Lycium barbarum polysaccharide remodels colon inflammatory microenvironment and improves gut health.

Aim: Disturbed intestinal microbiota has been implicated in the inflammatory microenvironment of the colon, which usually results in ulcerative colitis (UC). Given the limitations of these drugs, it is important to explore alternative means of protecting the gut health from UC. This study aimed to investigate the potential of polysaccharides as beneficial nutrients in the regulation of the gut microbiota, which determines the inflammatory microenvironment of the colon. Materials and methods: Mice were treated with dextran sulfate sodium (DSS) to evaluate the effects and mechanisms of Lycium barbarum polysaccharide (LBP) in remodeling the inflammatory microenvironment and improving gut health. Body weight and disease activity indices were monitored daily. Hematoxylin and eosin staining was used to analyze colon dynamics. The levels of inflammatory indicators and expression of MUC-2, claudin-1, ZO-1, and G-protein-coupled receptor 5 (TGR5) were determined using assay kits and immunohistochemistry, respectively. 16S rRNA high-throughput sequencing of the intestinal microbiota and liquid chromatography-tandem mass spectrometry for related bile acids were used. Results: LBP significantly improved the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression. The bacterial genus Dubosiella was dominant in healthy mice, but significantly decreased in mice treated with DSS. LBP rehabilitated Dubosiella in the sick guts of DSS mice to a level close to that of healthy mice. The levels of other beneficial bacterial genera Akkermansia and Bifidobacterium were also increased, whereas those of the harmful bacterial genera Turicibacter, Clostridium_sensu_stricto_1, Escherichia-Shigella, and Faecalibaculum decreased. The activity of beneficial bacteria promoted the bile acids lithocholic and deoxycholic acids in mice with UC, which improved the gut barrier function through the upregulation of TGR5. Conclusion: The inflammatory microenvironment in the gut is determined by the balance of the gut microbiota. LBP showed great potential as a beneficial nutrient for rehabilitating Dubosiella which is dominant in the gut of healthy mice. Nutrient-related LBP may play an important role in gut health management.

Self-assembled co-delivery nanoplatform for increasing the broad-spectrum susceptibility of fall armyworm toward insecticides.

INTRODUCTION: Unscientific application of insecticides has led to severe resistance of pests to almost all classes of insecticides. Enhanced detoxification is the most common mechanism for this kind of resistance. OBJECT: Fall armyworm (FAW) has developed insecticide resistance, which is often linked to the overexpression of detoxification genes. Herein, a multicomponent nano-pesticide is designed to increase its broad-spectrum susceptibility toward insecticides. METHOD: Regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in detoxification was confirmed using transcriptome sequencing, quantitative real-time PCR and enzyme activity measurement. A star polycation (SPc) was adopted to construct the pesticide/SPc/complex, whose self-assembly mechanism and characterization were examined using isothermal titration calorimetry, dynamic light scattering and transmission electron microscope. The delivery efficiency of SPc-loaded dsRNA was examined in vitro and in vivo using fluorescent tracer technique. A multicomponent nano-pesticide was created through the integration of bacterial expression system and nano-delivery system, and its bioactivity was tested in laboratory and field. RESULTS: We confirmed the crucial role of Nrf2 in regulating the detoxification in FAW, and silencing Nrf2 could decrease detoxification gene expression and increase insecticide susceptibility. We then applied the SPc to self-assemble a nanoplatform for delivering Nrf2 double-stranded RNA (dsRNA) and pesticide simultaneously. Nano-sized pesticide/SPc/dsRNA complex exhibited high delivery efficiency in vitro and in vivo. Excitingly, the insecticidal activities of pesticide/SPc/dsNrf2 complexes were remarkably improved with the normalized synergistic ratios of 5.43-6.25 for chlorantraniliprole, 4.45-15.00 for emamectin benzoate, and 6.75-15.00 for spinetoram. Finally, we developed a multicomponent nano-pesticide (pesticide/SPc/dsNrf2 complex) using a bacterial expression system and nano-delivery system. This approach exhibited excellent leaf protection and pest control efficacy. CONCLUSION: The integration between the pesticide nanometerization and insecticide susceptibility improvement offers a promising strategy to increase insecticidal activity. Our study provides a revolutionary and universal strategy to increase insecticidal activity and decease application doses.

