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All-solid-state sodium-ion batteries (ASS-SIBs) have great potential for application to large-scale energy storage devices due to their safety advantages, which are avoiding flammable organics and the abundance of sodium. In this study, plasma spraying was used to deposit Na 3 Zr 2 Si 2 PO 12 (NZSP) electrolyte to assemble high-performance ASS-SIBs. NZSP electrolyte layers were deposited at different spray conditions using NZSP powders in various particle sizes. The factors influencing the microstructure and compositions of NZSP layers were examined by characterizing the compositions of splat and cross-sectional microstructures of the deposits. It was found that the preferential evaporation loss of Na and P elements occurs severely to result in a large composition deviation from initial powders and spray particle size is a key factor that dominates their evaporation loss. The APS NZSP electrolytes present a dense microstructure, which is attributed to the low melting point of NZSP. The apparent porosity of the as-sprayed NZSPs was lower than 3%. The effect of annealing on the microstructure of APS NZSP was also investigated. With the increase in annealing temperature, the conductivity of the electrolyte increased and reached 1.93 × 10 −4 S/cm for F-NZSP-1000 °C at 200 °C.

Alkaline water electrolysis (AWE) for highly efficient hydrogen production requires a highly active cathode. In this work, the porous NiAlMo electrodes were prepared by plasma spraying of NiAlMo and Al powders with a dual-channel powder feeding strategy. The bilayer-structured electrode consisting of a NiAlMo bond coat and a NiAlMo-Al composite coating on the top was designed. Al particles in the composite coating were used as pore former. The effect of Al powder feeding off-set distance on the molten state of Al was examined for optimizing the pore structure. The activated NiAlMo-40Al/NiAlMo electrode exhibited an apparent porosity of 36.8% and a surface roughness of Ra 12.18 μm, with an overpotential of 34.22 mV at 10 mA cm −2 and a Tafel slope of 27.71 mV dec −1 , which was much lower than that of traditional NiAlMo electrodes. After a CP test for 10 h, the electrode remained intact and showed a stable overpotential of -0.34 V.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy. TREM2 is a genetic risk factor for Alzheimer’s disease, and soluble TREM2 (sTREM2) in the CSF correlates with AD progression. Here the authors study the role of sTREM2 in a mouse model of Alzheimer’s disease, and find it reduces amyloid accumulation and increases the numbers of plaque-associated microglia which correlates with improved behavioural function in the mice.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages. TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming. Interestingly, TREM2 exists both in its membrane-bound form and as a soluble variant (sTREM2), that latter is generated through proteolytic shedding or alternative splicing and can be detected in cerebrospinal fluid and plasma. Emerging clinical and preclinical evidence underscores the potential of TREM2 and sTREM2 as diagnostic biomarkers and therapeutic targets in Alzheimer’s disease (AD). This review provides a comprehensive overview of the molecular functions, regulatory mechanisms, and pathological implications of TREM2 and sTREM2 in AD. Furthermore, we explore their potential roles in diagnostics and therapeutics while suggesting key research directions for advancing TREM2/sTREM2-based strategies in combating AD.

Background TREM2 is an innate immune receptor specifically expressed in microglia. Coding variations in TREM2 have been reported to increase the risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. While multiple studies support a role for TREM2 in microglial recruitment to amyloid plaques, the chemoattractant factor modulating TREM2-dependent microglial responses has not been defined. Methods Potential binding of oligomeric amyloid-β 1–42 (oAβ 1–42 ) to TREM2 was tested by complementary approaches including solid phase binding, surface plasmon resonance and immunoprecipitation assays. The ability of oAβ 1–42 to activate TREM2 signaling pathways was examined by analyzing the phosphorylation of Syk and Akt in primary microglia as well as TREM2-mediated signaling in a reporter cell system. Lastly, the functional outcome of oAβ 1–42 -TREM2 interaction was tested by examining impacts on microglial migration in vitro and clustering around oAβ 1–42 -bearing brain areas in vivo. Results We found that oAβ 1–42 bound to TREM2 with high affinity and activated TREM2-dependent signaling pathway. Neither monomeric nor scrambled Aβ bound to TREM2 supporting a specific interaction between oAβ and TREM2. The disease-associated mutations of TREM2 reduced its binding affinity to oAβ 1–42 . Furthermore, we identified several positively charged amino acids within residues 31–91 of TREM2 that were crucial for its interaction with oAβ 1–42 . Importantly, oAβ 1–42 promoted microglial migration in vitro and clustering in vivo in a TREM2-dependent manner. Conclusions Our data establish a critical link between oAβ 1–42 , a major pathological component of AD, and TREM2, a strong genetic risk factor for AD expressed in microglia, and suggest that such interaction contributes to the pathogenic events in AD by modulating microglial responses.

