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1.
Chem Soc Rev ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475099

RESUMO

Porphyrin-based frameworks, as specific kinds of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have been widely used in energy-related conversion processes, including the oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and CO2 reduction reaction (CO2RR), and also in energy-related storage technologies such as rechargeable Zn-air batteries. This review starts by summarizing typical crystal structures, molecular building blocks, and common synthetic procedures of various porphyrin-based frameworks used in energy-related technologies. Then, a brief introduction is provided and representative applications of porphyrin-based frameworks in ORR, OER, Zn-air batteries, and CO2RR are discussed. The performance comparison of these porphyrin-based frameworks in each field is also summarized and discussed, which pinpoints a clear structure-activity relationship. In addition to utilizing highly active porphyrin units for catalytic conversions, regulating the porous structures of porphyrin-based frameworks will enhance mass transfer and growing porphyrin-based frameworks on conductive supports will accelerate electron transfer, which will result in the improvement of the electrocatalytic performance. This review is therefore valuable for the rational design of more efficient porphyrin-based framework catalytic systems in energy-related conversion and storage technologies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33484092

RESUMO

Synthesizing molecule@support hybrids is appealing to improve molecular electrocatalysis. We report herein metal-organic framework (MOF)-supported Co porphyrins for the oxygen reduction reaction (ORR) with improved activity and selectivity. Co porphyrins can be grafted on MOF surfaces through ligand exchange. A variety of porphyrin@MOF hybrids were made using this method. Grafted Co porphyrins showed boosted ORR activity with large (> 70 mV) anodic shift of the half-wave potential compared to ungrafted porphyrins. By using active MOFs for peroxide reduction, the number of electrons transferred per O 2  increased from 2.65 to 3.70, showing significantly improved selectivity for the 4e ORR. We demonstrated that H 2 O 2  generated from O 2  reduction at Co porphyrins is further reduced at MOF surfaces, leading to improved 4e ORR. As a practical demonstration, these hybrids were used as air electrode catalysts in Zn-air batteries, which exhibited equal performance to that with Pt-based materials.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33462971

RESUMO

Nature uses Fe porphyrin sites for the oxygen reduction reaction (ORR). Synthetic Fe porphyrins have been extensively studied as ORR catalysts, but activity improvement is required. On the other hand, Fe porphyrins have been rarely shown to be efficient for the oxygen evolution reaction (OER). We herein report an   enzyme-inspired Fe  porphyrin   1 as an efficient catalyst for both ORR and OER. Complex  1 , which bears a tethered imidazole for Fe binding, beats imidazole-free analogue  2 , with an anodic shift of ORR half-wave potential by 160 mV and a decrease of OER overpotential by 150 mV to get the benchmark current density at 10 mA/cm 2 . Theoretical studies suggested that hydroxide attack to a formal Fe V =O form the O-O bond. The axial imidazole can prevent the formation of  trans  HO-Fe V =O, which is less effective to form O-O bond with hydroxide. As a practical demonstration, we assembled rechargeable Zn-air battery with  1 , which shows equal performance to that with Pt/Ir-based materials .

4.
J Phys Chem Lett ; : 758-763, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405930

RESUMO

Enhancing the gating performance of single-molecule conductance is significant for realizing molecular transistors. Herein, we report a new strategy to improve the electrochemical gating efficiency of single-molecule conductance with fused molecular structures consisting of heterocyclic rings of furan, thiophene, or selenophene. One order magnitude of gating ratio is achieved within a potential window of 1.2 V for the selenophene-based molecule, which is significantly greater than that of other heterocyclic and benzene ring molecules. This is caused by the different electronic structures of heterocyclic molecules and transmission coefficients T(E), and preliminary resonance tunneling is achieved through the highest occupied molecular orbital at high potential. The current work experimentally shows that electrochemical gating performance can be significantly modulated by the alignment of the conducting orbital of the heterocyclic molecule relative to the metal Fermi energy.

