Neurodegenerative pathways and metabolic changes in the hippocampus and cortex of mice exposed to urban particulate matter: Insights from an integrated interactome analysis.

Recently, urban particulate matter (UPM) exposure has been associated with the development of brain disorders. This study uses bioinformatic analyses to elucidate the molecular unexplored mechanisms underlying the effects of UPM exposure on the brain. Mice are exposed to UPM (from 3 days to 20 weeks), and their behavioral patterns measured. We measure pathology and gene expression in the hippocampus and cortical regions of the brain. An integrated interactome of genes is established, which enriches information on metabolic processes. Using this network, we isolate the core genes that are differentially expressed in the samples. We observe cognitive loss and pathological changes in the brains of mice at 16 or 20 weeks of exposure. Through network analysis of core-differential genes and measurement of pathway activity, we identify differences in the response to UPM exposure between the hippocampus and cortex. However, neurodegenerative disease pathways are implicated in both tissues following short-term exposure to UPM. There were also significant changes in metabolic function in both tissues depending on UPM exposure time. Additionally, the cortex of UPM-exposed mice shows more similarities with psychiatric disorders than with neurodegenerative diseases. The connectivity map database is used to isolate genes contributing to changes in expression due to UPM exposure. New approaches for inhibiting or preventing the brain damage caused by UPM exposure can be developed by targeting the functions and selected genes identified in this study.

Facet-Defined Dilute Metal Alloy Nanorods for Efficient Electroreduction of CO2 to n-Propanol.

Electroreduction of CO2 into liquid fuels is a compelling strategy for storing intermittent renewable energy. Here, we introduce a family of facet-defined dilute copper alloy nanocrystals as catalysts to improve the electrosynthesis of n-propanol from CO2 and H2O. We show that substituting a dilute amount of weak-CO-binding metals into the Cu(100) surface improves CO2-to-n-propanol activity and selectivity by modifying the electronic structure of catalysts to facilitate C1-C2 coupling while preserving the (100)-like 4-fold Cu ensembles which favor C1-C1 coupling. With the Au0.02Cu0.98 champion catalyst, we achieve an n-propanol Faradaic efficiency of 18.2 ± 0.3% at a low potential of -0.41 V versus the reversible hydrogen electrode and a peak production rate of 16.6 mA·cm-2. This study demonstrates that shape-controlled dilute-metal-alloy nanocrystals represent a new frontier in electrocatalyst design, and precise control of the host and minority metal distributions is crucial for elucidating structure-composition-property relationships and attaining superior catalytic performance.

Bimetallic copper palladium nanorods: plasmonic properties and palladium content effects.

Cu is an inexpensive alternative plasmonic metal with optical behaviour comparable to Au but with much poorer environmental stability. Alloying with a more stable metal can improve stability and add functionality, with potential effects on the plasmonic properties. Here we investigate the plasmonic behaviour of Cu nanorods and Cu-CuPd nanorods containing up to 46 mass percent Pd. Monochromated scanning transmission electron microscopy electron energy-loss spectroscopy first reveals the strong length dependence of multiple plasmonic modes in Cu nanorods, where the plasmon peaks redshift and narrow with increasing length. Next, we observe an increased damping (and increased linewidth) with increasing Pd content, accompanied by minimal frequency shift. These results are corroborated by and expanded upon with numerical simulations using the electron-driven discrete dipole approximation. This study indicates that adding Pd to nanostructures of Cu is a promising method to expand the scope of their plasmonic applications.

Ligand-Controlled Electroreduction of CO2 to Formate over Facet-Defined Bimetallic Sulfide Nanoplates.

