Circular Polydiketoenamine Elastomers with Exceptional Creep Resistance via Multivalent Cross-Linker Design.

Elastomers are widely used in textiles, foam, and rubber, yet they are rarely recycled due to the difficulty in deconstructing polymer chains to reusable monomers. Introducing reversible bonds in these materials offers prospects for improving their circularity; however, concomitant bond exchange permits creep, which is undesirable. Here, we show how to architect dynamic covalent polydiketoenamine (PDK) elastomers prepared from polyetheramine and triketone monomers, not only for energy-efficient circularity, but also for outstanding creep resistance at high temperature. By appending polytopic cross-linking functionality at the chain ends of flexible polyetheramines, we reduced creep from >200% to less than 1%, relative to monotopic controls, producing mechanically robust and stable elastomers and carbon-reinforced rubbers that are readily depolymerized to pure monomer in high yield. We also found that the multivalent chain end was essential for ensuring complete PDK deconstruction. Mapping reaction coordinates in energy and space across a range of potential conformations reveals the underpinnings of this behavior, which involves preorganization of the transition state for diketoenamine bond acidolysis when a tertiary amine is also nearby.

A global view of aging and Alzheimer's pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains.

Conventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular dynamics in the mammalian brain. Profiling approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles across diverse mouse brains, we identified over 300 cell subtypes, uncovering their molecular characteristics and spatial locations. This comprehensive view elucidates rare cell types expanded or depleted upon aging. We also investigated cell-type-specific responses to genetic alterations linked to Alzheimer's disease, identifying associated rare cell types. Additionally, by profiling 118,240 human brain single-cell transcriptomes, we discerned cell- and region-specific transcriptomic changes tied to Alzheimer's pathogenesis. In conclusion, this research offers a valuable resource for probing cell-type-specific dynamics in both normal and pathological aging.

Assessing the Accuracy of Density Functional Approximations for Predicting Hydrolysis Reaction Kinetics.

Hydrolysis reactions are ubiquitous in biological, environmental, and industrial chemistry. Density functional theory (DFT) is commonly employed to study the kinetics and reaction mechanisms of hydrolysis processes. Here, we present a new data set, Barrier Heights for HydrOlysis - 36 (BH2O-36), to enable the design of density functional approximations (DFAs) and the rational selection of DFAs for applications in aqueous chemistry. BH2O-36 consists of 36 diverse organic and inorganic forward and reverse hydrolysis reactions with reference energy barriers ΔE‡ calculated at the CCSD(T)/CBS level. Using BH2O-36, we evaluate 63 DFAs. In terms of mean absolute error (MAE) and mean relative absolute error (MRAE), ωB97M-V is the best-performing DFA tested, while MN12-L-D3(BJ) is the best-performing pure (nonhybrid) DFA. Broadly, we find that range-separated hybrid DFAs are necessary to approach chemical accuracy (0.043 eV). Although the best-performing DFAs include a dispersion correction to account for long-range interactions, we find that dispersion corrections do not generally improve MAE or MRAE for this data set.

Variable Amine Spacing Determines Depolymerization Rate in Polydiketoenamines.

The design of circular polymers has emerged as a necessity due to the lack of efficient recycling methods for many commodity plastics, particularly those used in durable products. Among the promising circular polymers, polydiketoenamines (PDKs) stand out for their ability to undergo highly selective depolymerization in strong acid, allowing monomers to be recovered from additives and fillers. Varying the triketone monomer in PDK variants is known to strongly affect the depolymerization rate; however, it remains unclear how the chemistry of the cross-linker, far from the reaction center, affects the depolymerization rate. Notably, we found that a proximal amine in the cross-linker dramatically accelerates PDK depolymerization when compared to cross-linkers obviating this functionality. Moreover, the spacing between this amine and the diketoenamine bond offers a previously unexplored opportunity to tune PDK depolymerization rates. In this way, the molecular basis for PDK circularity is revealed and further suggests new targets for the amine monomer design to diversify PDK properties, while ensuring circularity in chemical recycling.

Circularity in mixed-plastic chemical recycling enabled by variable rates of polydiketoenamine hydrolysis.

Footwear, carpet, automotive interiors, and multilayer packaging are examples of products manufactured from several types of polymers whose inextricability poses substantial challenges for recycling at the end of life. Here, we show that chemical circularity in mixed-polymer recycling becomes possible by controlling the rates of depolymerization of polydiketoenamines (PDK) over several orders of magnitude through molecular engineering. Stepwise deconstruction of mixed-PDK composites, laminates, and assemblies is chemospecific, allowing a prescribed subset of monomers, fillers, and additives to be recovered under pristine condition at each stage of the recycling process. We provide a theoretical framework to understand PDK depolymerization via acid-catalyzed hydrolysis and experimentally validate trends predicted for the rate-limiting step. The control achieved by PDK resins in managing chemical and material entropy points to wide-ranging opportunities for pairing circular design with sustainable manufacturing.

