Engineering the defect distribution in ZnO nanorods through laser irradiation.

In recent years, defect engineering has shown great potential to improve the properties of metal oxide nanomaterials for various applications thus received extensive investigations. While traditional techniques mostly focus on controlling the defects during the synthesis of the material, laser irradiation has emerged as a promising post-deposition technique to further modulate the properties of defects yet there is still limited information. In this article, defects such as oxygen vacancies are tailored in ZnO nanorods through nanosecond (ns) laser irradiation. The relation between laser parameters and the temperature rise in the ZnO due to laser heating was established based on the observation in the SEM and the simulation. Raman spectra indicated that the concentration of the oxygen vacancies in the ZnO is temperature-dependent and can be controlled by changing the laser fluence and exposure time. This is also supported by the absorption spectra and the photoluminescence spectra of ZnO NRs irradiated under these conditions. On the other hand, the distribution of the oxygen vacancies was studied by XPS depth profiling, and it was confirmed that the surface-to-bulk ratio of the oxygen vacancies can be modulated by varying the laser fluence and exposure time. Based on these results, four distinctive regimes containing different ratios of surface-to-bulk oxygen vacancies have been identified. Laser-processed ZnO nanorods were also used as the catalyst for the photocatalytic degradation of rhodamine B (RhB) dye to demonstrate the efficacy of this laser engineering technique.

The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus.

Complement-dependent microglia pruning of excitatory synapses has been widely reported in physiological and pathological conditions, with few reports concerning pruning of inhibitory synapses or direct regulation of synaptic transmission by complement components. Here, we report that loss of CD59, an important endogenous inhibitor of the complement system, leads to compromised spatial memory performance. Furthermore, CD59 deficiency impairs GABAergic synaptic transmission in the hippocampal dentate gyrus (DG). This depends on regulation of GABA release triggered by Ca2+ influx through voltage-gated calcium channels (VGCCs) rather than inhibitory synaptic pruning by microglia. Notably, CD59 colocalizes with inhibitory pre-synaptic terminals and regulates SNARE complex assembly. Together, these results demonstrate that the complement regulator CD59 plays an important role in normal hippocampal function.

Identification of hub proteins in cerebrospinal fluid as potential biomarkers of Alzheimer's disease by integrated bioinformatics.

BACKGROUND: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with complex pathophysiology. Therefore, the identification of novel effective fluid biomarkers is essential for Alzheimer's disease diagnosis and drug development. This study aimed to identify potential candidate hub proteins in cerebrospinal fluid for precise Alzheimer's disease diagnosis using bioinformatics methods. METHODS: A total of 29 co-significant differentially expressed proteins were identified by differential protein expression analysis in four different cohorts. Functional enrichment analysis revealed that most of these proteins were enriched in pathways related to glycometabolism. Using the Least Absolute Shrinkage and Selection Operator (LASSO) and random forest feature selection methods, six hub proteins [14-3-3 protein zeta/delta (YWHAZ), SPARC-related modular calcium-binding protein 1 (SMOC1), aldolase A (ALDOA), pyruvate kinase isoenzyme type M2 (PKM), chitinase-3-like protein 1 (CHI3L1), and secreted phosphoprotein 1 (SPP1)] were identified. RESULTS: These six hub proteins were upregulated in the cerebrospinal fluid of patients with Alzheimer's disease compared with cognitively unimpaired control individuals. Meanwhile, SMOC1, ALDOA, and PKM were specifically upregulated in the cerebrospinal fluid of patients with Alzheimer's disease but not in other neurodegenerative diseases. Build AD diagnostic models showed that a single hub protein or six hub proteins combination had an excellent ability to discriminate Alzheimer's disease. CONCLUSIONS: In conclusion, our study suggests that these identified hub proteins, which are related to glycometabolism, may be potential biomarkers for further basic and clinical research in Alzheimer's disease.

Ag@Pd bimetallic structures for enhanced electrocatalytic CO2 conversion to CO: an interplay between the strain effect and ligand effect.

Electrochemical CO2 reduction reactions provide a promising path to effectively convert CO2 into valuable chemicals and fuels for industries. Among the many CO2 conversion catalysts, Pd stands out as a promising catalyst for effective CO2 to CO conversion. Here, using the misfit strain strategy, Ag@Pd bimetallic nanoparticles with different Pd overlayer contents were prepared as CO2 reduction catalysts. By varying the Pd overlayer content, all the Ag@Pd bimetallic nanoparticles exhibited superior CO2 conversion performance over their Pd and Ag nanoparticle counterparts. An optimal Pd-to-Ag ratio of 1.5 : 1 yielded the highest CO faradaic efficiency of 94.3% at -0.65 V vs. RHE with a high CO specific current density of 3.9 mA cm-2. It was found that the Pd content can substantially affect the interplay between the strain effect and ligand effect, resulting in optimized binding properties of the reaction intermediates on the catalyst surface, thereby enhancing the CO2 reduction performance.

