Pepticinnamins N, O, and P, Nonribosomal Peptides from the Soil-Derived Streptomyces mirabilis P8-A2.

Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O, and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions. These new compounds did not show a growth inhibitory effect against the LNCaP and C4-2B prostate cancer lines, respectively.

Genome-Driven Discovery of Hygrocins in Streptomyces rapamycinicus.

Ansamycins, represented by the antituberculosis drug rifamycin, are an important family of natural products. To obtain new ansamycins, Streptomyces rapamycinicus IMET 43975 harboring an ansamycin biosynthetic gene cluster was fermented in a 50 L scale, and subsequent purification work led to the isolation of five known and four new analogues, where hygrocin W (2) belongs to benzoquinonoid ansamycins, and the other three hygrocins, hygrocins X-Z (6-8), are new seco-hygrocins. The structures of ansamycins (1-8) were determined by the analysis of spectroscopic (1D/2D NMR and ECD) and MS spectrometric data. The Baeyer-Villiger enzyme which catalyzed the ester formation in the ansa-ring was confirmed through in vivo CRISPR base editing. The discovery of these compounds further enriches the structural diversity of ansamycins.

A fine-scale Arabidopsis chromatin landscape reveals chromatin conformation-associated transcriptional dynamics.

Plants, as sessile organisms, deploy transcriptional dynamics for adapting to extreme growth conditions such as cold stress. Emerging evidence suggests that chromatin architecture contributes to transcriptional regulation. However, the relationship between chromatin architectural dynamics and transcriptional reprogramming in response to cold stress remains unclear. Here, we apply a chemical-crosslinking assisted proximity capture (CAP-C) method to elucidate the fine-scale chromatin landscape, revealing chromatin interactions within gene bodies closely associated with RNA polymerase II (Pol II) densities across initiation, pausing, and termination sites. We observe dynamic changes in chromatin interactions alongside Pol II activity alterations during cold stress, suggesting local chromatin dynamics may regulate Pol II activity. Notably, cold stress does not affect large-scale chromatin conformations. We further identify a comprehensive promoter-promoter interaction (PPI) network across the genome, potentially facilitating co-regulation of gene expression in response to cold stress. Our study deepens the understanding of chromatin conformation-associated gene regulation in plant response to cold.

Synthesis of ZSM-5 Zeolite Nanosheets with Tunable Silanol Nest Contents across an Ultra-wide pH Range and Their Catalytic Validation.

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH < 10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH ≥ 10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.

A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy.

PURPOSE: DNA methylation alterations are widespread in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. While the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. EXPERIMENTAL DESIGN: We performed global DNA methylation profiling in a case-control study nested within Singapore Chinese Health Study to evaluate if DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years prior to diagnosis of AML or MDS, together with age-matched still healthy individuals as controls. RESULTS: Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow up period. Alterations in methylation in the differentially methylation regions (DMRs) were associated with increased odds of developing AML/MDS. CONCLUSIONS: The epigenetic changes may be acquired independently and prior to somatic mutations that relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre- AML/MDS screening.

Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

Estuarine environmental flow assessment based on the flow-ecological health index relation model: a case study in Yangtze River Estuary, China.

Environmental flow (e-flow) is the water demand of one given ecosystem, which can become the flow regulation target for protection and restoration of river or estuarine ecosystems. In this study, an e-flow assessment based on the flow-ecological health index (EHI) relation model was conducted to improve ecosystem health of the Yangtze River Estuary (YRE). Monitoring data of hydrology, biology, and water environment in the last decades were used for the model establishment. For the description of the YRE ecosystem, an EHI system was developed by cumulative frequency distribution curves and adaption of national standards. After preprocessing original flow values into proportional flow values, the generalized additive model and Monte Carlo random sampling were used for the establishment of the flow-EHI relation model. From the model calculation, the e-flow assessment results were that, in proportional flow values, the suitable flow range was 1.05-1.35, and the optimum flow range was 1.15-1.25 (flows in Yangtze River Datong Station). For flow regulation in two crucial periods, flows of 42,630-65,545 m3/s or over 14,675 m3/s are needed for the suitable flow of YRE in summer (June-August) or January, respectively. An adaptive management framework of ecological health-based estuarine e-flow assessment for YRE was contrived due to the limitation of current established model when facing the extreme drought in summer, 2022. The methodology and framework in this study are expected to provide valuable management and data support for the sustainable development of estuarine ecosystems and to bring inspiration for further studies at even continental or global levels.

Polymer-Based Drug Delivery Systems for Cancer Therapeutics.

