Assessing of case-cohort design: a case study for breast cancer patients in Xinjiang, China.

Objective: To assess the effectiveness and clinical value of case-cohort design and determine prognostic factors of breast cancer patients in Xinjiang on the basis of case-cohort design. Methods: The survival data with different sample characteristics were simulated by using Cox proportional risk models. To evaluate the effectiveness for the case-cohort, entire cohort, and simple random sampling design by comparing the mean, coefficient of variation, etc., of covariate parameters. Furthermore, the prognostic factors of breast cancer patients in Xinjiang were determined based on case-cohort sampling designs. The models were comprehensively evaluated by likelihood ratio test, the area under the receiver operating characteristic curve (AUC), and Akaike Information Criterion (AIC). Results: In a simulations study, the case-cohort design shows better stability and improves the estimation efficiency when the censored rate is high. In the breast cancer data, molecular subtypes, T-stage, N-stage, M-stage, types of surgery, and postoperative chemotherapy were identified as the prognostic factors of patients in Xinjiang. These models based on the different sampling designs both passed the likelihood ratio test (p<0.05). Moreover, the model constructed under the case-cohort design had better fitting effect (AIC=3,999.96) and better discrimination (AUC=0.807). Conclusion: Simulations study confirmed the effectiveness of case-cohort design and further determined the prognostic factors of breast cancer patients in Xinjiang based on this design, which presented the practicality of case-cohort design in actual data.

Exercised-enriched blood plasma rescues hippocampal impairments and cognitive deficits in an Alzheimer's disease model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and moderate exercise holds promise in ameliorating the ongoing neurodegeneration and cognitive decline. Here, we investigated whether exercise-enriched blood plasm could yield a beneficial therapeutic effect on AD pathologies and cognitive decline in transgenic AD (P301S) mice. In this investigation, a cohort of 2-month-old C57BL/6 mice were granted continuous access to either a running wheel or a fixed wheel for 6 weeks. After that, their plasmas were extracted and subsequently injected intravenously into 4.5-month-old P301S mice biweekly over a 6-week period. A comprehensive methodology was then employed, integrating behavioral tests, pathology assessments, and biochemical analyses to unveil the potential anti-dementia implications of exercise-enriched blood plasma in P301S mice. Upon systemic administration, the findings revealed a noteworthy attenuation of hippocampus-dependent behavioral impairments in P301S mice. Conversely, blood plasma from sedentary counterparts exhibited no discernible impact. These effects were intricately associated with the mitigation of neuroinflammation, the augmentation of hippocampal adult neurogenesis, and a reduction of synaptic impairments following the administration of exercise-enriched blood plasma. These findings advance the proposition that administering exercise-enriched blood plasma may serve as an effective prophylactic measure against AD, opening avenues for further exploration and potential therapeutic interventions.

Modelling of tuberculosis dynamics incorporating indirect transmission of contaminated environment and infectivity of smear-negative individuals: A case study for Xinjiang, China.

Xinjiang has been one of the high incidence areas of pulmonary tuberculosis (PTB) in China. Besides being infected by direct contacting with active PTB individuals (direct infection), the susceptible would be infected because of the exposure to the environment contaminated by Mycobacterium tuberculosis (indirect infection). Active PTB individuals include not only the smear-positive PTB (PTB+) but also the smear-negative PTB (PTB-) who are infectious due to their ability to release tiny Mycobacterium tuberculosis particles even in the absence of visible Mycobacterium tuberculosis in sputum. By taking account of direct/indirect infection and the difference between PTB+ and PTB- individuals in transmission capability, a periodic dynamical PTB transmission model is proposed. The model is fitted to the newly monthly PTB+ and PTB- cases in Xinjiang from 2008 to 2017 by Markov Chain Monte Carlo algorithm. Moreover, global sensitivity analysis is constructed to address the uncertainty of some key parameters by using Latin hypercube sampling and partial rank correlation coefficient methods. Basic reproduction number R0 for PTB transmission in Xinjiang is estimated to be 2.447 (95% CrI:(1.203, 3.844)), indicating that PTB has been prevalent in Xinjiang over the study period. Our results suggest that reducing the direct/indirect transmission rates, early screening, isolating and treating the latent, PTB+ and PTB- individuals, and enhancing the clearance of Mycobacterium tuberculosis in the environment could more effectively control PTB transmission in Xinjiang. The model fits the reported PTB data well and achieves acceptable prediction accuracy. We believe that our model can provide heuristic support for controlling PTB transmission in Xinjiang.