5.
Ecotoxicol Environ Saf ; 207: 111511, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254391

RESUMO

Decidualization, which endows the endometrium competency to adopt developing embryo and maintain appropriate milieu for following growth, is a pivotal process for human pregnancy. The delicate collaboration between ovarian steroid hormones estrogen and progesterone governs the process of decidualization and subsequent establishment of embryo implantation. Mycotoxin zearalenone (ZEA) is well known as endocrine disruptor due to its potent estrogenic activity. In this study, we investigated effects of ZEA on decidualization of human endometrial stromal cells. Results indicated that ZEA exhibited its inhibitory action through nuclear translocation of ERα. ZEA exposure led to dampened progress of decidualization, which could be attenuated by estrogen receptor antagonist. Notably, resveratrol (RSV) administration restored impaired decidualization process by induction of anti-oxidative gene glutathione peroxidase 3 (GPX3). This study provides novel insights into the mechanism underlying adverse effects of ZEA in human decidual stromal cells and suggests RSV a potential therapeutic candidate to alleviate ZEA-induced cytotoxicity during decidualization.


Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia , Zearalenona/toxicidade , Células Cultivadas , Decídua/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Receptor alfa de Estrogênio , Estrogênios/farmacologia , Feminino , Humanos , Gravidez , Progesterona/farmacologia , Células Estromais/efeitos dos fármacos
6.
Life Sci ; 266: 118905, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33333051

RESUMO

AIMS: Ferroptosis is involved in the pathogenesis of spinal cord injury (SCI). Carnosic acid (CA) is a natural phenolic diterpene, which possesses diversiform activities. However, whether the protective effect of CA on SCI is partly due to inhibition of ferroptosis was seldom investigated. Therefore, the objective of this study aimed to investigate the role of CA on ferroptosis in PC12 cells and the underlying mechanisms. MAIN METHODS: Cell viability, malondialdehyde (MDA) contents, glutathione (GSH) levels, and iron levels were detected to identify the construction of ferroptosis model in PC12 cell induced by erastin. The safe concentrations of CA on PC12 cells were measured via cell counting kit-8 (CCK-8) assays. Then, cellular MDA contents, GSH levels, iron levels, reactive species (RS) generation, and mitochondrial morphology were tested to determine the influence of CA on ferroptosis in erastin-treated PC12 cells. In addition, Western blot and RT-qPCR were utilized to detecteddetect the ferroptosis-related genes and proteins expression levels. KEY FINDINGS: Our study indicated that treatment with CA could reversed the increased MDA, iron, and RS levels, as well as the decreased GSH levels in erastin-treated PC12 cells. The protective effect of CA could be blocked by ML385. The inhibitory effect of CA on ferroptosis probably was partially governed by activation of Nrf2 to regulate the GSH synthesis and metabolism and cellular iron homeostasis. SIGNIFICANCE: CA can inhibit ferroptosis in PC12 cells induced by erastin via activating Nrf2 pathway, indicating that CA could lead to neuroprotective effect by restraining the occurrence of ferroptosis.

7.
Entropy (Basel) ; 22(9)2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-33286708

RESUMO

Despite many studies reporting hemispheric asymmetry in the representation and processing of emotions, the essence of the asymmetry remains controversial. Brain network analysis based on electroencephalography (EEG) is a useful biological method to study brain function. Here, EEG data were recorded while participants watched different emotional videos. According to the videos' emotional categories, the data were divided into four categories: high arousal high valence (HAHV), low arousal high valence (LAHV), low arousal low valence (LALV) and high arousal low valence (HALV). The phase lag index as a connectivity index was calculated in theta (4-7 Hz), alpha (8-13 Hz), beta (14-30 Hz) and gamma (31-45 Hz) bands. Hemispheric networks were constructed for each trial, and graph theory was applied to quantify the hemispheric networks' topological properties. Statistical analyses showed significant topological differences in the gamma band. The left hemispheric network showed significantly higher clustering coefficient (Cp), global efficiency (Eg) and local efficiency (Eloc) and lower characteristic path length (Lp) under HAHV emotion. The right hemispheric network showed significantly higher Cp and Eloc and lower Lp under HALV emotion. The results showed that the left hemisphere was dominant for HAHV emotion, while the right hemisphere was dominant for HALV emotion. The research revealed the relationship between emotion and hemispheric asymmetry from the perspective of brain networks.