Chemotherapy together with surgery and/or radiotherapy are the most common therapeutic methods for treating cancer. However, the off-target effects of chemotherapy are known to produce side effects and dose-limiting toxicities. Novel delivery platforms based on natural and synthetic polymers with enhanced pharmacokinetic and therapeutic potential for the treatment of cancer have grown tremendously over the past 10 years. Polymers can facilitate selective targeting, enhance and prolong circulation, improve delivery, and provide the controlled release of cargos through various mechanisms, including physical adsorption, chemical conjugation, and/or internal loading. Notably, polymers that are biodegradable, biocompatible, and physicochemically stable are considered to be ideal delivery carriers. This biomimetic and bio-inspired system offers a bright future for effective drug delivery with the potential to overcome the obstacles encountered. This review focuses on the barriers that impact the success of chemotherapy drug delivery as well as the recent developments based on natural and synthetic polymers as platforms for improving drug delivery for treating cancer.

PM2.5 induce neurotoxicity via iron overload and redox imbalance mediated-ferroptosis in HT22 cells.

PM2.5 is an important risk factor for the development and progression of cognitive impairment-related diseases. Ferroptosis, a new form of cell death driven by iron overload and lipid peroxidation, is proposed to have significant implications. To verify the possible role of ferroptosis in PM2.5-induced neurotoxicity, we investigated the cytotoxicity, intracellular iron content, iron metabolism-related genes, oxidative stress indices and indicators involving in Nrf2 and ferroptosis signaling pathways. Neurotoxicity biomarkers as well as the ferroptotic cell morphological changes were determined by Western Blot and TEM analysis. Our results revealed that PM2.5 induced cytotoxicity, lipid peroxidation, as indicated by MDA content, and neurotoxicity via Aß deposition in a dose-related manner. Decreased cell viability and excessive iron accumulation in HT-22 cells can be partially blocked by ferroptosis inhibitors. Interestingly, GPX activity, Nrf2, and its regulated ferroptotic-related proteins (i.e. GPX4 and HO-1) were significantly up-regulated by PM2.5. Moreover, gene expression of DMT1, TfR1, IRP2 and FPN1 involved in iron homeostasis and NCOA4-dependent ferritinophagy were activated after PM2.5 exposure. The results demonstrated that PM2.5 triggered ferritinophagy-dependent ferroptotic cell death due to iron overload and redox imbalance. Activation of Nrf2 signaling pathways may confer a protective mechanism for PM2.5-induced oxidative stress and ferroptosis.

Investigation on acoustic emission characteristics of fault stick-slip under different lateral pressures.

To explore the effect of different stress environments on fault-slip rockbursts. Bidirectional shear friction experiments with different lateral pressures were conducted on precracked syenogranites buried at 800 m. The macroscopic statistical parameters (cumulative number of AE events, magnitude and b value) and local characteristic parameters (amplitude and dominant frequency) of acoustic emission during the stick-slip process under different lateral pressures were investigated. In addition, based on fractal theory, the nonlinear characteristics of AE spectrum were analyzed. On this basis, the microscopic mechanism of fault stick-slip was discussed. The results show that the lateral pressure influences the friction strength of the fault and stick-slip motion characteristics. With increasing lateral pressure, the proportion of transgranular shear fractures increases, which leads to an increase of cumulative number of AE events and magnitude. The periodic decrease in the b value is more significant at high lateral pressure. There is a good correlation between a high-magnitude AE event and a stress drop. The AE frequency with phased response characteristics can be used to effectively identify the evolution of fault stick-slip instability at the laboratory scale. A sharp increase in the amplitude of the dominant frequency can be regarded as one of the precursory features of fault stick-slip instability. The AE frequency spectra have multifractal characteristics, that differ among the different stages. The maximum multifractal dimension and spectral width can reflect the difference in energy released during fault stick-slip motion.

Recurrence of hypertriglyceridemia-associated acute pancreatitis: A multicenter, prospective cohort study.

OBJECTIVES: There are scarce prospective data on recurrent hypertriglyceridemia-associated acute pancreatitis (HTG-AP). This study aimed to investigate the incidence, potential prognostic factors, and clinical relevance of recurrent HTG-AP. METHODS: This study is a multicenter, prospective cohort study. Adult patients with the first HTG-AP attack enrolled in the PERFORM registry between November 2020 and December 2021 were involved. All the study patients were followed up for more than two years with a two-round schedule. The Cox proportional-hazards model was applied to analyze the potential factors. Quality of life was evaluated using the EuroQol five-dimensional five-level health scale (EQ-5D-5L). RESULTS: A total of 184 patients from 25 sites were included in the study, and 161 patients completed the two-round follow-up. Among them, the mean follow-up time for the study patients was 31±4 months, and the incidence rate of recurrent HTG-AP attack was 23 % (37/161). All patients with recurrent episodes required readmission to the hospital. The EQ visual analog scale (VAS) score was significantly lower in patients with recurrent episodes compared to those without (76±10 vs. 82±12; P = 0.02) at the latest follow-up. Age <40 years old (hazard ratio [HR], 3.6; 95 % confidence interval [CI], 1.5-8.7; P = 0.004) and a history of diabetes (HR, 2.6; 95 %CI, 1.3-5.1; P = 0.005) were identified as potential predictor factors for recurrence. CONCLUSIONS: Recurrence of HTG-AP is common, especially for younger patients with diabetes. Recurrence necessitated additional hospital readmissions and was associated with compromised quality of life.