The crosstalk between autophagy and myeloid-derived suppressor cell responses in cancer

The development of cancers is aided by the accumulation of myeloid-derived suppressor cells (MDSCs) within tumors, which are highly effective at suppressing anti-tumor immune responses. Direct cell-to-cell interaction and the production of immunosuppressive mediators have both been proposed as pathways for MDSC-mediated suppression of anti-tumor immune responses. The majority of current cancer treatments focus on altering the development and activity of MDSCs so that they have more of an immunogenic character. Autophagy is a catabolic system that contributes to the breakdown of damaged intracellular material and the recycling of metabolites. However, depending on the stage of tumor growth, autophagy can play both a prophylactic and a therapeutic function in carcinogenesis. However, several indirect lines of research have indicated that autophagy is a significant regulator of MDSC activity. The purpose of this work was to outline the interactions between MDSC and autophagy in cancer (AU)

Hybrid-integrated wideband tunable optoelectronic oscillator.

As a photonic-based microwave signal generation method, the optoelectronic oscillator (OEO) has the potential of meeting the increasing demand of practical applications for high frequency, broadband tunability and ultra-low phase noise. However, conventional OEO systems implemented with discrete optoelectronic devices have a bulky size and low reliability, which extremely limits their practical applications. In this paper, a hybrid-integrated wideband tunable OEO with low phase noise is proposed and experimentally demonstrated. The proposed hybrid integrated OEO achieves a high integration level by first integrating a laser chip with a silicon photonic chip, and then connecting the silicon photonic chip with electronic chips through wire-bonding to microstrip lines. A compact fiber ring and an yttrium iron garnet filter are also adopted for high-Q factor and frequency tuning, respectively. The integrated OEO exhibits a low phase noise of -128.04 dBc/Hz @ 10 kHz for an oscillation frequency of 10 GHz. A wideband tuning range from 3 GHz to 18 GHz is also obtained, covering the entire C, X, and Ku bands. Our work demonstrates an effective way to achieve compact high-performance OEO based on hybrid integration, and has great potential in a wide range of applications such as modern radar, wireless communication, and electronic warfare systems.

The crosstalk between autophagy and myeloid-derived suppressor cell responses in cancer.

The development of cancers is aided by the accumulation of myeloid-derived suppressor cells (MDSCs) within tumors, which are highly effective at suppressing anti-tumor immune responses. Direct cell-to-cell interaction and the production of immunosuppressive mediators have both been proposed as pathways for MDSC-mediated suppression of anti-tumor immune responses. The majority of current cancer treatments focus on altering the development and activity of MDSCs so that they have more of an immunogenic character. Autophagy is a catabolic system that contributes to the breakdown of damaged intracellular material and the recycling of metabolites. However, depending on the stage of tumor growth, autophagy can play both a prophylactic and a therapeutic function in carcinogenesis. However, several indirect lines of research have indicated that autophagy is a significant regulator of MDSC activity. The purpose of this work was to outline the interactions between MDSC and autophagy in cancer.

A Fast Prediction Model for Liquid Metal Transfer Modes during the Wire Arc Additive Manufacturing Process.

The liquid metal transfer mode in wire arc additive manufacturing (WAAM), plays an important role in determining the build quality. In this study, a fast prediction model based on the Young-Laplace equation, momentum equation, and energy conservation, is proposed, to identify the metal transfer modes, including droplet, liquid bridge, and wire stubbing, for a given combination of process parameters. To close the proposed model, high-fidelity numerical simulations are applied, to obtain the necessary inputs required by the former. The proposed model's accuracy and effectiveness are validated by using experimental data and high-fidelity simulation results. It is proved that the model can effectively predict the transition from liquid bridge, to droplet and wire stubbing modes. In addition, its errors in dripping frequency and liquid bridge height range from 6% to 18%. Moreover, the process parameter windows about transitions of liquid transfer modes have been established based on the model, considering wire feed speed, travel speed, heat source power, and material parameters. The proposed model is expected to serve as a powerful tool for the guidance of process parameter optimization, to achieve high-quality builds.

Remote Interactive Surgery Platform (RISP): Proof of Concept for an Augmented-Reality-Based Platform for Surgical Telementoring.