8.
J Phys Chem Lett ; : 517-524, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33375789

RESUMO

The coordination environments of iron (Fe) in Fe-N-C catalysts determine their intrinsic activities toward oxygen reduction reactions (ORR). The precise atomic-level regulation of the local coordination environments is thus of critical importance yet quite challenging to achieve. Here, atomically dispersed Fe-N-C catalyst with O-Fe-N2C2 moieties is thoroughly studied for ORR catalysis. Advanced synchrotron X-ray characterizations, along with theoretical modeling, explicitly unraveled the penta-coordinated nature of the Fe center in the catalytic domain and the energetically optimized ORR pathways on the well-tailored O-Fe-N2C2 moieties. The combined structure identification from both experiments and theory provides an opportunity to understand the role of the coordination environments in directing the catalytic activity of single-atom or single-site catalysts; not only the center metal atom but also the whole coordinating atoms participate in the catalytic cycle.

9.
Int J Immunogenet ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33369094

RESUMO

BACKGROUND: The published evidences on the correlations of toll-like receptor 4 (TLR4) and TLR9 gene polymorphisms and ankylosing spondylitis (AS) were conflicting. The purpose of this study was to investigate whether TLR4 and TLR9 gene polymorphisms conferred susceptibility to AS through a meta-analysis approach. METHODS: Databases of PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang were retrieved for relevant publications up to 20 June 2020. Study quality was assessed based on Newcastle-Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to judge the associations. RESULTS: Totally, 13 articles with 3,055 AS cases and 4,238 controls were incorporated into this meta-analysis, and four most widely reported polymorphisms (TLR4-rs4986790, TLR4-rs4986791, TLR9-rs55704465 and TLR9-rs187084) were analysed. All included studies were in high quality. The pooled data did not support any significant association between the four studied polymorphisms and AS susceptibility. CONCLUSIONS: The present meta-analysis suggests there is no significant association between TLR4-rs4986790, TLR4-rs4986791, TLR9-rs55704465 and TLR9-rs187084 polymorphisms and AS.

10.
Iran J Immunol ; 17(4): 292-302, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382386

RESUMO

BACKGROUND: In a previous study, the unrecognized role of gMYL6 in the up-regulation of human NK cells development and cytotoxicity was reported. OBJECTIVE: To further elucidate the mechanism of action of small recombinant fragments of gMYL6 enhancing the NK cells activity. METHODS: Mononuclear cells were isolated from umbilical cord blood (UCB) by density-gradient centrifugation and NK cells were propagated and cultured. The small peptides from the gMYL6, with the ability to enhance the cytotoxicity of NK cells were screened by CCK-8 method and one of the most powerful peptides was identified for the next study. Flow cytometry was used to assess the proliferation and apoptosis of K562 cells, as well as the cell cycle arrest. The apoptosis of target cells was observed by AO/EB fluorescence staining, and the degree of apoptosis was assessed by flow cytometry. Protein imprinting method was also used to explore the pathway of small peptides to enhance the NK cells' activity. On the other hand, Real-time Quantitative PCR Detecting System was used to verify the mechanism of K562 cells suppression. RESULTS: Small D peptide significantly increased NK cells cytotoxicity and induced both cell cycle arrest at G2/M and apoptosis of K562 cells. CONCLUSION: Small D peptide could be a novel promising peptide for cancer immunotherapy since it was shown to promote the cytotoxicity of cord blood-derived NK cells.