Identification of potential core genes in pseudoexfoliation using bioinformatics analysis and retrospective analysis of 84 patients with this disease.

BACKGROUND: Pseudoexfoliation (XFS) is a common cause of glaucoma in nowadays. Because of XFS causing irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Xinjiang Province of China, and identify the hub genes involved in XFS. METHODS: A retrospective chart review was conducted from 2007 to 2019 for patients aged 50 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review. RESULTS: Of the 84 patient charts available for review, 50% of the patients identified as male, with a mean age of 67 years. The top ten genes evaluated by connectivity degree in the PPI network were identified. The results showed that Tyrobp was the most outstanding gene, followed by Ptprc, Fcgr3, Itgb2, Emr1, Cd68, Syk, Fcerlg, Hck, and Lyz2. All of these hub genes were downregulated in XFS. CONCLUSION: Our findings show a considerably biomarkers of XFS for diagnosis and treatment.

Cediranib enhances the transcription of MHC-I by upregulating IRF-1.

Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8+ T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy.

Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2.

Azoxy compounds are a distinctive group of bioactive secondary metabolites characterized by a unique RN═N+(O-)R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins are cytotoxic azoxy metabolites produced by Streptomyces mirabilis P8-A2. Here, we cloned and confirmed the putative azd biosynthetic gene cluster through CATCH cloning followed by expression and production of azodyrecins in two heterologous hosts, S. albidoflavus J1074 and S. coelicolor M1146, respectively. We explored the function of 14 enzymes in azodyrecin biosynthesis through gene knockout using CRISPR-Cas9 base editing in the native producer, S. mirabilis P8-A2. The key intermediates were analyzed in the mutants through MS/MS fragmentation studies, revealing azoxy bond formation via the conversion of hydrazine to an azo compound followed by further oxygenation. Enzymes involved in modifications of the precursor could be postulated based on their predicted function and the intermediates identified in the knockout strains. Moreover, the distribution of the azoxy biosynthetic gene clusters across Streptomyces spp. genomes is explored, highlighting the presence of these clusters in over 20% of the Streptomyces spp. genomes and revealing that azoxymycin and valanimycin are scarce, while azodyrecin and KA57A-like clusters are widely distributed across the phylogenetic tree.

Single cell RNA-sequencing data generated from mouse adipose tissue during the development of obesity.

In recent years, the number of obesity has increased rapidly around the world, and it has become a major public health problem endangering global health [1]. Obesity is caused by excessive calorie intake over a long period of time, and high-fat diet (HFD) is one of the important predisposing factors [2], [3], [4]. Adipose tissue (AT) is an important immune and endocrine organ in the body, and plays an important role in the body [5]. Obesity leads to AT dysfunction, AT dilation and cell hypertrophy. Dysfunctional fat cells are the main source of pro-inflammatory cytokines, which aggravate low-grade systemic inflammation and further promote the development of obesity-related diseases [6], [7], [8]. However, whether AT releases pro-inflammatory cytokines in the early stages of obesity development remains unknown. The AT microenvironment is composed of a variety of cells, including fat cells, immune cells, fibroblasts, and endothelial cells. The immune microenvironment (TIME) and its metabolic imbalance can lead to the secretion or regulation of related hormones, which causes inflammation AT [9]. TIME is very important for maintaining AT homeostasis, which is crucial for the occurrence of obesity [10,11]. This data use single-cell RNA sequencing (sNuc-Seq) to analyze the characteristics of TIME changes in the mouse epididymal adipose tissue during the development of obesity, and the changes of cell types and genes in the tissue.

Evaluating for correlations between metabolites in patients receiving immunotherapy for metastatic or recurrent NSCLC: an exploratory study based on two cohorts.

