Microwave-Assisted Pyrolysis-A New Way for the Sustainable Recycling and Upgrading of Plastic and Biomass: A Review.

The efficient utilization of organic solid waste resources can help reducing the consumption of conventional fossil fuels, mitigating environmental pollution, and achieving green sustainable development. Due to its dual nature of being both a resource and a source of pollution, it is crucial to implement suitable recycling technologies throughout the recycling and upgrading processes for plastics and biomass, which are organic solid wastes with complex mixture of components. The conventional pyrolysis and hydropyrolysis were summarized for recycling plastics and biomass into high-value fuels, chemicals, and materials. To enhance reaction efficiency and improve product selectivity, microwave-assisted pyrolysis was introduced to the upgrading of plastics and biomass through efficient energy supply especially with the aid of catalysts and microwave absorbers. This review provides a detail summary of microwave-assisted pyrolysis for plastics and biomass from the technical, applied, and mechanistic perspectives. Based on the recent technological advances, the future directions for the development of microwave-assisted pyrolysis technologies are predicted.

A Multi-Task Network Based on Dual-Neck Structure for Autonomous Driving Perception.

A vision-based autonomous driving perception system necessitates the accomplishment of a suite of tasks, including vehicle detection, drivable area segmentation, and lane line segmentation. In light of the limited computational resources available, multi-task learning has emerged as the preeminent methodology for crafting such systems. In this article, we introduce a highly efficient end-to-end multi-task learning model that showcases promising performance on all fronts. Our approach entails the development of a reliable feature extraction network by introducing a feature extraction module called C2SPD. Moreover, to account for the disparities among various tasks, we propose a dual-neck architecture. Finally, we present an optimized design for the decoders of each task. Our model evinces strong performance on the demanding BDD100K dataset, attaining remarkable accuracy (Acc) in vehicle detection and superior precision in drivable area segmentation (mIoU). In addition, this is the first work that can process these three visual perception tasks simultaneously in real time on an embedded device Atlas 200I A2 and maintain excellent accuracy.

Optoelectronic Torque Measurement System Based on SAPSO-RBF Algorithm.

The torque is a significant indicator reflecting the comprehensive operational characteristics of a power system. Thus, accurate torque measurement plays a pivotal role in ensuring the safety and stability of the system. However, conventional torque measurement systems predominantly rely on strain gauges adhered to the shaft, often leading to reduced accuracy, poor repeatability, and non-traceability due to the influence of strain gauge adhesion. To tackle the challenge, this paper introduces a photoelectric torque measurement system. Quadrants of photoelectric sensors are employed to capture minute deformations induced by torque on the rotational axis, converting them into measurable voltage. Subsequently, the system employs the radial basis function neural network optimized by simulated annealing combined with particle swarm algorithm (SAPSO-RBF) to establish a correlation between measured torque values and standard references, thereby calibrating the measured values. Experimental results affirm the system's capability to accurately determine torque measurements and execute calibration, minimizing measurement errors to 0.92%.

Prognostic value of normal levels of preoperative tumor markers in colorectal cancer.

Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment.

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment's fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.

PURPOSE: The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. METHODS: The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. RESULTS: Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. CONCLUSION: This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

Design and implementation of high sampling rate and multichannel wireless recorder for EEG monitoring and SSVEP response detection.

Introduction: The collection and process of human brain activity signals play an essential role in developing brain-computer interface (BCI) systems. A portable electroencephalogram (EEG) device has become an important tool for monitoring brain activity and diagnosing mental diseases. However, the miniaturization, portability, and scalability of EEG recorder are the current bottleneck in the research and application of BCI. Methods: For scalp EEG and other applications, the current study designs a 32-channel EEG recorder with a sampling rate up to 30 kHz and 16-bit accuracy, which can meet both the demands of scalp and intracranial EEG signal recording. A fully integrated electrophysiology microchip RHS2116 controlled by FPGA is employed to build the EEG recorder, and the design meets the requirements of high sampling rate, high transmission rate and channel extensive. Results: The experimental results show that the developed EEG recorder provides a maximum 30 kHz sampling rate and 58 Mbps wireless transmission rate. The electrophysiological experiments were performed on scalp and intracranial EEG collection. An inflatable helmet with adjustable contact impedance was designed, and the pressurization can improve the SNR by approximately 4 times, the average accuracy of steady-state visual evoked potential (SSVEP) was 93.12%. Animal experiments were also performed on rats, and spike activity was captured successfully. Conclusion: The designed multichannel wireless EEG collection system is simple and comfort, the helmet-EEG recorder can capture the bioelectric signals without noticeable interference, and it has high measurement performance and great potential for practical application in BCI systems.

Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice.

Background: Berberine effectively alleviates non-alcoholic fatty liver disease (NAFLD). Nevertheless, the mechanism is incompletely comprehended. It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of SIRT1 in hepatocytes. We hypothesized that SIRT1 mediated the effect of berberine on NAFLD. Methods: The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet (HFD) and in mouse primary hepatocytes and cell lines exposed to palmitate. The change of fatty acid oxidation (FAO) and the activity of CPT1A were observed in HepG2 cells. Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of SIRT1 and lipid metabolism-related molecules. The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells. Results: Berberine treatment attenuated hepatic steatosis, reduced triglyceride (190.1 ± 11.2 µmol/g liver vs 113.6 ± 7.6 µmol/g liver, P < 0.001) and cholesterol (11.3 ± 2.5 µmol/g liver vs 6.3 ± 0.4 µmol/g liver, P < 0.001) concentration in the liver, and improved lipid and glucose metabolism disorders compared with the HFD group. The expression of SIRT1 was reduced in the liver of NAFLD patients and mouse models. Berberine increased the expression of SIRT1 and promoted the protein level of CPT1A and its activity in HepG2 cells. SIRT1 overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells, whereas SIRT1 knock-down attenuated the effect of berberine. Mechanistically, berberine increased the expression of SIRT1. SIRT1 deacetylated CPT1A at the Lys675 site, which suppressed its ubiquitin-dependent degradation, thereby promoting FAO and alleviating non-alcoholic liver steatosis. Conclusions: Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site, which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.

Quartz tuning fork-based high sensitive photodetector by co-coupling photoelectric and the thermoelastic effect of perovskite.

This paper reports a new strategy for enhancing the photoresponse of a quartz tuning fork (QTF). A deposited light absorbing layer on the surface of QTF could improve the performance only to a certain extent. Herein, a novel strategy is proposed to construct a Schottky junction on the QTF. The Schottky junction presented here consists of a silver-perovskite, which has extremely high light absorption coefficient and dramatically high power conversion efficiency. The co-coupling of the perovskite's photoelectric effect and its related QTF thermoelastic effect leads to a dramatic improvement in the radiation detection performance. Experimental results indicate that the CH3NH3PbI3-QTF obtains two orders of magnitude enhancement in sensitivity and SNR, and the 1σ detection limit was calculated to be 1.9 µW. It was the first time that the QTF resonance detection and perovskite Schottky junction was combined for optical detection. The presented design could be used in photoacoustic spectroscopy and thermoelastic spectroscopy for trace gas sensing.

BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP.

Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that thioredoxin-interacting protein (TXNIP) is a novel BCR-ABL target gene. Suppression of TXNIP was responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provided a novel survival pathway for the transformation of mouse bone marrow cells. Knockout of TXNIP accelerated BCR-ABL transformation, whereas TXNIP overexpression suppressed this transformation. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.

Microcystis spp. and phosphorus in aquatic environments: A comprehensive review on their physiological and ecological interactions.

Cyanobacterial blooms caused by eutrophication have become a major environmental problem in aquatic ecosystems worldwide over the last few decades. Phosphorus is a limiting nutrient that affects the growth of cyanobacteria and plays a role in dynamic changes in algal density and the formation of cyanobacterial blooms. Therefore, identifying the association between phosphorus sources and Microcystis, which is the most representative and harmful cyanobacteria, is essential for building an understanding of the ecological risks of cyanobacterial blooms. However, systematic reviews summarizing the relationships between Microcystis and phosphorus in aquatic environments are rare. Thus, this study provides a comprehensive overview of the physiological and ecological interactions between phosphorus sources and Microcystis in aquatic environments from the following perspectives: (i) the effects of phosphorus source and concentration on Microcystis growth, (ii) the impacts of phosphorus on the environmental behaviors of Microcystis, (iii) mechanisms of phosphorus-related metabolism in Microcystis, and (iv) role of Microcystis in the distribution of phosphorus sources within aquatic environments. In addition, relevant unsolved issues and essential future investigations (e.g., secondary ecological risks) have been highlighted and discussed. This review provides deeper insights into the relationship between phosphorus sources and Microcystis and can serve as a reference for the evaluation, monitoring, and effective control of cyanobacterial blooms.

Tadalafil increases the antitumor activity of 5-FU through inhibiting PRMT5-mediated glycolysis and cell proliferation in colorectal cancer.

BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) is upregulated in multiple tumors and plays a pivotal role in cancer cell proliferation. However, the role of PRMT5 in colorectal cancer remains poorly understood. METHODS: We detected the expression level of PRMT5 and glycolytic enzymes using online databases and colorectal cancer cell lines by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. And MTT and colony formation assays were conducted to investigate cell proliferation. Then, we evaluated ECAR and OCR levels using a biological energy analyzer to investigate the energy status of colorectal cancer, and the transcriptional regulation was detected by dual luciferase reporter assay and ChIP assay. Finally, the efficacy of combined treatment of tadalafil and 5-FU was verified. RESULTS: PRMT5 was highly expressed in colorectal cancer tissues compared with their normal counterparts and correlated with poor prognosis in CRC patients. Then, we demonstrated that PRMT5 knockdown or loss of function attenuated the viability of CRC cells, while overexpression of PRMT5 promoted cell proliferation. Mechanistically, PRMT5 enhanced glycolysis through transcriptionally activating LDHA expression. In addition, the PRMT5 inhibitor, tadalafil, rendered CRC cells sensitive to antitumor agent 5-FU in vitro and in vivo. CONCLUSIONS: Our data indicates that PRMT5 promoted colorectal cancer proliferation partially through activating glycolysis and may be a potential target for colorectal cancer therapy.

Analysis of Prognostic Factors of Rectal Cancer and Construction of a Prognostic Prediction Model Based on Bayesian Network.

Background: The existing prognostic models of rectal cancer after radical resection ignored the relationships among prognostic factors and their mutual effects on prognosis. Thus, a new modeling method is required to remedy this defect. The present study aimed to construct a new prognostic prediction model based on the Bayesian network (BN), a machine learning tool for data mining, clinical decision-making, and prognostic prediction. Methods: From January 2015 to December 2017, the clinical data of 705 patients with rectal cancer who underwent radical resection were analyzed. The entire cohort was divided into training and testing datasets. A new prognostic prediction model based on BN was constructed and compared with a nomogram. Results: A univariate analysis showed that age, Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), Carbohydrate antigen 125 (CA125), preoperative chemotherapy, macropathology type, tumor size, differentiation status, T stage, N stage, vascular invasion, KRAS mutation, and postoperative chemotherapy were associated with overall survival (OS) of the training dataset. Based on the above-mentioned variables, a 3-year OS prognostic prediction BN model of the training dataset was constructed using the Tree Augmented Naïve Bayes method. In addition, age, CEA, CA19-9, CA125, differentiation status, T stage, N stage, KRAS mutation, and postoperative chemotherapy were identified as independent prognostic factors of the training dataset through multivariate Cox regression and were used to construct a nomogram. Then, based on the testing dataset, the two models were evaluated using the receiver operating characteristic (ROC) curve. The results showed that the area under the curve (AUC) of ROC of the BN model and nomogram was 80.11 and 74.23%, respectively. Conclusion: The present study established a BN model for prognostic prediction of rectal cancer for the first time, which was demonstrated to be more accurate than a nomogram.

Erratum: NDRG4 sensitizes CRC cells to 5-FU by upregulating DDIT3 expression.

[This corrects the article DOI: 10.3892/ol.2021.13043.].

[Lipopolysaccharide induces inflammation and up-regulates the expression of methyltransferase-like 3 (METTL3) and METTL14 in human and mouse intestinal epithelial cells].

Objective To investigate the changes of N6-methyladenosine (m6A) modification in the inflammatory status of HIEC-6 human intestinal epithelial cells and MODE-K mouse intestinal epithelial cells. Methods HIEC-6 cells and MODE-K cells were induced by different concentrations of lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor alpha (TNF-α) for 10 hours or the same concentration of LPS, IL-1ß, IL-6 and TNF-α for 0, 3, 6, 12, 24 hours, respectively. The mRNA expression levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were detected by real-time quantitative PCR. The mRNA and protein expression levels of m6A modification-related molecules methyltransferase-like 3 (METTL3), METTL14, METTL16, Wilm's tumor 1-associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), fat-mass and obesity-associated protein (FTO), YTH domain-containing 1 (YTHDC1), YTHDC2 were detected through real-time quantitative PCR and Western blot, respectively. Results The mRNA expression levels of IL-1ß, IL-6 and TNF-α were increased and the mRNA and protein expression levels of METTL3 and METTL14 were simultaneously up-regulated in time-dependent and concentration-dependent LPS-induced model in HIEC-6 cells and MODE-K cells. Conclusion LPS can induce inflammation and up-regulate the expression of METTL3 and METTL14 in intestinal epithelial cells.