Engineering surface segregation of perovskite oxide through wet exsolution for CO catalytic oxidation.

Cation segregation occurring near the surface or interfaces of solid catalysts plays an important role in catalytic reactions. Unfortunately, the native surface of perovskite oxides is dominated by passivated A-site segregation, which severely hampers the catalytic activity and durability of the system. To address this issue, herein, we present a wet exsolution method to reconstruct surface segregation in perovskite cobalt oxide. Under reduction etching treatment of glycol solution, inert surface Sr segregation was transformed into active Co3O4 segregation. By varying the reaction time, we achieved differing coverage of the active Co3O4 segregation on the La0.5Sr0.5CoO3-δ (LSCO) perovskite oxide surface. This study reveals that CO oxidation activity exhibits a volcano-shaped dependence on the coverage of Co3O4 segregation at the surface of a perovskite cobalt oxide. Furthermore, we find that a suitable coverage of Co3O4 segregation can dramatically improve the catalytic activity of the perovskite catalyst by enhancing interface interactions. Co K-edge, Co L-edge, and O K-edge X-ray absorption spectra confirm that the synergistic effect optimizes the covalence of the metal-oxygen bond at the surface and interface. This work not only contributes to the design and development of perovskite-type catalysts, but also provides important insight into the relationship between surface segregation and catalytic activity.

Activating Surface Lattice Oxygen of a Cu/Zn1-xCuxO Catalyst through Interface Interactions for CO Oxidation.

Surface lattice oxygen in metal oxides is a common participant in many chemical reactions. Given this, the structural design of catalysts to activate lattice oxygen and moreover investigations into the effect of lattice oxygen on reaction pathways are hot topics. With this in mind, herein we prepare CuO-Zn1-xCuxO (ZCO) nanofibers akin to the Trojan horse legend and via an in situ reduction obtain activated Cu/Zn1-xCuxO (Cu/ZCO) nanofibers. X-ray absorption spectroscopy and X-ray photoelectron spectroscopy reveal that surface lattice oxygen of Cu/ZCO is effectively activated from inert O2- to reactive O2-x. This activation stems from the enhanced covalence of metal-oxygen bonds and the electron transfer between Cu and the support. Online mass spectrometry reveals that Cu/ZCO with activated lattice oxygen exhibits a higher Mars-van Krevelen reaction efficiency during the CO oxidation process. This study offers a new avenue to engineer interface interactions, given, as highlighted here, the importance of surface lattice oxygen in oxide supports during the catalytic process.

Versatile memristor for memory and neuromorphic computing.

The memristor is a promising candidate to implement high-density memory and neuromorphic computing. Based on the characteristic retention time, memristors are classified into volatile and non-volatile types. However, a single memristor generally provides a specific function based on electronic performances, which poses roadblocks for further developing novel circuits. Versatile memristors exhibiting both volatile and non-volatile properties can provide multiple functions covering non-volatile memory and neuromorphic computing. In this work, a versatile memristor with volatile/non-volatile bifunctional properties was developed. Non-volatile functionality with a storage window of 4.0 × 105 was obtained. Meanwhile, the device can provide threshold volatile functionalities with a storage window of 7.0 × 104 and a rectification ratio of 4.0 × 104. The leaky integrate-and-fire (LIF) neuron model and artificial synapse based on the device have been studied. Such a versatile memristor enables non-volatile memory, selectors, artificial neurons, and artificial synapses, which will provide advantages regarding circuit simplification, fabrication processes, and manufacturing costs.

Two-dimensional materials for electrochemical CO2 reduction: materials, in situ/operando characterizations, and perspective.

Electrochemical CO2 reduction (CO2 ECR) is an efficient approach to achieving eco-friendly energy generation and environmental sustainability. This approach is capable of lowering the CO2 greenhouse gas concentration in the atmosphere while producing various valuable fuels and products. For catalytic CO2 ECR, two-dimensional (2D) materials stand as promising catalyst candidates due to their superior electrical conductivity, abundant dangling bonds, and tremendous amounts of surface active sites. On the other hand, the investigations on fundamental reaction mechanisms in CO2 ECR are highly demanded but usually require advanced in situ and operando multimodal characterizations. This review summarizes recent advances in the development, engineering, and structure-activity relationships of 2D materials for CO2 ECR. Furthermore, we overview state-of-the-art in situ and operando characterization techniques, which are used to investigate the catalytic reaction mechanisms with the spatial resolution from the micron-scale to the atomic scale, and with the temporal resolution from femtoseconds to seconds. Finally, we conclude this review by outlining challenges and opportunities for future development in this field.