The "Remote Interactive Surgery Platform" (RISP) is an augmented reality (AR)-based platform for surgical telementoring. It builds upon recent advances of mixed reality head-mounted displays (MR-HMD) and associated immersive visualization technologies to assist the surgeon during an operation. It enables an interactive, real-time collaboration with a remote consultant by sharing the operating surgeon's field of view through the Microsoft (MS) HoloLens2 (HL2). Development of the RISP started during the Medical Augmented Reality Summer School 2021 and is currently still ongoing. It currently includes features such as three-dimensional annotations, bidirectional voice communication and interactive windows to display radiographs within the sterile field. This manuscript provides an overview of the RISP and preliminary results regarding its annotation accuracy and user experience measured with ten participants.

Long Non-coding RNA KTN1-AS1 Targets miR-505 to Promote Glioblastoma Progression.

Glioblastoma (GBM) is a highly malignant cancer, the prognosis of which is pretty poor. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs, which play important roles in carcinogenesis process of many cancers including GBM. In this study, we want to clarify the expression, biological function, and molecular mechanism of lncRNA KTN1 antisense RNA 1 (KTN1-AS1) in GBM tumor progression. We found that KTN1-AS1 expression was upregulated in GBM tissues and cell lines. KTN1-AS1 played oncogenic roles to facilitate proliferation, migration, and invasion of GBM cells. Then, we revealed that miR-505 was a target of KTN1-AS1, and its expression was decreased in GBM. KTN1-AS1 contributed to GBM progression by mediating miR-505. Finally, we demonstrated that KTN1-AS1 upregulated some target oncogenes of miR-505 including ZEB2, HMGB1, and RUNX2 in GBM cells. All in all, we concluded that the highly expressed KTN1-AS1 in GBM played oncogenic roles to facilitate GBM progression by targeting miR-505.

Deep eutectic solvents-Hydrogels for the topical management of rheumatoid arthritis.

Deep eutectic solvents (DES) have demonstrated their ability to facilitate skin penetrability of rigid nanoparticles (NPs). Here, we reported a feasible and simple transdermal delivery strategy using mesoporous silica nanoparticles impregnated in DES hydrogels for topical management of rheumatoid arthritis (RA). To achieve this goal, nanoceria was immobilized within a silica nanoparticle matrix (MSN) and encapsulated with methotrexate (MTX). The functionalized nanoparticles were first engineered in an Arginine (Arg)-citric acid (CA) DES and then transferred to the carbomer hydrogel matrix. Due to the strong affinity of DES hydrogels to the skin, combined with solvent-driven "Drag" effects, the prepared DES-MSNs hydrogels produced dynamic mobility of MSNs through skin layers, resulting in high skin penetrability. After application to the skin, the hydrogel solvent drove the rigid NPs across the skin barrier in a nonintrusive manner, resulting in sustained penetration and accumulation of MSNs at subcutaneous inflammation sites. Subsequently, the MTX payload exerted a direct therapeutic effect, while nanoceria moderated the inflammatory microenvironment by initiating reactive oxygen species (ROS) scavenging and transformation of the macrophage phenotype. In this way, the synergistic action of the combination of immuno- and chemotherapy of the drug and its carrier on RA was achieved. Our work provides a novel strategy for multisite regulation and controlled management of RA in a noninvasive way.

Correlation between serum IGF-1 and EGF levels and neuropsychiatric and cognitive in Parkinson's disease patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) exert neuroprotective effects in Parkinson's disease (PD). To date, studies on the relationships between serum IGF-1 and EGF levels and nonmotor symptoms in PD patients have been rare. METHODS: A Siemens automatic chemical analyzer was used to determine serum IGF-1 levels, and enzyme-linked immunosorbent assay was used to detect serum EGF levels in 100 healthy controls and 100 PD patients, including those in the early (n = 49) and middle-late (n = 51) stage of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. RESULTS: Serum IGF-1 and EGF levels were higher in PD patients than in healthy controls, and serum IGF-1 and EGF levels were higher in early stage PD patients than in middle-late stage PD patients. Serum IGF-1 levels were significantly negatively correlated with anxiety, depression, and cognitive dysfunction; serum EGF levels were significantly negatively correlated with cognitive dysfunction. Combining IGF-1 and EGF in the diagnosis of PD was more valuable than using a single factor in the diagnosis. CONCLUSIONS: This study shows that serum IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression, and cognitive dysfunction and that EGF levels were correlated with cognitive dysfunction. The combination of IGF-1 and EGF increased the value for a PD diagnosis. This is the first report of the simultaneous detection of IGF-1 and EGF levels to explore the correlation with nonmotor symptoms of PD.

Exploration of the link between gut microbiota and purinergic signalling.

