal transport characteristics result in reduced performance as well as significant safety concerns. The heterogeneous interface between cathode and separator plays a vital role in the process of thermal conduction in a Li-ion cell. Recent experiments have shown that the cathode-separator interfacial thermal resistance contributes significantly to total thermal resistance within the cell. In this paper, thermal conductance across the cathode-separator interface is calculated using molecular dynamics (MD) simulations with IFF-CVFF force field. Thermal transport in a pristine heterogeneous interface as well as when bridged with 3-Aminopropyl triethoxysilane (APTES), n-Butyl trimethoxysilane (nBTMS) and 3-Mercaptopropyl trimethoxysilane (MPTMS) molecules is computed. It is shown that molecular bridging at the interface results in up to 250% improvement in interfacial thermal conductance for the APTES case, which is consistent with recent experimental data. These results quantify the key role of the cathode-separator interface in thermal transport within the Li-ion cell, as well as the potential improvement in interfacial thermal transport by molecular bridging. The techniques and results discussed here may help downselect molecular species for interfacial thermal transport enhancement in Li-ion cells.

Bioinspired Molecular Bridging in a Hybrid Perovskite Leads to Enhanced Stability and Tunable Properties

AbstractHybrid perovskites demonstrate high potential in optoelectronic applications. Their main drawback is their low stability under humid conditions. In this paper, one of nature's strategies is implemented—the incorporation of amino acids into the crystal lattice—in order to improve the stability of methylammonium lead bromide (MAPbBr3) in water, and to tune its structure, as well as its optical and thermal properties. The amino acid lysine, which possesses two NH3+ groups, is incorporated into the hybrid unit cell, by substituting two methylammonium ions and serves as a “molecular bridge”. This incorporation induces a decrease in the lattice parameter of the host, accompanied with an increase in its bandgap and noticeable changes in its morphology. Furthermore, a substantial decrease in the thermal expansion coefficient of MAPbBr3 and a shift of its cubic‐to‐tetragonal phase transformation temperature are observed. Two different modes of incorporation are identified, which depend on the conditions of crystallization. These modes dictate the level of lysine incorporation and the magnitude of MAPbBr3 bandgap changes. Notably, lysine incorporation strongly increases the perovskite stability in water. This study demonstrates a unique and promising approach to tune the properties and improve the stability of hybrid perovskites via this novel bioinspired route.

Influence of environmental and biological macromolecules on aggregation kinetics of nanoplastics in aquatic systems

Nanoplastics derived from degradation of micro- or macroplastics are emerging contaminants in aquatic environments, where their fate and transport as well as toxicity are affected by aggregation. This study employed time-resolved dynamic light scattering to investigate the aggregation kinetics of polystyrene nanoplastics (PSNPs) in the presence of four macromolecules (sodium alginate (SA), bovine serum albumin (BSA), extracellular polymeric substance (EPS), and Suwannee River humic acid (HA)) in solutions containing monovalent (NaCl) and divalent (CaCl2) salts at different pH. Our results showed that the macromolecules enhanced PSNP stability in NaCl solutions but destabilized PSNPs in CaCl2 solutions at pH 6. In NaCl solutions, macromolecules inhibited PSNP aggregation due to steric hindrance originated from macromolecular layer adsorbed on PSNPs. The strongest stabilization effect was observed for BSA having the greatest hydrodynamic adsorption layer thickness of 21.9 nm, followed by HA, EPS, and SA. In CaCl2 solutions, SA significantly destabilized PSNPs via alginate bridging with Ca2+, which enhanced with concentrations of SA and CaCl2. The destabilization effects of other three macromolecules in CaCl2 solutions were governed by the interplay among molecular bridging, charge screening, and steric hindrance. An increased pH in NaCl or CaCl2 solutions containing macromolecules all stabilized PSNPs due to elevated electrostatic repulsion, except that SA destabilized PSNPs in CaCl2 solutions via enhanced molecular bridging. The stabilization effect of macromolecules may also compete with the destabilization effect under seawater condition. This study suggested that PSNP aggregation in aquatic environments could be strongly affected by macromolecules and solution chemistry.

Single-Molecular Bridging in Static Metal Nanogap Electrodes Using Migrations of Metal Atoms

The realization of molecular devices via metal–molecule–metal junctions necessitates the fabrication of a steady molecular bridging structure, where the number of bridging structures should be fixe...

Systematic study of low energy geometries of copper nano-junctions exposed to water and to species that can result from dissociation of water

A detailed computational analysis has been performed, considering copper atomic contacts that are exposed directly to water molecules, hydroxyl groups, and monatomic as well as molecular hydrogen and oxygen species. The optimized physical bonding structure, electrical conductance and inelastic tunneling spectra (IETS) have been determined theoretically for moderately large structures by performing appropriate ab initio and semi-empirical calculations. By considering the aforementioned properties, it has been possible to determine that some of the molecular bridging structures may be regarded as being highly-probable outcomes, resulting from the exposure of copper electrodes to the atomic/molecular contaminants. We specifically identify the conductance properties of a variety of configurations including examples with very high and very low conductance values. This is done in order to identify junction geometries that may be realized experimentally and their conductance and IETS signatures. By reporting geometries with very high and very low conductance values here, we intend to provide a wider perspective view than previous studies of copper-molecular junctions that have focused on high conductance structures. In addition, we explore the properties of metal junctions with multiple molecules, a class of systems for which little theoretical work has been available in the molecular electronics literature. We find that water molecules surrounding the junction can influence the bonding geometry of the molecules within the junction and consequently can affect strongly the calculated conductances of such junctions.

Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection.

“Functional cure” is being pursued as the ultimate endpoint of antiviral treatment in chronic hepatitis B (CHB), which is characterized by loss of HBsAg whether or not anti-HBs antibodies are present. “Functional cure” can be achieved in <10% of CHB patients with currently available therapeutic agents. The dysfunction of specific immune responses to hepatitis B virus (HBV) is considered the major cause of persistent HBV infection. Thus, modulating the host immune system to strengthen specific cellular immune reactions might help eliminate HBV. Strategies are needed to restore/enhance innate immunity and induce HBV-specific adaptive immune responses in a coordinated way. Immune and resident cells express pattern recognition receptors like TLRs and RIG I/MDA5, which play important roles in the induction of innate immunity through sensing of pathogen-associated molecular patterns (PAMPs) and bridging to adaptive immunity for pathogen-specific immune control. TLR/RIG I agonists activate innate immune responses and suppress HBV replication in vitro and in vivo, and are being investigated in clinical trials. On the other hand, HBV-specific immune responses could be induced by therapeutic vaccines, including protein (HBsAg/preS and HBcAg), DNA, and viral vector-based vaccines. More than 50 clinical trials have been performed to assess therapeutic vaccines in CHB treatment, some of which display potential effects. Most recently, using genetic editing technology to generate CAR-T or TCR-T, HBV-specific T cells have been produced to efficiently clear HBV. This review summarizes the progress in basic and clinical research investigating immunomodulatory strategies for curing chronic HBV infection, and critically discusses the rather disappointing results of current clinical trials and future strategies.

Enabling Molecular Gapping and Bridging on a Biosensing Surface via Electrochemical Cross-Linking and Cleavage.

Protein detection in complicated biological samples requires robust design and a rigorous rinsing process. Many recently developed artificial targeting probes, however, often do not possess antibody-like binding strength that enables them to endure harsh biosensing conditions, and the classic 2-to-1 sandwich binding pattern is unavailable for many targets, often necessitating a complicated indirect signal conversion mechanism. Here, an attempt is made to provide innovative "covalent" solutions to such problems by employing peptide reactivity to form a covalent and robust biosensing structure upon target binding. Both the cross-coupling and cleavage of peptide chains are employed to achieve the classic 2-to-1 binding when only one targeting probe is available. Specifically, a targeting probe against the protein and a signaling probe are coimmobilized onto the sensing interface. The ratio between the two probes and their surface density is modulated so that direct cross-linking between the two immobilized probes is suppressed by the average distance between two such probes. Upon protein binding, the protein molecule may bridge that gap by itself. The signaling probe can carry any motif of signal amplification. And here a Cu-ion-complexed motif, which can exhibit peroxidase-like activity upon electrochemical agitation, is employed multipurposely as the catalyst for cross-linking, cleavage, and signal amplification. Three nonhomologous target proteins can be sensitively quantified in serum-spiked samples and clinical sample detection of one of them is also successful; these results suggest the potential of the proposed method in future clinical applications.

Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells

The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells have reduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically, Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respiration rates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK and mTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together, our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signaling with downstream metabolic burst and NK cell expansion.

Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex.

N6-methyladenosine (m6A) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying m6A-mediated gene regulation is poorly understood. Here, we show that m6A-containing RNAs are subject to endoribonucleolytic cleavage via YTHDF2 (m6A reader protein), HRSP12 (adaptor protein), and RNase P/MRP (endoribonucleases). We demonstrate that HRSP12 functions as an adaptor to bridge YTHDF2 and RNase P/MRP, eliciting rapid degradation of YTHDF2-bound RNAs. Transcriptome-wide analyses show that m6A RNAs that are preferentially targeted for endoribonucleolytic cleavage have an HRSP12-binding site and a RNase P/MRP-directed cleavage site upstream and downstream of the YTHDF2-binding site, respectively. We also find that a subset of m6A-containing circular RNAs associates with YTHDF2 in an HRSP12-dependent manner and is selectively downregulated by RNase P/MRP. Thus, our data expand the known functions of RNase P/MRP to endoribonucleolytic cleavage of m6A RNAs.