11.
Med Sci Monit ; 26: e926142, 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33361735

RESUMO

BACKGROUND This study aimed to investigate the safety and clinical efficacy of 3 different surgical methods for treating spinal tuberculosis (ST) in children. MATERIAL AND METHODS We reviewed the cases of 62 children with ST who were treated in our hospital from January 2010 to December 2014. In this study, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Frankel classification of neurological function, pain visual analog scale (VAS) score, and kyphosis Cobb (k-Cobb) angle were dynamically monitored to evaluate the efficacy of different surgical methods. Complications in the patients were evaluated at 3 time points: before surgery (T1), after surgery (T2), and during final follow-up (T3). The average follow-up was 27.4 months. Twenty-two patients underwent simple anterior debridement alone or combined with internal fixation (Method A), 13 patients underwent posterior debridement alone (Method B), and 27 patients received anteroposterior debridement and bone graft fusion together with internal fixation (Method C). RESULTS In all 3 groups after surgery, ESR, CRP levels, VAS scores, and k-Cobb angles significantly decreased. However, compared with patients who received Methods B and C, patients who received Method A had a significant rebound in k-Cobb angle and a higher incidence of complications at the T3 time point. The overall reoperation rate during follow-up was 37.10%. Fourteen patients (22.58%) had kyphosis, 2 patients (3.23%) had tuberculosis recurrence combined with kyphosis, and other complications were reported in 5 patients (8.06%). CONCLUSIONS Considering the incidence of complications and level of postoperative biochemical indicators, we concluded that caution should be exercised in using an anterior approach to treat pediatric ST.

12.
R Soc Open Sci ; 7(10): 201078, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33204466

RESUMO

We have synthesized a new series of layered oxyselenides Bi2LnO4Cu2Se2 (Ln=Nd, Sm, Eu, Dy, Er, Yb). Their crystal structures and physical properties were studied through X-ray diffraction, electric transport measurements, bulk magnetization and first-principle calculation. All these compounds have a tetragonal structure with space group I4/mmm. They exhibit hole-type metallic behaviours which is also verified by the DFT calculation. The new Bi2LnO4-type block in these compounds may give people some enlightenment in synthesizing new iron-based superconductors or other layered compounds.

13.
Front Microbiol ; 11: 592592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250880

RESUMO

In this study, compound microbial inoculants, including three Bacillus strains and one Yeast strain, were inoculated into swine manure composting to explore the effects on antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), microbial community structure, and pathogenic bacteria. The results indicated that the abundances of the detected ARGs ranged from 3.6 × 103 to 1.13 × 108 copies/g. The ARGs with the highest abundance was sul2, and the lowest was blaCTX. Composting removes most of the ARGs and MGEs by 22.8-99.7%. These ARGs were significantly reduced during the thermophilic phase of compost. The removal rate of ARGs at the different layers of compost pile was different as follows: middle layer > upper layer > lower layer. But some ARGs proliferated significantly in the maturation phase of compost, especially the sulfonamide resistance genes. Compound microbial inoculants increased the temperature of compost, accelerated water loss, nitrogen fixation, and increased the removal rate of ß-lactamase resistance genes, the transposon gene tn916 and part of tetracycline resistance genes by 3.7-23.8% in compost. Compound microbial inoculants changed the community structure and increased the Bacillus abundance in the thermophilic phase of compost. And it was helpful for removing pathogens during composting. The addition of compound microbial inoculants causes the decrease of Firmicutes and the increase of Bacteroidetes, which may be related to the removal and proliferation of ARGs.

