Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models.

Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aß oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal. These apoptotic-like spines are targeted by microglia for engulfment via TREM2 leading to amelioration of Aß oligomer-induced synaptic hyperactivity. We also show the in vivo relevance of ePtdSer-TREM2 signaling in microglia-synapse engulfment in the hAPP NL-F knock-in mouse model of AD. Higher levels of apoptotic-like synapses in mice as well as humans that carry TREM2 loss-of-function variants were also observed. Our work supports that microglia remove hyperactive ePtdSer+ synapses in Aß-relevant context and suggest a potential beneficial role for microglia in the earliest stages of AD.

Artificial Intelligence Applied to Battery Research: Hype or Reality?

This is a critical review of artificial intelligence/machine learning (AI/ML) methods applied to battery research. It aims at providing a comprehensive, authoritative, and critical, yet easily understandable, review of general interest to the battery community. It addresses the concepts, approaches, tools, outcomes, and challenges of using AI/ML as an accelerator for the design and optimization of the next generation of batteries─a current hot topic. It intends to create both accessibility of these tools to the chemistry and electrochemical energy sciences communities and completeness in terms of the different battery R&D aspects covered.

SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation.

Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters a dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells in a perniciously reactive state that often enhances neuronal damage. The molecular components that mediate this critical communication are not fully explored. Here, we show that secreted frizzled-related protein 1 (SFRP1), a multifunctional regulator of cell-to-cell communication, is part of the cellular crosstalk underlying neuroinflammation. In mouse models of acute and chronic neuroinflammation, SFRP1, largely astrocyte-derived, promotes and sustains microglial activation, and thus a chronic inflammatory state. SFRP1 promotes the upregulation of components of the hypoxia-induced factor-dependent inflammatory pathway and, to a lower extent, of those downstream of the nuclear factor-kappa B. We thus propose that SFRP1 acts as an astrocyte-to-microglia amplifier of neuroinflammation, representing a potential valuable therapeutic target for counteracting the harmful effect of chronic inflammation in several neurodegenerative diseases.

Synergistic theoretical and experimental study on the ion dynamics of bis(trifluoromethanesulfonyl)imide-based alkali metal salts for solid polymer electrolytes.

Model validation of a well-known class of solid polymer electrolyte (SPE) is utilized to predict the ionic structure and ion dynamics of alternative alkali metal ions, leading to advancements in Na-, K-, and Cs-based SPEs for solid-state alkali metal batteries. A comprehensive study based on molecular dynamics (MD) is conducted to simulate ion coordination and the ion transport properties of poly(ethylene oxide) (PEO) with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt across various LiTFSI concentrations. Through validation of the MD simulation results with experimental techniques, we gain a deeper understanding of the ionic structure and dynamics in the PEO/LiTFSI system. This computational approach is then extended to predict ion coordination and transport properties of alternative alkali metal ions. The ionic structure in PEO/LiTFSI is significantly influenced by the LiTFSI concentration, resulting in different lithium-ion transport mechanisms for highly concentrated or diluted systems. Substituting lithium with sodium, potassium, and cesium reveals a weaker cation-PEO coordination for the larger cesium-ion. However, sodium-ion based SPEs exhibit the highest cation transport number, indicating the crucial interplay between salt dissociation and cation-PEO coordination for achieving optimal performance in alkali metal SPEs.

Anion π-π Stacking for Improved Lithium Transport in Polymer Electrolytes.

Polymer electrolytes (PEs) with excellent flexibility, processability, and good contact with lithium metal (Li°) anodes have attracted substantial attention in both academic and industrial settings. However, conventional poly(ethylene oxide) (PEO)-based PEs suffer from a low lithium-ion transference number (TLi+), leading to a notorious concentration gradient and internal cell polarization. Here, we report two kinds of highly lithium-ion conductive and solvent-free PEs using the benzene-based lithium salts, lithium (benzenesulfonyl)(trifluoromethanesulfonyl)imide (LiBTFSI) and lithium (2,4,6-triisopropylbenzenesulfonyl)(trifluoromethanesulfonyl)imide (LiTPBTFSI), which show significantly improved TLi+ and selective lithium-ion conductivity. Using molecular dynamics simulations, we pinpoint the strong π-π stacking interaction between pairs of benzene-based anions as the cause of this improvement. In addition, we show that Li°âˆ¥Li° and Li°âˆ¥LiFePO4 cells with the LiBTFSI/PEO electrolytes present enhanced cycling performance. By considering π-π stacking interactions as a new molecular-level design route of salts for electrolyte, this work provides an efficient and facile novel strategy for attaining highly selective lithium-ion conductive PEs.

Modeling magnesium surfaces and their dissolution in an aqueous environment using an implicit solvent model.