Double Blind Randomized Control Trial of Postoperative Low Molecular Weight Heparin Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2)

▪BackgroundIt remains uncertain if patients with atrial fibrillation or mechanical heart valves requiring interruption of warfarin for procedures benefit from post-procedure anticoagulant bridging therapy.MethodsIn order to determine the efficacy and safety of postoperative LMWH bridging, we conducted a multicenter randomized double-blind controlled trial of patients with atrial fibrillation or a mechanical heart valve who require interruption of warfarin for a planned procedure. We excluded patients with active bleeding within 30 days, platelet count <100 x10⁹/L, spinal, cardiac or neurosurgery, life expectancy <3months, creatinine clearance <30ml/min, multiple mechanical valves or a Starr-Edwards valve, mechanical valve with history of stroke or TIA, or a history of heparin induced thrombocytopenia. The last dose of warfarin was given 6 days prior to the procedure. All patients received pre-procedure bridging therapy with dalteparin 200 IU per kilogram (max 18,000 IU) subcutaneously in the morning day-3 and day-2 then dalteparin 100 IU per kilogram (max 18,000 IU) subcutaneously 24 hours pre-procedure. Warfarin was resumed in the evening of the procedure at twice the usual dose for the first two days and then titrated according to INR. After the procedure (same day or next day), when hemostasis had been achieved, patients were randomized to receive dalteparin or placebo for at least 4 days and until the INR was greater than 1.9. Randomization was stratified by presence of a mechanical valve, by the post-procedure risk for major bleeding, and by centre. For patients at high risk for post-procedure major bleeding, dalteparin or placebo was administered at a fixed daily dose of 5000 IU. For patients at low risk for post-procedure major bleeding, dalteparin or placebo was administered at a daily dose of 200 IU per kilogram (max 18,000 IU). The primary analysis was a comparison of the proportion of patients who had major thromboembolism (stroke, proximal DVT, PE, MI, peripheral embolism) over 90 days by Chi-squared test according to the intention to treat principle. Secondary outcomes were major bleeding, all cause mortality and a composite outcome of major thromboembolism and major bleeding.ResultsStarting in October 2006 we randomized a total of 1471 patients of whom 1167 had atrial fibrillation (without mechanical heart valves) and 304 had mechanical valves (99 also had atrial fibrillation). Last follow up was completed in May 2016. Baseline characteristics were similar between the LMWH and the placebo groups (see Table 1). Due to a randomization program system error at two centres more atrial fibrillation patients were randomized to dalteparin rather than to placebo. Major thromboembolism occurred in 6/820 (0.71%) dalteparin patients and 7/650 (1.11%) placebo patients. Major post-procedure bleeding occurred in 12 (1.46%) dalteparin patients and 16 (2.46%) placebo patients. Findings were similar in patients with atrial fibrillation alone and in patients with mechanical heart valves (with or without atrial fibrillation) (Table 2).ConclusionsIn patients with atrial fibrillation and/or mechanical heart valves who had warfarin interrupted for a procedure there was no benefit from post-procedure LMWH bridging. [Display omitted] DisclosuresKovacs:Bayer: Research Funding; Daiichi Sankyo Pharma Development: Research Funding. Wells:Janssen: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Bayer: Honoraria. Schulman:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

Using Unentangled Oligomers To Toughen Materials.

Entanglements between polymer chains are responsible for the strength and toughness of polymeric materials. When the chains are too short to form entanglements, the polymer becomes weak and brittle. Here we show that molecular bridging of oligomers in molecular-scale confinement can dramatically toughen materials even when intermolecular entanglements are completely absent. We describe the fabrication of nanocomposite materials that confine oligomer chains to molecular-scale dimensions and demonstrate that partially confined unentangled oligomers can toughen materials far beyond rule-of-mixtures estimates. We also characterize how partially confined oligomers affect the kinetics of nanocomposite cracking in moist environments and show that the presence of a backfilled oligomeric phase within a nanoporous organosilicatematrix leads to atomistic crack path meandering in which the failure path is preferentially located within the matrix phase.

Relaxation Dynamics of Electronically Coupled Au20(SC8H9)15-n-glyme-Au20(SC8H9)15 Monolayer-Protected Cluster Dimers

The electronic relaxation dynamics of photoexcited Au20(SC8H9)15-n-glyme and Au20(SC8H9)15-n-glyme-Au20(SC8H9)15 (n- = di-, tri-, and tetra-) dimers, where glyme refers to n-ethylene glycol dimethyl ether bridging molecules, were studied using pump–probe femtosecond time-resolved transient absorption spectroscopy (fsTAS). The utilization of n-glyme molecular bridging linkers provided a method to prepare Au20(SC8H9)15-n-glyme-Au20(SC8H9)15 dimers with control over intercluster spatial separation. A dimer-specific electronic absorption resonance was observed at 2.6 eV. Analysis of fsTAS differential spectra for dimer species revealed a pump–probe waiting time-dependent blue shift of the low energy excited-state absorption (ESA) feature, suggesting electronic relaxation into a dimer-specific excited-state. Single probe-energy differential signal amplitude analysis of the ESA feature yielded a distance-dependent growth component for the electronic relaxation dynamics with time constants of 130 ± 20, 60 ± 8, a...