Background The colony-stimulating factor 1 receptor (CSF1R) is a receptor tyrosine kinase essential for microglial development and homeostasis. While dysregulated CSF1R signaling has been implicated in Alzheimer’s disease (AD), the biological function of its soluble ectodomain (sCSF1R)—generated by a disintegrin and metalloproteinase 17 (ADAM17)-mediated cleavage—remains poorly understood in neurodegeneration. Methods We quantified sCSF1R levels in the brain and cerebrospinal fluid (CSF) of 5×FAD transgenic mice and wild-type controls using ELISA and immunoblotting, and reanalyzed publicly available CSF proteomic datasets from three independent, clinically characterized AD cohorts. Functional studies were performed in primary microglial cultures and through hippocampal delivery of recombinant sCSF1R into 5×FAD mice to evaluate its effects on microglial activity and amyloid pathology. Results In this study, we identify sCSF1R as a previously unrecognized, functionally active modulator of microglial responses in AD. Analysis of three independent clinical cohorts revealed significantly elevated sCSF1R levels in the CSF of AD patients, a finding recapitulated in both the brain and CSF of 5×FAD transgenic mice. Importantly, sCSF1R concentrations showed positive correlations with core AD biomarkers—including total tau, phosphorylated tau, and β-amyloid 1–42 (Aβ42)—and with measures of cognitive performance, highlighting its clinical significance and suggesting that sCSF1R may serve as a marker of disease-associated microglial responses. Functionally, recombinant sCSF1R enhanced microglial survival, migration, proinflammatory signaling, and Aβ phagocytosis in vitro. In vivo, administration of sCSF1R promoted microglial clustering around amyloid plaques, reduced Aβ deposition, and attenuated plaque-associated neuritic dystrophy in 5×FAD mice. Finally, we found that soluble TREM2 (sTREM2)—a CSF biomarker and potent activator of microglia—stimulates ADAM17-dependent cleavage of membrane-bound CSF1R, thereby driving the generation of sCSF1R. Collectively, these findings establish sCSF1R as a novel regulator of microglial function in AD and reveal a regulatory axis linking sTREM2, ADAM17 activity, and CSF1R shedding with potential implications for disease modulation. Conclusions These findings identify sCSF1R as a novel component of the neuroimmune signaling network in AD and highlight its dual potential as a CSF biomarker of beneficial microglial activation and a candidate therapeutic modulator of neuroinflammation and amyloid pathology.

It is traditionally believed that cerebral amyloid-beta (Aβ) deposits are derived from the brain itself in Alzheimer’s disease (AD). Peripheral cells such as blood cells also produce Aβ. The role of peripherally produced Aβ in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aβ to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aβ in the blood, and caused AD phenotypes including Aβ plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aβ levels, and alleviated brain Aβ burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aβ plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aβ can decrease brain Aβ deposition and represents a novel therapeutic approach for AD.

Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection, often leading to cognitive impairments. Growing evidence shows that artemisinin, an antimalarial drug, possesses potent anti-inflammatory and immunoregulatory activities. In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms. Mice were injected with LPS (750 μg · kg −1  · d −1 , ip, for 7 days) to establish an animal model of sepsis. Artemisinin (30 mg · kg −1  · d −1 , ip) was administered starting 4 days prior LPS injection and lasting to the end of LPS injection. We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests, attenuated neuronal damage and microglial activation in the hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of artemisinin (40 μΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6) and suppressed microglial migration. Furthermore, we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway; knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells. In conclusion, atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.

Alzheimer’s disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

The genome sequences of 175 Ebola virus from five districts in Sierra Leone, collected during September–November 2014, show that the rate of virus evolution seems to be similar to that observed during previous outbreaks and that the genetic diversity of the virus has increased substantially, with the emergence of several novel lineages. Increasing viral diversity of Ebola virus Wu-Chun Cao and colleagues report on how EBOV, the Ebola virus responsible for the ongoing epidemic in West Africa, has evolved. The authors describe 175 EBOV full-length genome sequences from five districts in Sierra Leone, collected between 28 September and 11 November 2014. They find a rate of virus evolution similar to that observed during previous EBOV outbreaks. The genetic diversity of the virus has increased substantially, with the emergence of several novel lineages. The sharp increase in genetic diversity underlines the importance of EBOV surveillance in Sierra Leone, Guinea and Liberia. A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths 1 , 2 . Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir 3 followed by sustained human-to-human infections 4 . It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics 5 , 6 . However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase 7 . Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10 −3 substitutions per site per year (95% highest posterior density interval, 1.04 × 10 −3 to 1.41 × 10 −3 substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.