Growing evidence reveals that microorganisms in the gut are linked to metabolic health and disease risk in human beings to a considerable extent. The focus of research at this stage must tend to focus on cause-and-effect studies. In addition to being a component of DNA and RNA, purine metabolites can be involved in purine signalling in the body as chemical messengers. Abnormalities in purinergic signalling may lead to neuropathy, rheumatic immune diseases, inflammation, tumors, and a wide range of other diseases. It has proved that gut microbes are involved in purinergic signalling. The relationship between these gut-derived purinergic signalling molecules and host metabolism may be one of the important clues to our understanding of the mechanisms by which the microbiota affects host metabolism.

A General Signal Pathway to Regulate Multiple Detoxification Genes Drives the Evolution of Helicoverpa armigera Adaptation to Xenobiotics.

The study of insect adaptation to the defensive metabolites of host plants and various kinds of insecticides in order to acquire resistance is a hot topic in the pest-control field, but the mechanism is still unclear. In our study, we found that a general signal pathway exists in H. armigera which can regulate multiple P450s, GSTs and UGTs genes to help insects decrease their susceptibility to xenobiotics. Knockdown of HaNrf2 and HaAhR expression could significantly increase the toxicity of xenobiotics to H. armigera, and simultaneously decrease the gene expression of P450s, GSTs and UGTs which are related to the xenobiotic metabolism and synthesis of insect hormone pathways. Then, we used EMSA and dual luciferase assay to verify that a crosstalk exists between AhR and Nrf2 to regulate multiple P450s, GSTs and UGTs genes to mediate H. armigera susceptibility to plant allelochemicals and insecticides. The detoxification genes' expression network which can be regulated by Nrf2 and AhR is still unknown, and there were also no reports about the crosstalk between AhR and Nrf2 that exist in insects and can regulate multiple detoxification genes' expression. Our results provide a new general signaling pathway to reveal the adaptive mechanism of insects to xenobiotics and provides further insight into designing effective pest-management strategies to avoid the overuse of insecticides.

Deep Eutectic Systems as Novel Vehicles for Assisting Drug Transdermal Delivery.

In recent years, deep eutectic systems (DES) emerged as novel vehicles for facilitating the transdermal delivery of various drugs, including polysaccharides, proteins, insulin, vaccine, nanoparticles, and herb extracts. The objective of this study is to conduct a comprehensive review of the application of DES to transdermal drug delivery, based on previous work and the reported references. Following a brief overview, the roles of DES in TDDS, the modes of action, as well as the structure-activity relationship of DES are discussed. Particularly, the skin permeation of active macromolecules and rigid nanoparticles, which are the defining characteristics of DES, are extensively discussed. The objective is to provide a comprehensive understanding of the current investigation and development of DES-based transdermal delivery systems, as well as a framework for the construction of novel DES-TDDS in the future.

Three-Dimensional Numerical Simulation of Grain Growth during Selective Laser Melting of 316L Stainless Steel.

The grain structure of the selective laser melting additive manufactured parts has been shown to be heterogeneous and spatially non-uniform compared to the traditional manufacturing process. However, the complex formation mechanism of these unique grain structures is hard to reveal using the experimental method alone. In this study, we presented a high-fidelity 3D numerical model to address the grain growth mechanisms during the selective laser melting of 316 stainless steel, including two heating modes, i.e., conduction mode and keyhole mode melting. In the numerical model, the powder-scale thermo-fluid dynamics are simulated using the finite volume method with the volume of fluid method. At the same time, the grain structure evolution is sequentially predicted by the cellular automaton method with the predicted temperature field and the as-melted powder bed configuration as input. The simulation results agree well with the experimental data available in the literature. The influence of the process parameters and the keyhole and keyhole-induced void on grain structure formation are addressed in detail. The findings of this study are helpful to the optimization of process parameters for tailoring the microstructure of fabricated parts with expected mechanical properties.

Detection of Chitin Synthase Mutations in Lufenuron-Resistant Spodoptera frugiperda in China.