Elevated ß-secretase 1 expression mediates CD4+ T cell dysfunction via PGE2 signalling in Alzheimer's disease.

Circulating CD4+ T cells are dysfunctional in Alzheimer's disease (AD), however, the underlying molecular mechanisms are not clear. In this study, we demonstrate that CD4+ T cells from AD patients and 5xFAD transgenic mice exhibit elevated levels of ß-secretase 1 (BACE1). Overexpression of BACE1 in CD4+ T cells potentiated CD4+ T-cell activation and T-cell-dependent immune responses. Mechanistically, BACE1 modulates prostaglandin E2 (PGE2) synthetase-microsomal prostaglandin E synthase 2 (mPGES2)-to promote mPGES2 maturation and PGE2 production, which increases T-cell receptor (TCR) signalling. Moreover, administration of peripheral PGE2 signalling antagonists partially ameliorates CD4+ T cell overactivation and AD pathology in 5xFAD mice. Overall, our results reveal a potential role for BACE1 in mediating CD4+ T-cell dysfunction in AD.

Fabrication of outstanding thermal-insulating, mechanical robust and superhydrophobic PP/CNT/sorbitol derivative nanocomposite foams for efficient oil/water separation.

Water pollution caused by industrial oily wastewater, is world-widely concerned by both scientific and practical researches, owing to its catastrophic destruction to natural environment, which highlights the urgency of producing green and advanced separation materials. Herein, a novel approach was proposed to fabricate oil-absorbing and oil/water-separating microcellular polypropylene (PP)/carbon nanotubes (CNTs)/sorbitol nanocomposites using a simple, green, and facile microcellular foaming technology. Owning to the effectively modified crystallization via introducing CNTs/sorbitol derivatives, the ultralight and highly-reticulated PP microcellular foam was prepared with an open-cell content of 99.4% and an expansion ratio of 50, which facilitated the creation of nano-porous structures on cell walls. Hence, the as-prepared PP nanocomposite foam presented pronounced absorption capacity of 40 g/g for applied oils with recovery efficiency of 97.2%, superior thermal-insulating and mechanical performance. Furthermore, the as-achieved unique hierarchical porous structures of the PP/CNT/sorbitol foam contributed to the outstanding oil/water separation capability, separation efficiency of up-to 97.6%, ascribed to its superhydrophobicity, capillary penetration action, high porosity and open-cell content. Therefore, this work provided new insight into the feasibility of advantageous, high-efficiency, environmentally friendly, and profitable PP-based foams as oil absorbents, which, to the best of our knowledge, outperform conventional polymer absorbents in treatment of oily wastewater.

Increased ß-site APP cleaving enzyme 1-mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear. METHODS: We measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor ß subunit (INSR-ß), and soluble INSR (sINSR) levels in a clinical cohort study. RESULTS: T2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR-ß, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR cleavage, which was associated with insulin resistance. DISCUSSION: The elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.

Tunable Tensile Properties of Polypropylene and Polyethylene Terephthalate Fibrillar Blends through Micro-/Nanolayered Extrusion Technology.

Fiber-reinforcement is a well-established technique to enhance the tensile properties of polymer composites, which is achieved via changing the reinforcing material concentration and orientation. However, the conventional method can be costly and may lead to poor compatibility issues. To overcome these challenges, we demonstrate the use of micro-/nanolayer (MNL) extrusion technology to tune the mechanical properties of polypropylene (PP)/polyethylene terephthalate (PET) fibrillar blends. PET nanofibers-in-PP microfiber composites, with 3, 7, and 15 wt.% PET, are first prepared using a spunbond system to induce high aspect-ratio PET nanofibers. The PP/PET fibers are then reprocessed in an MNL extrusion system and subjected to shear and extensional flow fields in the channels of the uniquely designed layer multipliers. Increasing the mass flow rate and number of multipliers is shown to orient the PET nanofibers along the machine direction (MD), as confirmed via scanning electron microscopy. Tensile tests reveal that up to a 45% and 46% enhancement in elastic modulus and yield strength are achieved owing to the highly aligned PET nanofibers along the MD under strongest processing conditions. Overall, the range of tensile properties obtained using MNL extrusion implies that the properties of fiber-reinforced composites can be further tuned by employing this processing technique.

Progranulin Administration Attenuates ß-Amyloid Deposition in the Hippocampus of 5xFAD Mice Through Modulating BACE1 Expression and Microglial Phagocytosis.