P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice.

OBJECTIVE: Post-stroke cognitive impairment (PSCI) develops in approximately one-third of stroke survivors and is associated with ingravescence. Nonetheless, the biochemical mechanisms underlying PSCI remain unclear. The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions (MCAOs) and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5 (CDK5)-mediated tau hyperphosphorylation on the PSCI behavior. METHODS: Cognitive behavior was investigated, followed by the detection of tau hyperphosphorylation, mobilization, activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice. Finally, we treated HEK293/tau cells with oxygen-glucose deprivation (OGD) and a CDK5 inhibitor (Roscovitine) or a GSK3ß inhibitor (LiCl) to the roles of CDK5 and GSK3ß in mediating ischemia-reperfusion-induced tau phosphorylation. RESULTS: Ischemia induced cognitive impairments within 2 months, as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra. Furthermore, p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation (control) group, while the expression levels of protein phosphatase 2 (PP2A) and the phosphorylation level at Tyr307 were comparable between the two groups. In addition, the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD. CONCLUSION: These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra, contributing to the pathogenesis of PSCI.

BACE1 SUMOylation deregulates phosphorylation and ubiquitination in Alzheimer's disease pathology.

BACE1 is essential for the generation of amyloid-ß (Aß) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the relationship between these modifications is not fully characterized. Here, we studied the effects of BACE1 SUMOylation on its phosphorylation and ubiquitination. We demonstrate that SUMOylation of BACE1 inhibits its phosphorylation at S498 and its ubiquitination in vitro. Conversely, BACE1 phosphorylation at S498 suppresses its SUMOylation, which results in promoting BACE1 degradation in vitro. Furthermore, an increase in BACE1 SUMOylation is associated with the progression of AD pathology, while its phosphorylation and ubiquitination are decreased in an AD mouse model. Our findings suggest that BACE1 SUMOylation reciprocally influences its phosphorylation and competes against its ubiquitination, which might provide a new insight into the regulations of BACE1 activity and Aß accumulation.

Microporous metallic scaffolds supported liquid infused icephobic construction.

HYPOTHESIS: Ice accretion on component surfaces often causes severe impacts or accidents. Liquid-infused surfaces (LIS) have drawn much attention as icephobic materials for ice mitigation in recent years due to their outstanding icephobicity. However, the durability of LIS constructions remains a big challenge, including mechanical vulnerability and rapid depletion of lubricants. The practical applications of LIS materials are significantly restrained, and the full potential of LIS for ice prevention has yet to be demonstrated. EXPERIMENTS: A universal approach was proposed to introduce microporous metallic scaffolds in the LIS construction to increase the applicability and durability, and to prompt the potential of LIS for ice mitigation. Microporous Ni scaffolds were chosen to integrate with polydimethylsiloxane modified by silicone oil addition. FINDINGS: The new LIS construction demonstrated significantly improved durability in icing/de-icing cyclic test, and it also offered a solution for the rapid oil depletion by restraining the deformation of the matrix material. Low ice adhesion strength could be maintained via a micro-crack initiation mechanism. The results indicated that the multi-phase LIS construction consisting of microporous Ni scaffolds effectively addressed the shackles of the icephobicity deterioration of LIS materials, confirming a new design strategy for the R&D of icephobic surfaces.

A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days.