Spodoptera frugiperda (J. E. Smith), is commonly known as fall armyworm, native to tropical and subtropical regions of America, is an important migratory agricultural pest. It is important to understand the resistance and internal mechanism of action of S. frugiperda against lufenuron in China. Lufenuron is one of the main insecticides recommended for field use in China and has a broad prospect in the future. We conducted a bioassay using the diet-overlay method and found that the current S. frugiperda in China are still at a low level of resistance to lufenuron. Secondly, we examined whether the mutation I1040M (I1042M in Plutella xylostella), associated with lufenuron resistance, was produced in the field. And then we tested the expression of chitin synthase SfCHSA and SfCHSB in different tissues, and the changes of these two genes after lufenuron induction. The results showed that there is still no mutation generation in China and there is a significant change in the expression of SfCHSA under the effect of lufenuron. In conclusion, our study suggests that field S. frugiperda populations in 2019 and 2020 were less resistant to lufenuron. In fall armyworm, chitin synthases included SfCHSA and SfCHSB genes, and after induction treatment with lufenuron, the expression of the SfCHSA gene was significantly increased. In SfCHSA, no mutation has been detected in the site associated with lufenuron resistance. Secondly, in S. frugiperda larvae, the SfCHSA gene was the highest in the head of the larvae, followed by the integument; while the SfCHSB gene was mainly concentrated in the midgut. Therefore, we believe that the SfCHSA gene plays a greater role in the resistance of S. frugiperda to lufenuron than the SfCHSB gene. It is worth noting that understanding the level of resistance to lufenuron in China, the main mechanism of action of lufenuron on larvae, and the mechanism of resistance to lufenuron in S. frugiperda will help in crop protection as well as in extending the life span of this insecticide.

Nanodelivery System Alters an Insect Growth Regulator's Action Mode: From Oral Feeding to Topical Application.

Insect growth regulators (IGRs) guide animal development through injection, oral feeding, or topical application. Among them, lufenuron is a widely used insect cuticle inhibitor but only shows a gastric toxic effect. Lacking contact toxicity limits the effective utilization when spraying the lufenuron pesticide. To overcome this shortcoming, a nanocarrier (star polycation, SPc)-based transdermal delivery system was applied to improve the penetrability and contact toxicity of lufenuron. The fluoride groups in lufenuron could interact with the tertiary amines in the branch-chain of the SPc through electrostatic interaction to form a lufenuron/SPc complex. The above interaction reduced the particle size of lufenuron from 933 to 70 nm. Interestingly, the contact toxicity of SPc-loaded lufenuron was remarkably improved with effects of higher larval mortality and lower egg hatching rate of the devastating pest fall armyworm. The physiological and molecular toxic mechanism was revealed by RNA-Seq analysis. The SPc-loaded lufenuron apparently down-regulated cuticle-related genes and thus inhibited insect cuticle formation. Such contact toxicity was achieved by the transdermal nanodelivery of lufenuron, which up-regulated endocytosis-related genes for drug uptake. This study is the first successful application of a nanoparticle-mediated transdermal delivery system to explore the contact toxicity of an IGR, which alters the IRG's action mode from oral feeding to topical application.

Insulin-like growth factor in Parkinson's disease is related to nonmotor symptoms and the volume of specific brain areas.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) plays a protective role in Parkinson's disease (PD). To date, studies on the relationship between plasma IGF-1 levels and nonmotor symptoms and brain gray matter volume in PD patients have been rare. METHODS: A Siemens automatic chemical analyzer was used to determine plasma IGF-1 levels in 55 healthy controls and 119 PD patients, including those at the early (n = 67) and middle-late (n = 52) stages of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Image acquisition in 65 PD patients was performed using a Siemens MAGNETOM Prisma 3 T magnetic resonance imaging (MRI) scanner. RESULTS: Plasma IGF-1 levels in early-stage PD patients were higher than those in healthy controls, and plasma IGF-1 levels in early-stage PD patients were higher than those in middle-late-stage PD patients. Plasma IGF-1 levels were significantly negatively correlated with anxiety, depression and cognitive dysfunction. Receiver operating characteristic (ROC) curve assessment confirmed that plasma IGF-1 levels had good predictive accuracy for PD with anxiety, depression and cognitive dysfunction. Furthermore, plasma IGF-1 levels were significantly positively correlated with volumes in the insula, caudate and anterior cingulate. CONCLUSIONS: This study shows that plasma IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression and cognitive dysfunction and the volume in specific brain areas. This is the first report examining the relationships between plasma IGF-1 and clinical manifestations and imaging features in PD patients.

Temperature-Responsive Covalent Organic Framework-Encapsulated Carbon Dot-Based Sensing Platform for Pyrethroid Detection via Fluorescence Response and Smartphone Readout.