Loss of function mutations in the progranulin (PGRN) gene is a risk factor for Alzheimer's disease (AD). Previous works reported that the deficiency of PGRN accelerates ß-amyloid (Aß) accumulation in AD transgenic mouse brains while overexpression of PGRN could restrain disease progression. However, mechanisms of PGRN in protecting against Aß deposition remains unclear. Here, using the 5xFAD AD mouse model, we show that intrahippocampal injection of PGRN protein leads to a reduction of Aß plaques, downregulation of beta-secretase 1 (BACE1), and enhanced microglia Aß phagocytosis in the mouse hippocampus. Furthermore, PGRN treatment inhibited BACE1 expression in N2a cells and primary culture neurons and improved the phagocytic capacity of microglia isolated from 5xFAD mouse brains. Collectively, our results provide further evidence that enhancing progranulin could be a promising option for AD therapy.

Single-nucleus RNA sequencing reveals transcriptional changes of hippocampal neurons in APP23 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that mostly strikes the elderly. However, the exact molecular and cellular pathogenesis of AD, especially the dynamic changes of neurons during disease progression, remains poorly understood. Here we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional changes of hippocampal neurons in APP23 mouse model of AD. We performed snRNA-seq using a modified Smart-seq2 technique on 3,280 neuronal nuclei from the hippocampus of young and aged APP23 and control mice and identified four distinct subpopulations. Comparative transcriptional analysis showed multiple changes in different subtypes of hippocampal neurons of APP23 mice in comparison to control mice, as well as the transcriptional changes in these neurons during disease progression. Our findings revealed multiple neuronal subtype-specific transcriptional changes that may lead to targets for future studies of AD.

Ubiquitylome study identifies increased histone 2A ubiquitylation as an evolutionarily conserved aging biomarker.

The long-lived proteome constitutes a pool of exceptionally stable proteins with limited turnover. Previous studies on ubiquitin-mediated protein degradation primarily focused on relatively short-lived proteins; how ubiquitylation modifies the long-lived proteome and its regulatory effect on adult lifespan is unclear. Here we profile the age-dependent dynamics of long-lived proteomes in Drosophila by mass spectrometry using stable isotope switching coupled with antibody-enriched ubiquitylome analysis. Our data describe landscapes of long-lived proteins in somatic and reproductive tissues of Drosophila during adult lifespan, and reveal a preferential ubiquitylation of older long-lived proteins. We identify an age-modulated increase of ubiquitylation on long-lived histone 2A protein in Drosophila, which is evolutionarily conserved in mouse, monkey, and human. A reduction of ubiquitylated histone 2A in mutant flies is associated with longevity and healthy lifespan. Together, our data reveal an evolutionarily conserved biomarker of aging that links epigenetic modulation of the long-lived histone protein to lifespan.

Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B Cells and Elicit Antibody Recall Responses.

Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKTFH) cells and their interactions with memory B cells in recall responses. Generation of memory iNKTFH cells required lipid Ag presentation by dendritic cells but not by B cells. Upon rechallenge, memory iNKTFH cells recognized lipid Ags presented by memory B cells, which recalled iNKTFH effector cells and elicited B cell memory responses. However, LPS, which promoted the synthesis of self-lipids, failed to elicit recall responses in the absence of exogenous lipid Ags.

M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue.

Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages. With CD1d conditional knockout (KO) mice, we further demonstrated that natural killer T (NKT) cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice, whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization. Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.

Super-Resolution Imaging at Mid-Infrared Waveband in Graphene-nanocavity formed on meta-surface.

Plasmonic structured illumination microscopy (PSIM) is one of the promising wide filed optical imaging methods, which takes advantage of the surface plasmons to break the optical diffraction limit and thus to achieve a super-resolution optical image. To further improve the imaging resolution of PSIM, we propose in this work a so called graphene nanocavity on meta-surface structure (GNMS) to excite graphene surface plasmons with a deep sub-wavelength at mid-infrared waveband. It is found that surface plasmonic interference pattern with a period of around 52 nm can be achieved in graphene nanocavity formed on structured meta-surface for a 7 µm wavelength incident light. Moreover, the periodic plasmonic interference pattern can be tuned by simply changing the nanostructures fabricated on meta-surface for different application purposes. At last, the proposed GNMS structure is applied for super-resolution imaging in PSIM and it is found that an imaging resolution of 26 nm can be achieved, which is nearly 100 folds higher than that can be achieved by conventional epi-fluorescence microscopy. In comparison with visible waveband, mid-infrared is more gently and safe to biological cells and thus this work opens the new possibility for optical super-resolution imaging at mid-infrared waveband for biological research field.

TLR3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer T cells against enterovirus 71 infection.

Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT) cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs). Mechanistically, interleukin (IL)-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients.