The dual-specificity kinase MoLKH1-mediated cell cycle, autophagy, and suppression of plant immunity is critical for development and pathogenicity of Magnaporthe oryzae.

Cell cycle progression, autophagic cell death during appressorium development, and ROS degradation at the infection site are important for the development of rice blast disease. However, the association of cell cycle, autophagy and ROS detoxification remains largely unknown in M. oryzae. Here, we identify the dual-specificity kinase MoLKH1, which serves as an important cell cycle regulator required for appressorium formation by regulating cytokinesis and cytoskeleton in M. oryzae. MoLKH1 is transcriptionally activated by H2O2 and required for H2O2-induced autophagic cell death and suppression of ROS-activated plant defense during plant invasion of M. oryzae. In addition, the Molkh1 mutant also showed several phenotypic defects, including delayed growth, abnormal conidiation, damaged cell wall integrity, impaired glycogen and lipid transport, reduced secretion of extracellular enzymes and effectors, and attenuated virulence of M. oryzae. Nuclear localization of MoLKH1 requires the nuclear localization sequence, Lammer motif, as well as the kinase active site and ATP-binding site in this protein. Site-directed mutagenesis showed that each of them plays crucial roles in fungal growth and pathogenicity of M. oryzae. In conclusion, our results demonstrate that MoLKH1-mediated cell cycle, autophagy, and suppression of plant immunity play crucial roles in development and pathogenicity of M. oryzae.

Robust internal model control based on a novel generalized extended state observer and its application on a two-inertia system.

Disturbance observer (DOB) and extended state observer (ESO) are extensively utilized to handle external disturbances and model uncertainties in the control system. Nevertheless, the integration of these two methods to improve disturbance suppression remains an open question. In this research, the disturbance compensation mechanism of DOB is employed to compensate the disturbance estimation error of ESO, thereby achieving an effective integration of DOB and ESO. Additionally, a generalized ESO (GESO) is proposed to replace ESO. A robust internal mode control (RIMC) scheme is then developed by incorporating GESO into a two-degree-of-freedom internal mode control (TDF-IMC) framework. Moreover, the equivalence of RIMC and classical TDF-IMC is given by a rigorous derivation under the frequency domain description. Finally, the RIMC is applied to the control of a two-inertia system to verify its superiority in terms of robustness, disturbance rejection, and resonance suppression.

[Anti-inflammatory effect and its mechanism of Saracae Cortex based on zebrafish model and network pharmacology].

This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

Feasibility of 129I groundwater dating calibrated by both 81Kr and 4He for the assessment of deep geological repositories in Japan.

Iodine-129, which is a promising tracer for dating old groundwater, has been used as a tracer for deep upwelling groundwater. The nuclide is expected to be one of the key factors for site selection for high-level radioactive waste disposal, which is a global societal issue. The pre-anthropogenic 129I/127I ratio for marine iodine is (1.50 ± 0.15) × 10-12, which could be considered the initial value for 129I dating. This study identifies the challenges in groundwater age dating using 129I/127I. We measured the ratios of 129I/127I and 81Kr/Kr and concentration of 4He in groundwater from boreholes on the northern coast of Japan. The 129I dating results were not coincident with the other groundwater dating results. The iodine in the groundwater was inferred to be released in situ from marine organisms in sediments of various ages. We estimated that the primordial iodine ratio originating from seawater was ~ 1 × 10-13 (8 × 10-14 ~ 2 × 10-13). The groundwater age deduced from the 129I/127I ratio using this value agrees with other groundwater dating results.

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain.

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.

Dual-band frequency reconfigurable metasurface antenna for millimeter wave joint communication and radar sensing systems.

This paper introduces an innovative, compact, and high-gain metasurface antenna, covering both the 24 GHz millimeter wave (mmWave) radar band and the 5 G n257 and n258 bands. The proposed metasurface antenna consists of a wideband stacked patch antenna and a dual-layer metasurface to focus its radiation beams for multiple mmWave bands. The operating frequency can be slightly shifted by altering the distance between the feeder and the metasurface. The distribution of the metasurface unit cells is designed based on a simplified phase compensation formula. The dimension of the fabricated feeder is 6 mm × 6 mm, and the metasurface occupies a 65 mm × 65 mm radome area. Experimental results demonstrate a wide bandwidth from 23.5 GHz to 29.1 GHz for the feeder, and impressive maximum gains of 19.7 dBi and 19.5 dBi for the lower band and higher band of the metasurface antenna are achieved simultaneously. The frequency reconfiguration ability was characterized by a 750 MHz frequency shift with every 1 mm distance adjustment. The compact size and high gain performance of the proposed design underscore its potential for practical applications in millimeter wave joint communication and radar sensing systems.