CO2 reduction (CO2R) catalyzed by an efficient, stable, and earth-abundant electrocatalyst offers an attractive means to store energy derived from renewable sources. Here, we describe the synthesis of facet-defined Cu2SnS3 nanoplates and the ligand-controlled CO2R property. We show that thiocyanate-capped Cu2SnS3 nanoplates possess excellent selectivity toward formate over a wide range of potentials and current densities, attaining a maximum formate Faradaic efficiency of 92% and partial current densities as high as 181 mA cm-2 when tested using a flow cell with gas-diffusion electrode. In situ spectroscopic measurements and theoretical calculations reveal that the high formate selectivity originates from favorable adsorption of HCOO* intermediates on cationic Sn sites that are electronically modulated by thiocyanates bound to adjacent Cu sites. Our work illustrates that well-defined multimetallic sulfide nanocrystals with tailored surface chemistries could provide a new avenue for future CO2R electrocatalyst design.

Unraveling the Structural Sensitivity of CO2 Electroreduction at Facet-Defined Nanocrystals via Correlative Single-Entity and Macroelectrode Measurements.

The conversion of CO2 into value-added products is a compelling way of storing energy derived from intermittent renewable sources and can bring us closer to a closed-loop anthropogenic carbon cycle. The ability to synthesize nanocrystals of well-defined structure and composition has invigorated catalysis science with the promise of nanocrystals that selectively express the most favorable sites for efficient catalysis. The performance of nanocrystal catalysts for the CO2 reduction reaction (CO2RR) is typically evaluated with nanocrystal ensembles, which returns an averaged system-level response of complex catalyst-modified electrodes with each nanocrystal likely contributing a different (unknown) amount. Measurements at single nanocrystals, taken in the context of statistical analysis of a population, and comparison to macroscale measurements are necessary to untangle the complexity of the ever-present heterogeneity in nanocrystal catalysts, achieve true structure-property correlation, and potentially identify nanocrystals with outlier performance. Here, we employ environment-controlled scanning electrochemical cell microscopy to isolate and investigate the electrocatalytic CO2RR response of individual facet-defined gold nanocrystals. Using correlative microscopy approaches, we conclusively demonstrate that {110}-terminated gold rhombohedra possess superior activity and selectivity for CO2RR compared with {111}-terminated octahedra and high-index {310}-terminated truncated ditetragonal prisms, especially at low overpotentials where electrode kinetics is anticipated to dominate the current response. The methodology framework described here could inform future studies of complex electrocatalytic processes through correlative single-entity and macroscale measurement techniques.

Structural Diversity in Dimension-Controlled Assemblies of Tetrahedral Gold Nanocrystals.

Polyhedron packings have fascinated humans for centuries and continue to inspire scientists of modern disciplines. Despite extensive computer simulations and a handful of experimental investigations, understanding of the phase behaviors of synthetic tetrahedra has remained fragmentary largely due to the lack of tetrahedral building blocks with tunable size and versatile surface chemistry. Here, we report the remarkable richness of and complexity in dimension-controlled assemblies of gold nanotetrahedra. By tailoring nanocrystal interactions from long-range repulsive to hard-particle-like or to systems with short-ranged directional attractions through control of surface ligands and assembly conditions, nearly a dozen of two-dimensional and three-dimensional superstructures including the cubic diamond and hexagonal diamond polymorphs are selectively assembled. We further demonstrate multiply twinned icosahedral supracrystals by drying aqueous gold nanotetrahedra on a hydrophobic substrate. This study expands the toolbox of the superstructure by design using tetrahedral building blocks and could spur future computational and experimental work on self-assembly and phase behavior of anisotropic colloidal particles with tunable interactions.

Electrospray deposition for single nanoparticle studies.

Single entity electrochemical (SEE) studies that can probe activities and heterogeneity in activities at nanoscale require samples that contain single and isolated particles. Single, isolated nanoparticles are achieved here with electrospray deposition of colloidal nanoparticle solutions, with simple instrumentation. Role of three electrospray (ES) parameters, viz. spray distance (emitter tip-to-substrate distance), ES current and emitter tip diameter, in the ES deposition of single Au nano-octahedra (Au ODs) is examined. The ES deposition of single, isolated Au ODs are analyzed in terms of percentage of single NPs and local surface density of deposition. The local surface density of ES deposition of single Au ODs was found to increase with decrease in spray distance and emitter tip diameter, and increase in ES current. While the percentage of single particle ES deposition increased with increase in spray distance and decrease in emitter tip size. No significant change in the single Au ODs ES deposition percentage was observed with change in ES current values included in this study. The most favourable conditions in the ES deposition of Au ODs in this study resulted in the local surface density of 0.26 ± 0.05 single particles per µm2 and observation of 96.3% single Au OD deposition.

Kinetically Controlled Self-Assembly of Binary Polymer-Grafted Nanocrystals into Ordered Superstructures via Solvent Vapor Annealing.

Polymer-inorganic nanocomposites based on polymer-grafted nanocrystals (PGNCs) are enabling technologically relevant applications owing to their unique physical, chemical, and mechanical properties. While diverse PGNC superstructures have been realized through evaporation-driven self-assembly, this approach presents multifaceted challenges in experimentally probing and controlling assembly kinetics. Here, we report a kinetically controlled assembly of binary superstructures from a homogeneous disordered PGNC mixture utilizing solvent vapor annealing (SVA). Using a NaZn13-type superstructure as a model system, we demonstrate that varying the solvent vapor pressure during SVA allows for exquisite control of the rate and extent of PGNC assembly, providing access to nearly complete kinetic pathways of binary PGNC crystallization. Characterization of kinetically arrested intermediates reveals that assembly follows a multistep crystallization pathway involving spinodal-like preordering of PGNCs prior to NaZn13 nucleation. Our work opens up new avenues for the synthesis of multicomponent PGNC superstructures exhibiting multifunctionalities and emergent properties through a thorough understanding of kinetic pathways.

Characterization of Ligand Adsorption at Individual Gold Nanocubes.

Cetyltrimethylammonium bromide (CTAB) is a widely used surfactant that aids the aqueous synthesis of colloidal nanoparticles. However, the presence of residual CTAB on nanoparticle surfaces can significantly impact nanoparticle applications, such as catalysis and sensing, under hydrated conditions. As such, consideration of the presence and quantity of CTAB on nanoparticle surfaces under hydrated conditions is of significance. Herein, as part of an integrated material characterization framework, we demonstrate the feasibility of in situ atomic force microscopy (AFM) to detect CTAB on the surface of Au nanocubes (Au NCs) under hydrated conditions, which enabled superior characterization compared to conventional spectroscopic methods. In situ force-distance (FD) spectroscopy and Kelvin probe force microscopy (KPFM) measurements support additional characterization of adsorbed CTAB, while correlative in situ AFM and scanning electron microscopy (SEM) measurements were used to evaluate sequential steps of CTAB removal from Au NCs across hydrated and dehydrated environments, respectively. Notably, a substantial quantity of CTAB remained on the Au NC surface after methanol washing, which was detected in AFM measurements but was not detected in infrared spectroscopy measurements. Subsequent electrochemical cleaning was found to be critically important to remove CTAB from the Au NC surface. Correlative measurements were also performed on individual nanoparticles, which further validate the method described here as a powerful tool to determine the extent and degree of CTAB removal from nanoparticle surfaces. This AFM-based method is broadly applicable to characterize the presence and removal of ligands from nanomaterial surfaces under hydrated conditions.

Ficus erecta Thunb. Leaves Ameliorate Cognitive Deficit and Neuronal Damage in a Mouse Model of Amyloid-ß-Induced Alzheimer's Disease.

Alzheimer's disease (AD) pathogenesis is linked to amyloid plaque accumulation, neuronal loss, and brain inflammation. Ficus erecta Thunb. is a food and medicinal plant used to treat inflammatory diseases. Here, we investigated the neuroprotective effects of F. erecta Thunb. against cognitive deficit and neuronal damage in a mouse model of amyloid-ß (Aß)-induced AD. First, we confirmed the inhibitory effects of ethanol extracts of F. erecta (EEFE) leaves on Aß aggregation in vivo and in vitro. Next, behavioral tests (passive avoidance task and Morris water maze test) revealed EEFE markedly improved cognitive impairment in Aß-injected mice. Furthermore, EEFE reduced neuronal loss and the expression of neuronal nuclei (NeuN), a neuronal marker, in brain tissues of Aß-injected mice. EEFE significantly reversed Aß-induced suppression of cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression, indicating neuroprotection was mediated by the CREB/BDNF signaling. Moreover, EEFE significantly suppressed the inflammatory cytokines interleukin 1beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), and expression of ionized calcium-binding adaptor molecule 1 (Iba-1), a marker of microglial activation, in brain tissues of Aß-injected mice, suggesting anti-neuroinflammatory effects. Taken together, EEFE protects against cognitive deficit and neuronal damage in AD-like mice via activation of the CREB/BDNF signaling and upregulation of the inflammatory cytokines.

Ficus erecta Thunb Leaves Alleviate Memory Loss Induced by Scopolamine in Mice via Regulation of Oxidative Stress and Cholinergic System.

We examined the neuropharmacological effects of ethanol extract of Ficus erecta Thunb leaves (EEFE) on cognitive dysfunction in a scopolamine (SCO)-induced memory impairment animal model. Memory impairment was measured using the Y-maze test and passive avoidance task (PAT). For 19 days, EEFE (100 or 200 mg/kg) was treated through oral administration. Treatment with EEFE ameliorated memory impairment in behavioral tests, along with significant protection from neuronal oxidative stress and neuronal cell loss in the brain tissues of SCO-injected mice. Antioxidant and neuroprotective effects of EEFE were further confirmed using in vitro assays. Our findings indicate that the mechanisms of neuroprotection and antioxidation of EEFE are regulated by the cholinergic system, promotion of cAMP response element-binding protein (CREB) phosphorylation, and the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling activation. The current study proposes that EEFE could be an encouraging plant resource and serve as a potent neuropharmacological drug candidate against neurodegenerative diseases.

Korean traditional herbal formula Soshiho-tang attenuates memory impairment and neuronal damage in mice with amyloid-beta-induced Alzheimer's disease.

BACKGROUND: Soshiho-tang (SST), also known as Xiaochaihu-tang in China and Sho-saiko-to in Japan, is an Oriental herbal formula traditionally used to treat febrile diseases. Recently, several in vitro and in vivo studies have reported the anti-cancer, anti-liver disease, and anti-inflammatory activities of SST. However, there is little evidence of its effects on neurological diseases. We previously reported the inhibitory effects of SST on in vitro acetylcholinesterase (AChE) activation and amyloid-ß (Aß) aggregation, which are crucial hallmarks of Alzheimer's disease (AD). In the present study, we report that SST has preventive effects on memory impairment and neuronal cell changes in an Aß-induced AD-like mouse model. METHODS: Male mice underwent injection of Aß aggregates and administered SST (500, 1,000, or 2,000 mg/kg/day) for 20 days. Behavioral tests (passive avoidance task [PAT] and Morris water maze [MWM] test) were conducted. Lastly, brain sections were obtained from sacrificed mice for quantitative analysis. RESULTS: Intracerebroventricular (ICV) injection of Aß aggregates significantly decreased the latency time in the PAT and MWM test compared to normal control. In contrast, SST administration markedly reversed the latency caused by Aß injection. Additionally, our data revealed that SST-mediated improvements in memory impairment are related to its neuroprotective and anti-neuroinflammatory effects. On histological analysis, SST treatment protected neuronal loss and damage as well as microglial activation, and ameliorated amount of Aß in brain of mouse model of AD. CONCLUSION: Our findings suggest that SST may be a promising candidate for the development of novel drugs for AD.

Simultaneous Quantification of Four Marker Compounds in Bauhinia coccinea Extract and Their Potential Inhibitory Effects on Alzheimer's Disease Biomarkers.

Bauhinia coccinea is a tropical woody plant widely distributed in Vietnam and Unnan in southern China. Although many studies have shown the biological activities of extracts from various other species in the genus, no studies have investigated the effects of B. coccinea extracts on biological systems. In the present study, a quantitative analysis of four marker compounds of ethanol extracts of B. coccinea branches (EEBC) was performed using the high performance liquid chromatography (HPLC)-photodiode array (PDA) method. Among gallic acid, (+)-catechin, ellagic acid, and quercitrin contained in EEBC, the most abundant compound was (+)-catechin (18.736 mg/g). In addition, we investigated the EEBC on neuroprotection, antioxidation, and Alzheimer's disease (AD) marker molecules, acetylcholinesterase (AChE), and amyloid-ß (Aß). EEBC significantly inhibited hydrogen peroxide (H2O2)-induced cell death in a HT22 neuronal cell line and increased 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl scavenging activity markedly. EEBC also inhibited AChE and Aß aggregation. Among the four compounds, gallic acid exhibited strong inhibitory effects against AChE activation. In the Aß aggregation assay, the four marker compounds exhibited inhibitory effects lower than 30%. According to the results, EEBC could exert anti-AChE activation and Aß aggregation activities based on the interactive effects of the marker compounds. Our findings suggest that EEBC are sources of therapeutic candidates for application in the development of AD medication based on AChE and Aß dual targeting.

Catechol-Type Flavonoids from the Branches of Elaeagnus glabra f. oxyphylla Exert Antioxidant Activity and an Inhibitory Effect on Amyloid-ß Aggregation.

Elaeagnus glabra f. oxyphylla (Elaeagnaceae) is a small evergreen tree with narrow lanceolate leaves that is native to Korea. In this work, we studied the chemical composition of E. glabra f. oxyphylla branches (EGFOB) for the first time. Additionally, we evaluated the effects of the ethanol extract of EGFOB and each of its chemical components on key mediators of Alzheimer's disease (AD), namely, amyloid-ß (Aß) aggregation and oxidative stress. The ethanol extract of EGFOB decreased Aß aggregation (IC50 = 32.01 µg/mL) and the levels of the oxidative free radicals 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 11.35 and 12.32 µg/mL, respectively). Sixteen compounds were isolated from EGFOB. Among them, procyanidin B3 (8), procyanidin B4 (9), and helichrysoside (13) significantly inhibited Aß aggregation (IC50 = 14.59, 32.64, and 44.45 µM, respectively), indicating their potential as bioactive compounds to control Aß aggregation. Furthermore, these compounds markedly enhanced in vitro scavenging activity against ABTS (IC50 = 3.21-4.61 µM). In the DPPH test, they showed lower scavenging activity than in the ABTS test (IC50 ≥ 54.88 µM). Thus, these results suggest that EGFOB and specifically compounds 8, 9, and 13 may be beneficial in AD prevention and treatment through their antioxidant and anti-Aß aggregation activities.

Heterometallic Seed-Mediated Growth of Monodisperse Colloidal Copper Nanorods with Widely Tunable Plasmonic Resonances.

We report a heterometallic seed-mediated synthesis method for monodisperse penta-twinned Cu nanorods using Au nanocrystals as seeds. Elemental analyses indicate that resultant nanorods consist predominantly of copper with a gold content typically below 3 atom %. The nanorod aspect ratio can be readily adjusted from 2.8 to 13.1 by varying the molar ratio between Au seeds and Cu precursor, resulting in narrow longitudinal plasmon resonances tunable from 762 to 2201 nm. Studies of reaction intermediates reveal that symmetry-breaking is promoted by rapid nanoscale diffusion in Au-Cu alloys and the formation of a gold-rich surface. The growth pathway features coevolving shape and composition whereby nanocrystals become progressively enriched with Cu concomitant with nanorod growth. The availability of uniform colloidal Cu nanorods with widely tunable aspect ratios opens new avenues toward the synthesis of derivative one-dimensional metal nanostructures, and applications in surface-enhanced spectroscopy, bioimaging, and electrocatalysis, among others.

Colloidal Synthesis of Nanohelices via Bilayer Lattice Misfit.