Background: Due to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection. Objectives: To evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens. Methods: A prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days. Results: The neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)). Conclusions: Compared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.

Histology, ultrastructure, and differential gene expression in relation to seasonal sperm storage in the oviduct of the Chinese alligator, Alligator sinensis.

Although oviductal sperm storage are essential steps in reproduction for female animals with internal fertilisation, no systematic study on the identification of genes involving sperm storage has been performed in crocodilian species. In the present research, the relationship between morphological variation related to sperm storage in the oviduct and gene expression patterns derived from RNA sequencing analyses between active period (AP), breeding period (BP), and hibernation period (HP) were investigated. The corresponding results indicated that sperm were observed not only in the ciliated cells within infundibulum and mucosal layer of uterus during BP, but also been detected in the spermatosperm storage tube (SST) in the anterior uterus at HP stage. The further transmission electron microscopy analysis indicated that the differences in the number and activity of the secretory cells likely to attributed to the seasonal variation of microenvironment related to the sperm storage. Based on the RNA-sequecing, 13147 DEGs related to the Peroxisome proliferator-activated receptors (PPARs) and FOXO signalling were identified, including these, the down-regulated ATG12 and BCL2L11 in the HP group may thus constitute an important point of convergence between autophagy and apoptosis involving the FOXO1 pathway. The genes involved in the PPARs pathway might modulate the immune response and thereby contribute to prolong the life span of stored spermatozoa in Alligator sinensis . The outcomes of this study provide fundamental insights into the mechanism of sperm storage in A. sinensis .

Stereoselective Total Syntheses of C18-Oxo Eburnamine-Vincamine Alkaloids.

Here, we disclose the divergent total syntheses of representative C18-oxo eburnamine-vincamine alkaloids (+)-eburnaminol, (-)-larutenine, and (-)-cuanzine. Key to the approach is a substrate-controlled iridium-catalyzed asymmetric hydrogenation/lactamization cascade that leads to the formation of the common tetracyclic skeleton with essential cis-C20/C21 stereochemistry (93% yield, 98% ee, >20:1 dr, gram scale). Access to the targeted alkaloids is effected late in the synthesis by implementation of a number of diversity-oriented transformations and late-stage modifications.

The total synthesis of (-)-strempeliopine via palladium-catalyzed decarboxylative asymmetric allylic alkylation.

In the work reported herein, the concise and enantioselective total synthesis of the Schizozygine alkaloid (-)-strempeliopine was developed. This synthetic strategy featured the palladium-catalyzed decarboxylative asymmetric allylic alkylation of N-benzoyl lactam to set up the absolute configuration at the C20 position, a highly diastereoselective one-pot Bischler-Napieralski/lactamization and iminium reduction sequence for the construction of the pentacyclic core structure, and the late-stage dearomative addition of indole, leading to the otherwise difficult-to-achieve hexacyclic indoline framework with complete control of four neighbouring stereocenters.

Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice.

Tangeretin (TAN) exhibits many bioactivities, including neuroprotective effects. However, the efficacy of TAN in Alzheimer's disease (AD) has not been sufficiently investigated. In the present study, we integrated behavioral tests, pathology assessment, and biochemical analyses to elucidate the antidementia activity of TAN in APPswe/PSEN1dE9 transgenic (Tg) mice. At supplementation levels of 100 mg/kg body weight per day, TAN significantly attenuated the cognitive impairment of Tg mice in behavioral tests. These effects were associated with less synaptic impairments and fewer ß-amyloid accumulations after TAN administration. Furthermore, our study revealed that TAN possessed powerful inhibitory activity against ß-secretase both in vitro and in vivo, which played a crucial role in the process of Aß generation. These findings indicate that TAN is a potential drug for preventing AD pathology. The key mechanism underlying the antidementia effect of TAN may include its inhibitory activity against ß-secretase.

Spatial Training Attenuates Long-Term Alzheimer's Disease-Related Pathogenic Processes in APP/PS1 Mice.