14.
Clin Neurol Neurosurg ; : 106325, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33160714

RESUMO

OBJECTIVE: Dozens of reports on the associations of vitamin D receptor (VDR) gene polymorphisms and susceptibility to spinal degenerative disease (SDD) were conducted with inconsistent findings. This study aimed to elucidate the associations through a meta-analysis approach. METHODS: Databases of PubMed, EMBASE, Web of Science, CNKI, and Wanfang were searched until July 10, 2020. Study quality was evaluated by using Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the associations under allelic model (1 vs. 2), homozygous model (11 vs. 22), heterozygous model (12 vs. 22), dominant model (11 + 12 vs. 22), and recessive model (11 vs. 12 + 22). RESULTS: A total of 5021 cases and 5746 controls from 35 studies were eligible to this meta-analysis. According to NOS, the included studies were in excellent quality. In the overall population, the pooled data indicated that ApaI was associated with a reduced SDD susceptibility (AA vs. Aa + aa, OR = 0.83, 95%CI 0.71 - 0.96, P = 0.010). But the association was not observed in FokI, TaqI, and BsmI polymorphisms. Subgroup analysis suggested that TaqI polymorphism was correlated to an elevated SDD risk in Asians (TT + Tt vs. tt, OR = 2.55, 95%CI 1.90 - 3.44, P < 0.001). CONCLUSION: The present study indicates that ApaI polymorphism may contribute to a reduced risk to SDD in the overall population, and TaqI polymorphism confers an elevated susceptibility to SDD in Asians. While, BsmI and FokI polymorphisms appear to have no significant association with SDD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33184920

RESUMO

A photochemical C-N coupling of aryl halides with nitroarenes is demonstrated for the first time. Catalyzed by a Ni(II) complex in the absence of any external photosensitizer, readily available nitroarenes undergo coupling with a variety of aryl halides, providing a step-economic extension to the widely used Buchwald-Hartwig C-N coupling reaction. The method tolerates coupling partners with steric-congestion and functional groups sensitive to bases and nucleophiles. Mechanistic studies suggest that the reaction proceeds via the addition of an aryl radical, generated from a Ni (I)/Ni (III) cycle, to a nitrosoarene intermediate.

16.
Dis Markers ; 2020: 8833972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204364

RESUMO

Lymph node (LN) metastasis is a lethal independent risk factor for patients with bladder cancer (BLCA). Accurate evaluation of LN metastasis is of vital importance for disease staging, treatment selection, and prognosis prediction. Several histopathologic parameters are available to predict LN metastasis postoperatively. To date, medical imaging techniques have made a great contribution to preoperatively diagnosis of LN metastasis, but it also exhibits substantial false positives. Therefore, a reliable and robust method to preoperatively predict LN metastasis is urgently needed. Here, we selected 19 candidate genes related to epithelial-mesenchymal transition (EMT) across the LN metastasis samples, which was previously reported to be responsible for the subtype transition and correlation with malignancy and prognosis of BLCA, to establish an EMT-LN signature through LASSO logistic regression analysis. The EMT-LN signature could significantly predict LN metastasis with high accuracy in the TCGA-BLCA cohort, as well as several independent cohorts. As integrating with C3orf70 mutation, we developed an individualized prediction nomogram based on the EMT-LN signature. The nomogram exhibited good discrimination on LN metastasis status, with AUC of 71.7% and 75.9% in training and testing datasets of the TCGA-BLCA cohort. Moreover, the EMT-LN nomogram displayed good calibration with p > 0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the EMT-LN nomogram was of high potential for clinical utility. In summary, we established an EMT-LN nomogram integrating an EMT-LN signature and C3orf70 mutation status, which acted as an easy-to-use tool to facilitate preoperative prediction of LN metastasis in BLCA individuals.

17.
Adv Sci (Weinh) ; 7(19): 2001431, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33042754

RESUMO

Black phosphorus (BP), an emerging 2D material semiconductor material, exhibits unique properties and promising application prospects for photo/electrocatalysis. However, the applications of BP in photo/electrocatalysis are hampered by the instability as well as low catalysis efficiency. Recently, tremendous efforts have been dedicated toward modulating its intrinsic structure, electronic property, and charge separation for enhanced photo/electrocatalytic performance through structure engineering. Simultaneously, the search for new substitute materials that are BP-analogous is ongoing. Herein, the latest theoretical and experimental progress made in the structural/surface engineering strategies and advanced applications of BP and BP-analog materials in relation to photo/electrocatalysis are extensively explored, and a presentation of the future opportunities and challenges of the materials is included at the end.