In this paper, carbon dot (CD)-encapsulated 1,3,5-tris(4-formylphenyl)benzene (TFB)/2,5-dihydroxyterephthalohydrazide (DHTH) covalent organic frameworks (TDCOFs) grafted with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) (CDs@TDCOFs@PNIPAM) were fabricated for the detection of pyrethroids. CDs@TDCOFs@PNIPAM achieved a temperature-responsive "on/off" detection of pyrethroids based on the target-triggered electron-transfer mechanism. The detection limit of pyrethroids was as low as 0.69 µg/L in the wide linear range of 5-400 µg/L (R2 > 0.9523). Simultaneously, CDs@TDCOFs@PNIPAM with red, green, and blue (RGB) fluorescence emissions were integrated with a smartphone-assisted device, enabling the visual smart quantitative detection of pyrethroids with a detection limit of 4.875 µg/L. Ultimately, agricultural products were chosen as actual samples to verify the applicability of both recognition modes, and the calculated recovery rate was 105.48-113.40%. Accordingly, CDs@TDCOFs@PNIPAM featuring temperature-responsive switching behavior and RGB fluorescence emission provided a promising analytical strategy for ensuring agricultural and food safety.

Plasma arylsulfatase A levels are associated with cognitive function in Parkinson's disease.

BACKGROUND: Arylsulfatase A (ARSA), a lysosomal enzyme, has been shown to inhibit the aggregation and propagation of α-synuclein (α-syn) through its molecular chaperone function. The relationship between ARSA levels and Parkinson's disease (PD) in the Chinese Han population remains controversial, and few quantitative research studies have investigated the relationship between plasma ARSA levels and PD. OBJECTIVES: The purpose of this study was to investigate the relationships between ARSA levels and cognitive function in PD patients and to evaluate the association of ARSA and α-syn levels with nonmotor symptoms. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma ARSA and α-syn levels in 50 healthy controls, 120 PD patients (61 PD patients with no cognitive impairment (PD-NCI) and 59 PD patients with cognitive impairment (PD-CI)). Motor symptoms and nonmotor symptoms (cognitive function, Unified Parkinson's Disease Rating Scale (UPDRS) score, depression, anxiety, constipation, olfactory dysfunction, sleep disruption, and other symptoms) were assessed with the relevant scales. The Kruskal-Wallis H test was used for comparison between groups, and Pearson/Spearman analysis was used for correlation analysis. RESULTS: The plasma ARSA concentrations were lower in the PD-CI group than in the PD-NCI group. The plasma α-syn levels in the PD-CI group were higher than those in the healthy control group, and the plasma ARSA levels were correlated with the Mini-Mental State Examination (MMSE scores) and Hoehn and Yahr (H-Y) stage. CONCLUSION: We used a quantitative assessment method to show that low plasma ARSA levels and high α-syn levels are related to cognitive impairment in PD patients. Plasma ARSA levels gradually decrease with PD progression.

Inhibition of ERK1/2 regulates cognitive function by decreasing expression levels of PSD-95 in the hippocampus of CIH rats.

Obstructive sleep apnoea syndrome (OSAS) is a potentially severe sleep disorder characterized by intermittent hypoxia, and there is growing evidence that OSAS can lead to cognitive decline. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) plays a key role in synaptic plasticity. We established CIH model in male SD rats and examined their expression of p-ERK1/2 and PSD-95, as well as in CIH group; the effect of SL327 on the expression of p-ERK1/2 and PSD-95 in hippocampus of CIH model rats was observed by pretreating the experimental rats with SL327 during peak time of p-ERK1/2 expression. Mean oxygen saturation in the tail artery was lower in the CIH group. CIH groups exhibited increased escape latencies in the navigation test and decreased numbers of platform crossings in the space exploration test. Reduced volume, irregular structure, deepened cytoplasmic eosinophilic staining in the cytoplasm and decreased nuclear size were found in hippocampal neurons in the 28-d CIH and 28-d CIH + SL327 group. The hippocampus of CIH rats' p-ERK expressions gradually increased with prolonged CIH exposure but decreased after SL327 treatment. Moreover, PSD-95 expressions gradually reduced in the 14-d CIH, 21-d CIH and 28-d CIH groups but increased in the SL327-treated group. The SL327 intervention decreased p-ERK1/2 expression, increased PSD-95 expression and improved cognitive function in CIH rats. The present findings provide some insights into the mechanisms underlying OSAS-associated cognitive impairment.