BACKGROUND: Alzheimer's disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-ß (Aß) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aß deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated. OBJECTIVE: To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice. METHODS: We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence. RESULTS: One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aß deposition and decrease the expression of ß-secretase (BACE1) and amyloid-ß protein precursor (AßPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage. CONCLUSION: Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.

Prognostic analysis of breast cancer in Xinjiang based on Cox proportional hazards model and two-step cluster method.

Objective: To examine the factors that affect the prognosis and survival of breast cancer patients who were diagnosed at the Affiliated Cancer Hospital of Xinjiang Medical University between 2015 and 2021, forecast the overall survival (OS), and assess the clinicopathological traits and risk level of prognosis of patients in various subgroups. Method: First, nomogram model was constructed using the Cox proportional hazards models to identify the independent prognostic factors of breast cancer patients. In order to assess the discrimination, calibration, and clinical utility of the model, additional tools such as the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA) were used. Finally, using two-step cluster analysis (TCA), the patients were grouped in accordance with the independent prognostic factors. Kaplan-Meier survival analysis was employed to compare prognostic risk among various subgroups. Result: T-stage, N-stage, M-stage, molecular subtyping, type of operation, and involvement in postoperative chemotherapy were identified as the independent prognostic factors. The nomogram was subsequently constructed and confirmed. The area under the ROC curve used to predict 1-, 3-, 5- and 7-year OS were 0.848, 0.820, 0.813, and 0.791 in the training group and 0.970, 0.898, 0.863, and 0.798 in the validation group, respectively. The calibration curves of both groups were relatively near to the 45° reference line. And the DCA curve further demonstrated that the nomogram has a higher clinical utility. Furthermore, using the TCA, the patients were divided into two subgroups. Additionally, the two groups' survival curves were substantially different. In particular, in the group with the worse prognosis (the majority of patients did not undergo surgical therapy or postoperative chemotherapy treatment), the T-, N-, and M-stage were more prevalent in the advanced, and the total points were likewise distributed in the high score side. Conclusion: For the survival and prognosis of breast cancer patients in Xinjiang, the nomogram constructed in this paper has a good prediction value, and the clustering results further demonstrated that the selected factors were important. This conclusion can give a scientific basis for tailored treatment and is conducive to the formulation of focused treatment regimens for patients in practical practice.

High Fat Diet Aggravates AD-Related Pathogenic Processes in APP/PS1 Mice.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder and negative lifestyle factors may contribute to its etiopathogenesis. Substantial evidence from humans and murine models reveals that Insulin Resistance (IR) associated with a high fat diet (HFD) increases the risk of developing AD and age-related amyloidogenesis. OBJECTIVE: The aim of the study was to corroborate and clarify the influence of HFD on amyloidogenesis and cognitive deficits in AD model mice. METHODS: We here show that a four months HFD-feeding increases IR in both the periphery and brain of APP/PS1 mice, which are used as AD models. Meanwhile, long-term HFD exacerbates cognitive defects and impairs dendritic integrity and expressions of synaptic proteins in APP/PS1 mice. Furthermore, HFD induces an increase in ß-secretase (BACE1) expression and a decrease in insulin-degrading enzyme (IDE) expression, resulting in ß-amyloid (Aß) accumulation. CONCLUSION: Our data suggest that long-term HFD, with the accompanying IR, promotes Aß toxicity and cognitive deficits, indicating that modifiable lifestyle hazards such as HFD-induced IR might contribute to AD pathogenesis.

Elavl2 Regulates Retinal Function Via Modulating the Differentiation of Amacrine Cells Subtype.