18.
Research (Wash D C) ; 2020: 7593023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33094289

RESUMO

Identification of an active center of catalysts under realistic working conditions of oxygen reduction reaction (ORR) still remains a great challenge and unclear. Herein, we synthesize the Cu single atom embedded on nitrogen-doped graphene-like matrix electrocatalyst (abbreviated as SA-Cu/NG). The results show that SA-Cu/NG possesses a higher ORR capability than 20% Pt/C at alkaline solution while the inferior activity to 20% Pt/C at acidic medium. Based on the experiment and simulation calculation, we identify the atomic structure of Cu-N2C2 in SA-Cu/NG and for the first time unravels that the oxygen-reconstituted Cu-N2C2-O structure is really the active species of alkaline ORR, while the oxygen reconstitution does not happen at acidic medium. The finding of oxygen-reconstituted active species of SA-Cu/NG at alkaline media successfully unveils the bottleneck puzzle of why the performance of ORR catalysts at alkaline solution is better than that at acidic media, which provides new physical insight into the development of new ORR catalysts.

19.
Theranostics ; 10(24): 11080-11091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042271

RESUMO

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy. However, current MSI identification methods are not available for all patients. We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation. Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC). We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction. The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation. Results: The EPLA model achieved an area-under-the-curve (AUC) of 0.8848 (95% CI: 0.8185-0.9512) in the TCGA-COAD test set and an AUC of 0.8504 (95% CI: 0.7591-0.9323) in the external validation set Asian-CRC after transfer learning. Notably, EPLA captured the relationship between pathological phenotype of poor differentiation and MSI (P < 0.001). Furthermore, the five pathological imaging signatures identified from the EPLA model were associated with mutation burden and DNA damage repair related genotype in the genomic profiles, and antitumor immunity activated pathway in the transcriptomic profiles. Conclusions: Our pathomics-based deep learning model can effectively predict MSI from histopathology images and is transferable to a new patient cohort. The interpretability of our model by association with pathological, genomic and transcriptomic phenotypes lays the foundation for prospective clinical trials of the application of this artificial intelligence (AI) platform in ICB therapy.

20.
ACS Chem Neurosci ; 11(21): 3549-3556, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33079539

RESUMO

Inflammation is the primary pathological feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Proinflammatory molecules (e.g., S100A9) play important roles during the progression of the diseases by regulating behavior and fate of multiple cell types in the nervous system. Our earlier studies reveal that S100A9 is toxic to neurons, and its interaction with Aß peptides leads to the formation of large nontoxic amyloidogenic aggregates, suggesting a protective role of coaggregation with Aß amyloids. We herein demonstrate that S100A9 interacts with neural stem cells (NSCs) and causes NSC differentiation. In the brain of transgenic AD mouse models, we found large quantities of proinflammatory S100A9, which colocalizes with the differentiated NSCs. NSC sphere formation, which is a representative character of NSC stemness, is also substantially inhibited by S100A9. These results suggest that S100A9 is a representative marker for the inflammatory conditions in AD, and it promotes NSC differentiation. Intriguingly, in contrast to the death of both stem and differentiated NSCs caused by high S100A9 doses, S100A9 at a moderate concentration is toxic only to the early differentiated NSCs but not the stem cells. We therefore postulate that, at the early stage of AD, the expression of S100A9 leads to NSC differentiation, which remedies the neuron damage. The application of drugs, which help maintain NSC stemness (e.g., the platelet-derived growth factor, PDGF), may help overcome the acute inflammatory conditions and improve the efficacy of NSC transplantation therapy.

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