Rhodiola rosea: a review in the context of PPPM approach.

A natural "medicine and food" plant, Rhodiola rosea (RR) is primarily made up of organic acids, phenolic compounds, sterols, glycosides, vitamins, lipids, proteins, amino acids, trace elements, and other physiologically active substances. In vitro, non-clinical and clinical studies confirmed that it exerts anti-inflammatory, antioxidant, and immune regulatory effects, balances the gut microbiota, and alleviates vascular circulatory disorders. RR can prolong life and has great application potential in preventing and treating suboptimal health, non-communicable diseases, and COVID-19. This narrative review discusses the effects of RR in preventing organ damage (such as the liver, lung, heart, brain, kidneys, intestines, and blood vessels) in non-communicable diseases from the perspective of predictive, preventive, and personalised medicine (PPPM/3PM). In conclusion, as an adaptogen, RR can provide personalised health strategies to improve the quality of life and overall health status.

Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation.

White matter hyperintensities (WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216-mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216-mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.

Systematic review and meta-analysis of short-term outcomes: robot-assisted versus laparoscopic surgery for gastric cancer patients with visceral obesity.

The objective of this meta-analysis was to assess the comparative efficacy of robot-assisted and laparoscopic surgery in treating gastric cancer among patients characterized by a high visceral fat area (VFA). In April 2024, we conducted a comprehensive literature review using major international databases, such as PubMed, Embase, and Google Scholar. We restricted our selection to articles written in English, excluding reviews, protocols without published data, conference abstracts, and irrelevant content. Our analysis focused on continuous data using 95% confidence intervals (CIs) and standard mean differences (SMDs), while dichotomous data were assessed with odds ratios (ORs) and 95% CIs. We set the threshold for statistical significance at P < 0.05. Data extraction included baseline characteristics, primary outcomes (such as operative time, major complications, lymph node yield, and anastomotic leakage), and secondary outcomes. The meta-analysis included three cohort studies totaling 970 patients. The robotic-assisted group demonstrated a significantly longer operative time compared to the laparoscopic group, with a weighted mean difference (WMD) of - 55.76 min (95% CI - 74.03 to - 37.50; P < 0.00001). This group also showed a reduction in major complications, with an odds ratio (OR) of 2.48 (95% CI 1.09-5.66; P = 0.03) and fewer occurrences of abdominal infections (OR 3.17, 95% CI 1.41-7.14; P = 0.005), abdominal abscesses (OR 3.83, 95% CI 1.53-9.57; P = 0.004), anastomotic leaks (OR 4.09, 95% CI 1.73-9.65; P = 0.001), and pancreatic leaks (OR 8.93, 95% CI 2.33-34.13; P = 0.001). However, no significant differences were observed between the groups regarding length of hospital stay, overall complications, estimated blood loss, or lymph node yield. Based on our findings, robot-assisted gastric cancer surgery in obese patients with visceral fat appears to be correlated with fewer major complications compared to laparoscopic surgery, while maintaining similar outcomes in other surgical aspects. However, it is important to note that robot-assisted procedures do tend to have longer operative times.

TLTNet: A novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation.

Extracting global and local feature information is still challenging due to the problems of retinal blood vessel medical images like fuzzy edge features, noise, difficulty in distinguishing between lesion regions and background information, and loss of low-level feature information, which leads to insufficient extraction of feature information. To better solve these problems and fully extract the global and local feature information of the image, we propose a novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation, which consists of an encoder and a decoder and is connected between the encoder and decoder by a transscale transformer cascade module. Among them, the encoder consists of a local-global transscale transformer module, a multi-head layered transscale adaptive embedding module, and a local context(LCNet) module. The transscale transformer cascade module learns local and global feature information from the first three layers of the encoder, and multi-scale dependent features, fuses the hierarchical feature information from the skip connection block and the channel-token interaction fusion block, respectively, and inputs it to the decoder. The decoder includes a decoding module for the local context network and a transscale position transformer module to input the local and global feature information extracted from the encoder with retained key position information into the decoding module and the position embedding transformer module for recovery and output of the prediction results that are consistent with the input feature information. In addition, we propose an improved cross-entropy loss function based on the difference between the deterministic observation samples and the prediction results with the deviation distance, which is validated on the DRIVE and STARE datasets combined with the proposed network model based on the dual transformer structure in this paper, and the segmentation accuracies are 97.26% and 97.87%, respectively. Compared with other state-of-the-art networks, the results show that the proposed network model has a significant competitive advantage in improving the segmentation performance of retinal blood vessel images.