Helical structures are ubiquitous in natural and synthetic materials across multiple length scales. Excellent and sometimes unusual chiral optical, mechanical, and sensing properties have been previously demonstrated in such symmetry-breaking shape, yet a general principle to realize helical structures at the sub-100 nm scale via colloidal synthesis remains underexplored. In this work, we describe the wet-chemical synthesis of monodisperse nanohelices based on gadolinium oxide (Gd2O3). Aberration-corrected electron microscopy revealed that individual nanohelices consist of a bilayer structure with the outer and inner layers derived from the {111} and {100} planes of bulk Gd2O3, respectively. Distinct from existing inorganic nanocoils with flexible bending geometries, the built-in lattice misfit between two adjacent crystal planes induces continuous helical growth yielding three-dimensional rigid nanohelices. Furthermore, the presence of water in the reaction was found to suppress the formation of nanohelices, producing nanoplates expressing predominantly {111} planes. Our study not only provides a bottom-up synthetic route and mechanistic understanding of nanohelices formation but may also open up new possibilities for creating chiral plasmonic nanostructures, luminescent biological labels, and nanoscale transducers.

Broadband Tunable Mid-infrared Plasmon Resonances in Cadmium Oxide Nanocrystals Induced by Size-Dependent Nonstoichiometry.

A central theme of nanocrystal (NC) research involves synthesis of dimension-controlled NCs and studyof size-dependent scaling laws governing their optical, electrical, magnetic, and thermodynamic properties. Here, we describe the synthesis of monodisperse CdO NCs that exhibit high quality-factor (up to 5.5) mid-infrared (MIR) localized surface plasmon resonances (LSPR) and elucidate the inverse scaling relationship between carrier concentration and NC size. The LSPR wavelength is readily tunable between 2.4 and ∼6.0 µm by controlling the size of CdO NCs. Structural and spectroscopic characterization provide strong evidence that free electrons primarily originate from self-doping due to NC surface-induced nonstoichiometry. The ability to probe and to control NC stoichiometry and intrinsic defects will pave the way toward predictive synthesis of doped NCs with desirable LSPR characteristics.

Similarity of therapeutic networks induced by a multi-component herbal remedy, Ukgansan, in neurovascular unit cells.

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer's disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. Here, we examined the therapeutic effects of Ukgansan (UGS), an herbal remedy with multi-targeting capabilities, using in vitro neurovascular unit models and an in vivo model of AD. In addition, we compared the therapeutic networks induced by UGS and its components in different neurovascular cell types. We found that UGS and its components protected neurovascular cells against diverse damaging agents and improved the behavioral patterns of AD model mice. A comparison of UGS- or its components-induced therapeutic networks, constructed from high-throughput data on gene expression, pathway activity, and protein phosphorylation, revealed similarities among neurovascular cell types, especially between BV-2 microglia and HBVP (human brain vascular pericytes). These findings, together with the functional connections between neurovascular cells, can explain the therapeutic effects of UGS. Furthermore, they suggest underlying similarities in the therapeutic mechanisms in different neurovascular cell types.

Probing Single-Particle Electrocatalytic Activity at Facet-Controlled Gold Nanocrystals.

Electrocatalytic reduction reactions (i.e., the hydrogen evolution reaction (HER) and oxygen reduction reaction) at individual, faceted Au nanocubes (NCs) and nano-octahedra (ODs) expressing predominantly {100} and {111} crystal planes on the surface, respectively, were studied by nanoscale voltammetric mapping. Cyclic voltammograms were collected at individual nanoparticles (NPs) with scanning electrochemical cell microscopy (SECCM) and correlated with particle morphology imaged by electron microscopy. Nanoscale measurements from a statistically informative set of individual NPs revealed that Au NCs have superior HER electrocatalytic activity compared to that of Au ODs, in good agreement with macroscale cyclic voltammetry measurements. Au NCs exhibited more particle-to-particle variation in catalytic activity compared to that with Au ODs. The approach of single-particle SECCM imaging coupled with macroscale CV on well-defined NPs provides a powerful toolset for the design and activity assessment of nanoscale electrocatalysts.