Magnesium has attracted growing interest for its use in various applications, primarily due to its abundance, lightweight properties, and relatively low cost. However, one major drawback to its widespread use remains to be its reactivity in aqueous environments, which is poorly understood at the atomistic level. Ab initio density functional theory methods are particularly well suited to bridge this knowledge gap, but the explicit simulation of electrified water/metal interfaces is often too costly from a computational viewpoint. Here, we investigate water/Mg interfaces using the computationally efficient implicit solvent model VASPsol. We show that the Mg (0001), (101̄0), and (101̄1) surfaces each form different electrochemical double layers due to the anisotropic smoothing of the electron density at their surfaces, following Smoluchowski rules. We highlight the dependence that the position of the diffuse cavity surrounding the interface has on the potential of zero charge and the electron double layer capacitance, and how these parameters are also affected by the addition of explicit water and adsorbed OH molecules. Finally, we calculate the equilibrium potential of Mg2+/Mg0 in an aqueous environment to be -2.46 V vs a standard hydrogen electrode, in excellent agreement with the experiment.

Towards tuning the modality of hierarchical macro-nanoporous metals by controlling the dealloying kinetics of close-to-eutectic alloys.

Largely inspired by nature, hierarchical porous materials are attractive for a wide range of applications as they provide a unique combination of transport and interfacial properties. Hierarchical macro-nanoporous metals (HMNPM) are of particular interest due to their high thermal and electrical conductivities, high volumetric macroporosity as well as their strong capillary forces, and large surface area due to their nanopores. However, tuning the porosity of HMNPMs remains challenging and often requires complex multi-step synthesis methods. Here we demonstrate that controlling the dealloying kinetics of close-to-eutectic alloys allows the selective tuning of the porosity of a hierarchical metal from tens of nanometers to hundreds of micrometers. This was demonstrated by dealloying the Cu-Mg-Zn alloy of close-to-eutectic composition to develop trimodal hierarchical macro-nanoporous copper with an impressive porosity of 94 vol% in the form of macroscopic self-supporting bulk samples. A combination of dealloying experiments and density functional theory calculations indicate that while selective corrosion of chemical phases in the Cu-Mg-Zn alloy is triggered according to their Volta potential, the kinetics can be altered by confinement and non-homogeneity effects. The obtained insights into the kinetics of close-to-eutectic alloy dealloying can be used to develop other hierarchical porous metals with tunable porosity and controlled shape.

Suppressed Mobility of Negative Charges in Polymer Electrolytes with an Ether-Functionalized Anion.

Suppressing the mobility of anionic species in polymer electrolytes (PEs) is essential for mitigating the concentration gradient and internal cell polarization, and thereby improving the stability and cycle life of rechargeable alkali metal batteries. Now, an ether-functionalized anion (EFA) is used as a counter-charge in a lithium salt. As the salt component in PEs, it achieves low anionic diffusivity but sufficient Li-ion conductivity. The ethylene oxide unit in EFA endows nanosized self-agglomeration of anions and trapping interactions between the anions and its structurally homologous matrix, poly(ethylene oxide), thus suppressing the mobility of negative charges. In contrast to previous strategies of using anion traps or tethering anions to a polymer/inorganic backbone, this work offers a facile and elegant methodology on accessing selective and efficient Li-ion transport in PEs and related electrolyte materials (for example, composites and hybrid electrolytes).

Enhanced Lithium-Ion Conductivity of Polymer Electrolytes by Selective Introduction of Hydrogen into the Anion.

The anion chemistry of lithium salts plays a pivotal role in dictating the physicochemical and electrochemical performance of solid polymer electrolytes (SPEs), thus affecting the cyclability of all-solid-state lithium metal batteries (ASSLMBs). The bis(trifluoromethanesulfonyl)imide anion (TFSI- ) has long been studied as the most promising candidate for SPEs; however, the Li-ion conductivities of the TFSI-based SPEs still remain low (Li-ion transference number: ca. 0.2). In this work, we report new hydrogen-containing anions, conceived based on theoretical considerations, as an electrolyte salt for SPEs. SPEs comprising hydrogen-containing anions achieve higher Li-ion conductivities than TFSI-based ones, and those anions are electrochemically stable for various kinds of ASSLMBs (Li-LiFePO4 , Li-S, and Li-O2 batteries). This opens up a new avenue for designing safe and high-performance ASSLMBs in the future.

Ultrahigh Performance All Solid-State Lithium Sulfur Batteries: Salt Anion's Chemistry-Induced Anomalous Synergistic Effect.