Purpose: The neuronal ELAV-like proteins (nElavls; Elavl2, Elavl3, Elavl4) have been known to regulate neuronal differentiation, maintenance, and axonogenesis in the brain. However, the specific role of nElavls in retina remains unclear. Here, we attempted to identify the expression pattern of Elavl2 during retinogenesis and aimed to decipher the function of Elavl2 in the retina. Methods: We have used the Cre-loxP system to conditionally inactivate Elavl2 in order to examine its role in developing retina. Eyes were collected for histology, immunohistochemistry, and TUNEL analysis to identify the structure of retina, and examined by RNA sequencing to analyze the function and pathway enrichment of differentially expressed genes in transgenic mice. Moreover, the mechanism by which Elavl2 regulates the differentiation of amacrine cells (ACs) was explored by RNA immunoprecipitation assays. Finally, eyes were functionally assessed by whole-cell patch-clamp, electroretinography (ERG) and optomotor response. Results: Elavl2 was expressed in retinal progenitor cells and retinal ganglion cells (RGCs), ACs, and horizontal cells. Retina-specific ablation of Elavl2 led to the loss of ACs and the transcription factors involved in ACs differentiation were also downregulated. In addition, the spontaneous activities of RGCs were obviously increased in Elavl2-deficient mice. Meanwhile, the loss of ACs that induced by Elavl2 deficiency lead to a decrease in ERG responses and visual acuity. Conclusions: Elavl2 is an intrinsic factor that involved in the differentiation of ACs subtype during retinogenesis, and essential for maintaining the normal retinal function.

Metallic skeleton promoted two-phase durable icephobic layers.

HYPOTHESIS: The accretion of ice on component surfaces often causes severe impacts or accidents in modern industries. Applying icephobic surface is considered as an effective solution to minimise the hazards. However, the durability of the current icephobic surface and coatings for long-term service remains a great challenge. Therefore, it is indeed to develop new durable material structures with great icephobic performance. EXPERIMENTS: A new design concept of combining robust porous metallic skeletons and icephobic filling was proposed. Nickel/polydimethylsiloxane (PDMS) two-phase layer was prepared using porous Ni foam skeletons impregnated with PDMS as filling material by a two-step method. FINDINGS: Good icephobicity and mechanical durability have been verified. Under external force, micro-cracks could easily initiate at the ice/solid interface due to the small surface cavities and the difference of local elastic modulus between the ice and PDMS, which would promote the ice fracture and thus lead to low ice adhesion strength. The surface morphology and icephobicity almost remain unchanged after water-sand erosion, showing greatly improved mechanical durability. By combining the advantages of the mechanical durability of porous Ni skeleton and the icephobicity of PDMS matrix, the Ni foam/PDMS two-phase layer demonstrates great potentials for ice protection with long-term service time.

Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days.

Background: A vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators. Objectives: To evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection. Methods: We determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence. Results: The seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00-244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62-30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (>31 years) (P<0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P<0.05). Conclusions: Antibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.

Epigallocatechin-3-gallate Alleviates Cognitive Deficits in APP/PS1 Mice.

Alzheimer's disease (AD) shows cognitive impairments in clinic, which is multifactorial with different etiopathogenic mechanisms such as Aß deposition, neuroinflammation and neuronal dystrophy involved. Therefore, multi-targets drugs with neuroprotective, anti-amyloidogenic and anti-inflammatory properties will be effective in AD treatment. Epigallocatechin-3-gallate (EGCG) possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative diseases. In the present study, we showed that oral administration of EGCG (50 mg/kg) for 4 months significantly attenuated the cognitive deficits in APP/PS1 transgenic mice, which served as AD model. Moreover, EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS1 mice. And EGCG exerted obvious anti-inflammatory effects, which was manifested by alleviating microglia activation, decreasing pro-inflammatory cytokine (IL-1ß) and increasing anti-inflammatory cytokines (IL-10, IL-13). Furthermore, ß-amyloid (Aß) plaques were markedly reduced in the hippocampus of 6-month old APP/PS1 mice after EGCG treatment. In conclusion, these findings indicate that EGCG improves AD-like cognitive impairments through neuroprotective, anti-amyloidogenic and anti-inflammatory effects, thus is a promising therapeutic candidate for AD.