Principles and practice for SARS-CoV-2 decontamination of N95 masks with UV-C.

A mainstay of personal protective equipment during the coronavirus disease 2019 pandemic is the N95 filtering facepiece respirator. N95 respirators are commonly used to protect healthcare workers from respiratory pathogens, including the novel coronavirus severe acute respiratory syndrome coronavirus 2, and are increasingly employed by other frontline workers and the general public. Under routine circumstances, these masks are disposable, single-use items, but extended use and reuse practices have been broadly enacted to alleviate critical supply shortages during the coronavirus disease 2019 pandemic. Although extended-time single use presents a low risk of pathogen transfer, repeated donning and doffing of potentially contaminated masks presents increased risk of pathogen transfer. Therefore, efficient and safe decontamination methods for N95 masks are needed to reduce the risk of reuse and mitigate local supply shortages. Here, we review the available literature concerning use of germicidal ultraviolet-C (UV-C) light to decontaminate N95 masks. We propose a practical method for repeated point-of-use decontamination using commercially available UV-C cross-linker boxes from molecular biology laboratories to expose each side of the mask to 800-1200 mJ/cm2 of UV-C. We measure the dose that penetrated to the interior of the respirators and model the potential germicidal action on coronaviruses. Our experimental results, in combination with modeled data, suggest that such a UV-C treatment cycle should induce a >3-log-order reduction in viral bioburden on the surface of the respirators and a 2-log-order reduction throughout the interior. We find that a dose 50-fold greater does not impair filtration or fit of 3M 8210 N95 masks, indicating that decontamination can be performed repeatedly. As such, UV-C germicidal irradiation is a practical strategy for small-scale point-of-use decontamination of N95s.

Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607.

Tau and Aß assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the ß-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.

Phosphorylation of Arp2 is not essential for Arp2/3 complex activity in fission yeast.

LeClaire et al presented evidence that phosphorylation of three sites on the Arp2 subunit activates the Arp2/3 complex to nucleate actin filaments. We mutated the homologous residues of Arp2 (Y198, T233, and T234) in the fission yeast genome to amino acids that preclude or mimic phosphorylation. Arp2/3 complex is essential for the viability of fission yeast, yet strains unable to phosphorylate these sites grew normally. Y198F/T233A/T234A Arp2 was only nonfunctional if GFP-tagged, as observed by LeClaire et al in Drosophila cells. Replacing both T233 and T234 with aspartic acid was lethal, suggesting that phosphorylation might be inhibitory. Nevertheless, blocking phosphorylation at these sites had the same effect as mimicking it: slowing assembly of endocytic actin patches. Mass spectrometry revealed phosphorylation at a fourth conserved Arp2 residue, Y218, but both blocking and mimicking phosphorylation of Y218 only slowed actin patch assembly slightly. Therefore, phosphorylation of Y198, T233, T234, and Y218 is not required for the activity of fission yeast Arp2/3 complex.

Screening conditions for rationally engineered electrodeposition of nanostructures (SCREEN): electrodeposition and applications of polypyrrole nanofibers using microfluidic gradients.

A rapid screening method for optimizing electrochemical deposition conditions of polypyrrole (PPy) nanostructures is reported. An electrochemical cell is integrated within a low-cost microfluidic system, in which electrochemical deposition is carried out across a linear concentration gradient of a reaction parameter. The protocol, refered to as the screening of conditions for rationally engineered electrodeposition of nanostructures (SCREEN), allows rapid screening of conditions for the production of specific morphologies by characterizing the electrodeposited samples produced within a chemical gradient. To demonstrate the utility of the SCREEN method, applications in tunable optical coatings and superhydrophobic surfaces are presented.

Liquid-infused structured surfaces with exceptional anti-biofouling performance.