Research on Foot Contact State Detection Technology of Wheel-Legged Robot.

The accurate perception of external environment information through the robot foot is crucial for the mobile robot to evaluate its ability to traverse terrain. Adequate foot-end contact signals can provide robust support for robot motion control and decision-making processes. The shape and uncertain rotation of the wheel-legged robot foot end represent a significant challenge to sensing the robot foot-end contact state, which current foot-end sensing schemes cannot solve. This paper presents a sensing method for the tire stress field of wheel-legged robots. A finite element analysis was conducted to study the deformation characteristics of the foot-end tire under force. Based on this analysis, a heuristic contact position estimator was designed that utilizes symmetrical deformation characteristics. Strain sensors, arranged in an array, extract the deformation information on the inner surface of the tire at a frequency of 200 Hz. The contact position estimator reduces the dimensionality of the data and fits the eigenvalues to the estimated contact position. Using support vector regression, the force estimator utilizes the estimated contact position and sensor signal to estimate the normal reaction force, designated as FZ. The sensing system is capable of detecting the contact position on the wheel circumference (with a root mean square error of 1.150°), as well as the normal force of 160 N on the Z axis (with a root mean square error of 6.04%). To validate the efficacy of the sensor detection method, a series of randomized and repeated experiments were conducted on a self-constructed test platform. This novel approach offers a promising avenue for perceiving contact states in wheel-legged robots.

DDAH-1 maintains endoplasmic reticulum-mitochondria contacts and protects dopaminergic neurons in Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra is a hallmark of pathology in Parkinson's disease (PD). Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the critical enzyme responsible for the degradation of asymmetric dimethylarginine (ADMA) which inhibits nitric oxide (NO) synthase and has been implicated in neurodegeneration. Mitochondrial dysfunction, particularly in the mitochondria-associated endoplasmic reticulum membrane (MAM), plays a critical role in this process, although the specific molecular target has not yet been determined. This study aims to examine the involvement of DDAH-1 in the nigrostriatal dopaminergic pathway and PD pathogenesis. The distribution of DDAH-1 in the brain and its colocalization with dopaminergic neurons were observed. The loss of dopaminergic neurons and aggravated locomotor disability after rotenone (ROT) injection were showed in the DDAH-1 knockout rat. L-arginine (ARG) and NO donors were employed to elucidate the role of NO respectively. In vitro, we investigated the effects of DDAH-1 knockdown or overexpression on cell viability and mitochondrial functions, as well as modulation of ADMA/NO levels using ADMA or ARG. MAM formation was assessed by the Mitofusin2 oligomerization and the mitochondrial ubiquitin ligase (MITOL) phosphorylation. We found that DDAH-1 downregulation resulted in enhanced cell death and mitochondrial dysfunctions, accompanied by elevated ADMA and reduced NO levels. However, the recovered NO level after the ARG supplement failed to exhibit a protective effect on mitochondrial functions and partially restored cell viability. DDAH-1 overexpression prevented ROT toxicity, while ADMA treatment attenuated these protective effects. The declines of MAM formation in ROT-treated cells were exacerbated by DDAH-1 downregulation via reduced MITOL phosphorylation, which was reversed by DDAH-1 overexpression. Together, the abundant expression of DDAH-1 in nigral dopaminergic neurons may exert neuroprotective effects by maintaining MAM formation and mitochondrial function probably via ADMA, indicating the therapeutic potential of targeting DDAH-1 for PD.

Design of an optical passive semi-athermalization zoom lens.