Construction of a gut microbiota-gene-pathway network to reveal the molecular mechanisms underlying right- and left-sided colorectal cancer.

Aiming to reveal the molecular mechanisms involved in right- and left-sided colorectal cancer (CRC) development, CRC gene expression data and a microorganism atlas were downloaded from The Cancer Genome Atlas and The Cancer Microbiome Atlas, respectively. The R package was used to screen differentially expressed genes (DEGs) between right- and left-sided CRC samples and identify those related to prognosis, a correlation analysis was performed between DEGs and prognosis-related microbiota, and an interaction network was created using Cytoscape. Finally, a taxon set enrichment analysis of the microbiota was performed and a gene-genus-pathway network was constructed after GO and KEGG analyses. In total, nine out of 1557 identified DEGs had a significant correlation with prognosis, whereas three out of 211 bacterial genera (Fusobacterium, Bacteroides and Parabacteroides) showed a significant correlation with prognosis. DEGs were mainly enriched in the PPAR pathway and vitamin metabolic and transport processes. According to a taxon set enrichment analysis, the microbes in the integrated network were significantly abundant in 28 host-intrinsic, two host-extrinsic and one environment taxon sets. This study provides new insights for understanding the molecular mechanisms of left- and right-CRC.

NDRG4 sensitizes CRC cells to 5-FU by upregulating DDIT3 expression.

The incidence of colorectal cancer (CRC) has remained high in recent years, and 5-fluorouracil (5-FU) is a vital chemotherapeutic agent for its treatment. Our previous study reported that N-myc downstream-regulated gene 4 (NDRG4) plays a tumor-suppressive role in CRC, but the mechanisms associated with NDRG4 and 5-FU chemosensitivity remain unclear. The results of the present study demonstrate that NDRG4 sensitized CRC cells to 5-FU by upregulating DNA damage inducible transcript 3 (DDIT3). NDRG4 inhibited the proliferation of CRC cells and the activation of PI3K/AKT and ERK signaling. Furthermore, NDRG4 promoted CRC cell apoptosis induced by 5-FU. Mechanistic analyses revealed that NDRG4 upregulated DDIT3 expression, and that the proapoptotic effect of NDRG4 under 5-FU treatment conditions was dependent on DDIT3. These findings support the biological value of the association between NDRG4, DDIT3 and 5-FU chemosensitivity in CRC, and may advance the clinical treatment of CRC in the future.

Tissue metabolic profiling reveals major metabolic alteration in colorectal cancer.

Metabolic reprogramming is a hallmark of cancer, which is still far from being fully understood in colorectal cancer. In order to characterize the metabolic changes in colorectal cancer, we performed metabolomics analysis of paired colon tissues from colorectal cancer patients by using a liquid chromatography-mass spectrometry (LC-MS)-based method. Bioinformation analysis was used to define important metabolites and metabolic pathways, as well as the prognosis significance and expression levels of the key molecules. The results indicated that the metabolite phenotype in cancerous colon tissues was obviously different from their normal counterpart, and we identified a series of important metabolic changes in colorectal cancer, including decreased trends of glucose, citrate, serotonin, 5-hydroxytryptophol and 5-hydroxyindoleacetate, as well as increased trends of glutamate, glutathione, creatine, proline, lactate, fructose 1,6-bisphosphate, succinate, tryptophan, kynurenine and long chain acyl-carnitines. These metabolites are mainly implicated in energy metabolism, amino acid metabolism, glutathione metabolism and fatty acid metabolism. In addition, we found that the expression levels of several key molecules in these pathways were closely correlated with the prognosis of colorectal cancer patients. This study characterizes the metabolic profile in colorectal cancer tissues and provides more insightful understanding of the metabolic reprogramming of colorectal cancer.

The differentiation of colorectal cancer is closely relevant to m6A modification.

The occurrence and development of tumors cannot be separated from the influence of differentiation at different stages and levels. Our study found that E-cadherin was significantly increased in cell model induced by sodium butyrate and cell density, while METTL3, METTL16 and WTAP were decreased during the differentiation of cells. In the clinicopathological tissues, E-cadherin was low expressed in poorly differentiated tumor tissues and above three regulators were highly expressed in poorly differentiated tissues. At the levels of clinicopathological differentiation, tissue differentiation and cell differentiation, the result indicated that the poor prognosis of colorectal cancer (CRC) may be closely related to high expression of total m6A level and high expression of METTL3, METTL16 and WTAP.

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment.

Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3ß (GSK-3ß) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1ß, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3ß pathway and finally leading to cognitive impairment.