With a remarkably higher theoretical energy density compared to lithium-ion batteries (LIBs) and abundance of elemental sulfur, lithium sulfur (Li-S) batteries have emerged as one of the most promising alternatives among all the post LIB technologies. In particular, the coupling of solid polymer electrolytes (SPEs) with the cell chemistry of Li-S batteries enables a safe and high-capacity electrochemical energy storage system, due to the better processability and less flammability of SPEs compared to liquid electrolytes. However, the practical deployment of all solid-state Li-S batteries (ASSLSBs) containing SPEs is largely hindered by the low accessibility of active materials and side reactions of soluble polysulfide species, resulting in a poor specific capacity and cyclability. In the present work, an ultrahigh performance of ASSLSBs is obtained via an anomalous synergistic effect between (fluorosulfonyl)(trifluoromethanesulfonyl)imide anions inherited from the design of lithium salts in SPEs and the polysulfide species formed during the cycling. The corresponding Li-S cells deliver high specific/areal capacity (1394 mAh gsulfur-1, 1.2 mAh cm-2), good Coulombic efficiency, and superior rate capability (∼800 mAh gsulfur-1 after 60 cycles). These results imply the importance of the molecular structure of lithium salts in ASSLSBs and pave a way for future development of safe and cost-effective Li-S batteries.

Magnetism of NaFePO4 and related polyanionic compounds.

Magnetic properties of maricite (m) and triphlyte (t) polymorphs of NaFePO4 are investigated by combining ab initio density functional theory with a model Hamiltonian approach, where a realistic Hubbard-type model for magnetic Fe 3d states in NaFePO4 is constructed entirely from first-principles calculations. For these purposes, we perform a comparative study based on the pseudopotential and linear muffin-tin orbital methods while tackling the problem of parasitic non-sphericity of the exchange-correlation potential. Upon calculating the model parameters, magnetic properties are studied by applying the mean-field Hartree-Fock approximation and the theory of superexchange interactions to extract the corresponding interatomic exchange parameters. Despite some differences, the two methods provide a consistent description of the magnetic properties of NaFePO4. On the one hand, our calculations reproduce the correct magnetic ordering for t-NaFePO4 allowing for magnetoelectric effect, and the theoretical values of Néel and Curie-Weiss temperatures are in fair agreement with reported experimental data. Furthermore, we investigate the effect of chemical pressure on magnetic properties by substituting Na with Li and, in turn, we explain how a noncollinear magnetic alignment induced by an external magnetic field leads to magnetoelectric effect in NaFePO4 and other transition-metal phosphates. However, the origin of a magnetic superstructure with q = (1/2, 0, 1/2) observed experimentally in m-NaFePO4 remains puzzling. Instead, we predict that competing exchange interactions can lead to the formation of magnetic superstructures along the shortest orthorhombic c axis of m-NaFePO4, similar to multiferroic manganites.

Chirality at two-dimensional surfaces: A perspective from small molecule alcohol assembly on Au(111).

The delicate balance between hydrogen bonding and van der Waals interactions determines the stability, structure, and chirality of many molecular and supramolecular aggregates weakly adsorbed on solid surfaces. Yet the inherent complexity of these systems makes their experimental study at the molecular level very challenging. In this quest, small alcohols adsorbed on metal surfaces have become a useful model system to gain fundamental insight into the interplay of such molecule-surface and molecule-molecule interactions. Here, through a combination of scanning tunneling microscopy and density functional theory, we compare and contrast the adsorption and self-assembly of a range of small alcohols from methanol to butanol on Au(111). We find that longer chained alcohols prefer to form zigzag chains held together by extended hydrogen bonded networks between adjacent molecules. When alcohols bind to a metal surface datively via one of the two lone electron pairs of the oxygen atom, they become chiral. Therefore, the chain structures are formed by a hydrogen-bonded network between adjacent molecules with alternating adsorbed chirality. These chain structures accommodate longer alkyl tails through larger unit cells, while the position of the hydroxyl group within the alcohol molecule can produce denser unit cells that maximize intermolecular interactions. Interestingly, when intrinsic chirality is introduced into the molecule as in the case of 2-butanol, the assembly changes completely and square packing structures with chiral pockets are observed. This is rationalized by the fact that the intrinsic chirality of the molecule directs the chirality of the adsorbed hydroxyl group meaning that heterochiral chain structures cannot form. Overall this study provides a general framework for understanding the effect of simple alcohol molecular adstructures on hydrogen bonded aggregates and paves the way for rationalizing 2D chiral supramolecular assembly.

Assessment of van der Waals inclusive density functional theory methods for layered electroactive materials.