Bacteria primarily exist in robust, surface-associated communities known as biofilms, ubiquitous in both natural and anthropogenic environments. Mature biofilms resist a wide range of antimicrobial treatments and pose persistent pathogenic threats. Treatment of adherent biofilm is difficult, costly, and, in medical systems such as catheters or implants, frequently impossible. At the same time, strategies for biofilm prevention based on surface chemistry treatments or surface microstructure have been found to only transiently affect initial attachment. Here we report that Slippery Liquid-Infused Porous Surfaces (SLIPS) prevent 99.6% of Pseudomonas aeruginosa biofilm attachment over a 7-d period, as well as Staphylococcus aureus (97.2%) and Escherichia coli (96%), under both static and physiologically realistic flow conditions. In contrast, both polytetrafluoroethylene and a range of nanostructured superhydrophobic surfaces accumulate biofilm within hours. SLIPS show approximately 35 times the reduction of attached biofilm versus best case scenario, state-of-the-art PEGylated surface, and over a far longer timeframe. We screen for and exclude as a factor cytotoxicity of the SLIPS liquid, a fluorinated oil immobilized on a structured substrate. The inability of biofilm to firmly attach to the surface and its effective removal under mild flow conditions (about 1 cm/s) are a result of the unique, nonadhesive, "slippery" character of the smooth liquid interface, which does not degrade over the experimental timeframe. We show that SLIPS-based antibiofilm surfaces are stable in submerged, extreme pH, salinity, and UV environments. They are low-cost, passive, simple to manufacture, and can be formed on arbitrary surfaces. We anticipate that our findings will enable a broad range of antibiofilm solutions in the clinical, industrial, and consumer spaces.

Structural transformation by electrodeposition on patterned substrates (STEPS): a new versatile nanofabrication method.

Arrays of high-aspect-ratio (HAR) nano- and microstructures are of great interest for designing surfaces for applications in optics, bio-nano interfaces, microelectromechanical systems, and microfluidics, but the difficulty of systematically and conveniently varying the geometries of these structures significantly limits their design and optimization for a specific function. This paper demonstrates a low-cost, high-throughput benchtop method that enables a HAR array to be reshaped with nanoscale precision by electrodeposition of conductive polymers. The method-named STEPS (structural transformation by electrodeposition on patterned substrates)-makes it possible to create patterns with proportionally increasing size of original features, to convert isolated HAR features into a closed-cell substrate with a continuous HAR wall, and to transform a simple parent two-dimensional HAR array into new three-dimensional patterned structures with tapered, tilted, anisotropic, or overhanging geometries by controlling the deposition conditions. We demonstrate the fabrication of substrates with continuous or discrete gradients of nanostructure features, as well as libraries of various patterns, starting from a single master structure. By providing exemplary applications in plasmonics, bacterial patterning, and formation of mechanically reinforced structures, we show that STEPS enables a wide range of studies of the effect of substrate topography on surface properties leading to optimization of the structures for a specific application. This research identifies solution-based deposition of conductive polymers as a new tool in nanofabrication and allows access to 3D architectures that were previously difficult to fabricate.

Bacterial biofilm shows persistent resistance to liquid wetting and gas penetration.

Most of the world's bacteria exist in robust, sessile communities known as biofilms, ubiquitously adherent to environmental surfaces from ocean floors to human teeth and notoriously resistant to antimicrobial agents. We report the surprising observation that Bacillus subtilis biofilm colonies and pellicles are extremely nonwetting, greatly surpassing the repellency of Teflon toward water and lower surface tension liquids. The biofilm surface remains nonwetting against up to 80% ethanol as well as other organic solvents and commercial biocides across a large and clinically important concentration range. We show that this property limits the penetration of antimicrobial liquids into the biofilm, severely compromising their efficacy. To highlight the mechanisms of this phenomenon, we performed experiments with mutant biofilms lacking ECM components and with functionalized polymeric replicas of biofilm microstructure. We show that the nonwetting properties are a synergistic result of ECM composition, multiscale roughness, reentrant topography, and possibly yet other factors related to the dynamic nature of the biofilm surface. Finally, we report the impenetrability of the biofilm surface by gases, implying defense capability against vapor-phase antimicrobials as well. These remarkable properties of B. subtilis biofilm, which may have evolved as a protection mechanism against native environmental threats, provide a new direction in both antimicrobial research and bioinspired liquid-repellent surface paradigms.

Organic-inorganic interfaces and spiral growth in nacre.

Nacre, the crown jewel of natural materials, has been extensively studied owing to its remarkable physical properties for over 160 years. Yet, the precise structural features governing its extraordinary strength and its growth mechanism remain elusive. In this paper, we present a series of observations pertaining to the red abalone (Haliotis rufescens) shell's organic-inorganic interface, organic interlayer morphology and properties, large-area crystal domain orientations and nacre growth. In particular, we describe unique lateral nano-growths and paired screw dislocations in the aragonite layers, and demonstrate that the organic material sandwiched between aragonite platelets consists of multiple organic layers of varying nano-mechanical resilience. Based on these novel observations and analysis, we propose a spiral growth model that accounts for both [001] vertical propagation via helices that surround numerous screw dislocation cores and simultaneous 010 lateral growth of aragonite sheet structure. These new findings may aid in creating novel organic-inorganic micro/nano composites through synthetic or biomineralization pathways.