ICIs have demonstrated stunning clinical efficacy in NSCLC. However, most patients do not achieve long-term survival. Minimally invasive collected samples are attracting significant interest as new fields of biomarker study, and metabolomics is one of these growing fields. We focused on the added value of the metabolomic profile as a means of distinguishing long-term survival from short-term survival in NSCLC patients treated with ICIs.: We prospectively recruited 97 patients with stage IV NSCLC who were treated with anti-PD-1 inhibitor, including patients treated with monoimmunotherapy as second-line treatment (Cohort 1), and patients treated with combination immunotherapy as first-line treatment (Cohort 2). Each cohort was divided into long-term survival and short-term survival groups. All blood samples were collected before beginning immunotherapy. Metabolomic profiling of serum was performed by UHPLC-Q-TOF MS analysis. A total of 41 unique metabolites in Cohort 1 and 47 in Cohort 2 were screened. In Cohort 1 and 2, In cohort 1, the top 3 enriched KEGG pathways, as determined through significant different metabolic pathway analysis, were primary bile acid biosynthesis, african trypanosomiasis, and choline metabolism in cancer. In Cohort 2, the top 3 enriched KEGG pathways were the TCA cycle, PPAR signaling pathway, and primary bile acid biosynthesis. The primary bile acid synthesis pathway had significant differences in the long-term survival and short-term survival groups in both Cohort 1 and Cohort 2.Our study suggests that peripheral blood metabolomic analysis is critical for identifying metabolic biomarkers and metabolic pathways responsible for the NSCLC patients treated with ICIs.

Graph-Based Semi-Supervised Deep Image Clustering With Adaptive Adjacency Matrix.

Image clustering is a research hotspot in machine learning and computer vision. Existing graph-based semi-supervised deep clustering methods suffer from three problems: 1) because clustering uses only high-level features, the detailed information contained in shallow-level features is ignored; 2) most feature extraction networks employ the step odd convolutional kernel, which results in an uneven distribution of receptive field intensity; and 3) because the adjacency matrix is precomputed and fixed, it cannot adapt to changes in the relationship between samples. To solve the above problems, we propose a novel graph-based semi-supervised deep clustering method for image clustering. First, the parity cross-convolutional feature extraction and fusion module is used to extract high-quality image features. Then, the clustering constraint layer is designed to improve the clustering efficiency. And, the output layer is customized to achieve unsupervised regularization training. Finally, the adjacency matrix is inferred by actual network prediction. A graph-based regularization method is adopted for unsupervised training networks. Experimental results show that our method significantly outperforms state-of-the-art methods on USPS, MNIST, street view house numbers (SVHN), and fashion MNIST (FMNIST) datasets in terms of ACC, normalized mutual information (NMI), and ARI.

Microbial metabolism influences microplastic perturbation of dissolved organic matter in agricultural soils.

An estimated 258 million tons of plastic enter the soil annually. Joining persistent types of microplastic (MP), there will be an increasing demand for biodegradable plastics. There are still many unknowns about plastic pollution by either type, and one large gap is the fate and composition of dissolved organic matter (DOM) released from MPs as well as how they interact with soil microbiomes in agricultural systems. In this study, polyethylene MPs, photoaged to different degrees, and virgin polylactic acid MPs were added to agricultural soil at different levels and incubated for 100 days to address this knowledge gap. We find that, upon MP addition, labile components of low aromaticity were degraded and transformed, resulting in increased aromaticity and oxidation degree, reduced molecular diversity, and changed nitrogen and sulfur contents of soil DOM. Terephthalate, acetate, oxalate, and L-lactate in DOM released by polylactic acid MPs and 4-nitrophenol, propanoate, and nitrate in DOM released by polyethylene MPs were the major molecules available to the soil microbiomes. The bacteria involved in the metabolism of DOM released by MPs are mainly concentrated in Proteobacteria, Actinobacteriota, and Bacteroidota, and fungi are mainly in Ascomycota and Basidiomycota. Our study provides an in-depth understanding of the microbial transformation of DOM released by MPs and its effects of DOM evolution in agricultural soils.

Insights into the role of derailed endocytic trafficking pathway in cancer: From the perspective of cancer hallmarks.

The endocytic trafficking pathway is a highly organized cellular program responsible for the regulation of membrane components and uptake of extracellular substances. Molecules internalized into the cell through endocytosis will be sorted for degradation or recycled back to membrane, which is determined by a series of sorting events. Many receptors, enzymes, and transporters on the membrane are strictly regulated by endocytic trafficking process, and thus the endocytic pathway has a profound effect on cellular homeostasis. However, the endocytic trafficking process is typically dysregulated in cancers, which leads to the aberrant retention of receptor tyrosine kinases and immunosuppressive molecules on cell membrane, the loss of adhesion protein, as well as excessive uptake of nutrients. Therefore, hijacking endocytic trafficking pathway is an important approach for tumor cells to obtain advantages of proliferation and invasion, and to evade immune attack. Here, we summarize how dysregulated endocytic trafficking process triggers tumorigenesis and progression from the perspective of several typical cancer hallmarks. The impact of endocytic trafficking pathway to cancer therapy efficacy is also discussed.

PEGylated-liposomal astaxanthin ameliorates Aß neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde.

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.