The discovery of computationally driven materials requires efficient and accurate methods. Density functional theory (DFT) meets these two requirements for many classes of materials. However, DFT-based methods have limitations. One significant shortcoming is the inadequate treatment of weak van der Waals (vdW) interactions, which are crucial for layered materials. Here we assess the performance of various vdW-inclusive DFT approaches for predicting the structure and voltage of layered electroactive materials for Li-ion batteries, considering a set of 20 different compounds. We find that the so-called optB86b-vdW density functional improves the agreement with the experimental data, closely followed by the latest generation of dispersion correction methods. These approaches yield average relative errors for the structural parameters smaller than 3%. The average deviations for redox potentials are below 0.15 V. Looking ahead, this study identifies accurate methods for Li-ion vdW bound systems, providing enhanced predictive power to DFT-assisted design for developing new types of electroactive materials in general.

Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer's Disease.

The mouse model of Alzheimer's disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossing Mt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by Mt1 overexpression throughout the cortex (Cx), which showed a prominent caudal-rostral gradient, and the hippocampus (HC). There was a trend for MT-1(/2) immunostaining to be increased in the areas surrounding the amyloid plaques in control male mice but not in Mt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of Mt1 overexpression were modest. However, in hippocampal western blots the microglial marker Iba-1 was increased in old male APPTgMT mice compared to APP-wild type (APPWT) mice, and the opposite was observed in young mice. Hippocampal CA1 neuronal loss was observed in Tg2576 mice, but was unaffected by Mt1 overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of Mt1 overexpression on the phenotype of Tg2576 mice here studied are modest.

Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4.

Nectin-4 is a tumor antigen present on the surface of breast, ovarian and lung carcinoma cells. It is rarely present in normal adult tissues and is therefore a candidate target for cancer immunotherapy. Here, we identified a Nectin-4 antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding to and off-rate from eight different HLA class I molecules. We then combined biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtained from healthy donors, that specifically lyzed HLA-A2(+) cells pulsed with 2 out of the 5 peptides, indicating the presence of anti-Nectin-4 CD8(+) T lymphocytes in the human T cell repertoire. Finally, an HLA-A2-restricted cytolytic T cell clone derived from a breast cancer patient recognized peptide Nectin-4145-153 (VLVPPLPSL) and lyzed HLA-A2(+) Nectin-4(+) breast carcinoma cells. These results indicate that peptide Nectin-4145-153 is naturally processed for recognition by T cells on HLA-A2 molecules. It could be used to monitor antitumor T cell responses or to immunize breast cancer patients.

Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker.

The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone.

Unveiling the electrochemical mechanisms of Li2Fe(SO4)2 polymorphs by neutron diffraction and density functional theory calculations.

The quest for new sustainable iron-based positive electrode materials for lithium-ion batteries recently led to the discovery of a new family of compounds with the general formula Li2M(SO4)2 with M = transition metal, which presents monoclinic and orthorhombic polymorphs. In terms of electrochemical performances, although both Li2Fe(SO4)2 polymorphs present a similar potential of ∼3.8 V vs. Li(+)/Li(0), the associated electrochemical processes drastically differ in terms of polarization and reaction redox mechanisms. We herein provide an explanation to account for such a behavior. While monoclinic Li2Fe(SO4)2 directly transforms into Li1.0Fe(SO4)2 upon oxidation, the orthorhombic counterpart forms a distinct intermediate Li1.5Fe(SO4)2 phase leading to a two-step delithiation process involving an unequal depopulation of the two Li sites pertaining to the structure as deduced by neutron powder diffraction experiments and confirmed by both density functional theory and Bond Valence Energy Landscape calculations. Moreover, to access band gap information, both polymorphs are studied by UV/Vis spectroscopy. Lastly, the possibility of transforming the monoclinic phase to the orthorhombic phase under pressure is explored.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol.

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopic understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule's intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network's enantioselective interaction with other molecules.

Dry Reforming of Methane on a Highly-Active Ni-CeO2 Catalyst: Effects of Metal-Support Interactions on C-H Bond Breaking.

Ni-CeO2 is a highly efficient, stable and non-expensive catalyst for methane dry reforming at relative low temperatures (700 K). The active phase of the catalyst consists of small nanoparticles of nickel dispersed on partially reduced ceria. Experiments of ambient pressure XPS indicate that methane dissociates on Ni/CeO2 at temperatures as low as 300 K, generating CHx and COx species on the surface of the catalyst. Strong metal-support interactions activate Ni for the dissociation of methane. The results of density-functional calculations show a drop in the effective barrier for methane activation from 0.9 eV on Ni(111) to only 0.15 eV on Ni/CeO2-x (111). At 700 K, under methane dry reforming conditions, no signals for adsorbed CHx or C species are detected in the C 1s XPS region. The reforming of methane proceeds in a clean and efficient way.