Traditional zoom lenses cannot clearly image during the entire zoom process when the ambient temperature changes and needs to focus frequently at middle focal length positions. An innovative design method called the optical passive semi-athermalization (OPSA) design for zoom optical systems is proposed which, based on the difference in the focusing sensitivity of the focusing group at short and long focal length positions, seeks out sensitive groups that have a greater impact on the imaging quality at the short focal position. By changing the temperature characteristics of the temperature-sensitive lenses in these groups, an OPSA zoom optical system can be realized, which exhibits a compact structure and excellent imaging quality. Under the ambient temperature of -40∘ C to +60∘ C, the OPSA zoom lens needs to refocus only once at the long focal length position, which can ensure an image clearly during the entire zoom process. Remarkably, this innovative method not only mitigates the frequent focusing challenges in traditional zoom lenses, but also contributes to the diminutive size.

Compensated DOE in a VHG-based waveguide display to improve uniformity.

Augmented reality head-mounted displays (AR-HMDs) utilizing diffractive waveguides have emerged as a popular research focus. However, the illuminance uniformity over the fields of view (FOV) is often unsatisfactory in volume holographic grating (VHG) based waveguide displays. This paper proposes a high uniformity AR waveguide display system. Firstly, the angular uniformity of the VHG-based waveguide displays is analyzed. Subsequently, diffractive optical elements (DOEs) are seamlessly integrated onto the outer coupling surface of the waveguide substrate to improve the angular uniformity through phase compensation. To design the DOE phase, the multi-objective stochastic gradient descent (MO-SGD) algorithm is proposed. A single DOE is used to compensating various images form the image source. A hybrid loss, which includes the learned perceptual image patch similarity (LPIPS) metric, is applied to enhance the algorithm performance. Simulation results show that the proposed method effectively suppresses illumination degradation at the edge FOV in exit pupil images of the waveguide display system. In the results, the peak signal-to-noise ratio (PSNR) is improved by 5.54 dB. Optical experiments validate the effectiveness of the proposed method. The measured nonuniformity (NU) against FOVs is improved by 53.05% from 0.3749 to 0.1760.

Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China.

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

The MAP kinase FvHog1 regulates FB1 synthesis and Ca2+ homeostasis in Fusarium verticillioides.

The high osmolarity glycerol 1 mitogen-activated protein kinase (Hog1-MAPK) cascade genes are important for diverse biological processes. The activated Hog1 upon multiple environmental stress stimuli enters into the nucleus where it directly phosphorylates transcription factors to regulate various physiological processes in phytopathogenic fungi. However, their roles have not been well-characterized in Fusarium verticillioides. In this study, FvHog1 is identified and functionally analyzed. The findings reveal that the phosphorylation level and nuclear localization of FvHog1 are increased in Fumonisin B1 (FB1)-inducing condition to regulate the expression of FB1 biosynthesis FUM genes. More importantly, the deletion mutants of Hog1-MAPK pathway show increased sensitivity to Ca2+ stress and elevated intracellular Ca2+ content. The phosphorylation level and nuclear localization of FvHog1 are increased with Ca2+ treatment. Furthermore, our results show that FvHog1 can directly phosphorylate Ca2+-responsive zinc finger transcription factor 1 (FvCrz1) to regulate Ca2+ homeostasis. In conclusion, our findings indicate that FvHog1 is required for FB1 biosynthesis, pathogenicity and Ca2+ homeostasis in F. verticillioides. It provides a theoretical basis for effective prevention and control maize ear and stalk rot disease.

Three-dimensional spatio-angular fluorescence microscopy with a polarized dual-view inverted selective-plane illumination microscope (pol-diSPIM).

Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the three-dimensional orientations and diffraction-limited positions of ensembles of fluorescent dipoles that label biological structures, and we share a set of visualization, histogram, and profiling tools for interpreting these positions and orientations. We model our samples, their excitation, and their detection using coarse-grained representations we call orientation distribution functions (ODFs). We apply ODFs to create physics-informed models of image formation with spatio-angular point-spread and transfer functions. We use theory and experiment to conclude that light-sheet tilting is a necessary part of our design for recovering all three-dimensional orientations. We use our system to extend known two-dimensional results to three dimensions in FM1-43-labelled giant unilamellar vesicles, fast-scarlet-labelled cellulose in xylem cells, and phalloidin-labelled actin in U2OS cells. Additionally, we observe phalloidin-labelled actin in mouse fibroblasts grown on grids of labelled nanowires and identify correlations between local actin alignment and global cell-scale orientation, indicating cellular coordination across length scales.

Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells.

Alzheimer's disease is characterized by abnormal ß-amyloid and tau accumulation, mitochondrial dysfunction, oxidative stress, and synaptic dysfunction. Here, we aimed to assess the mechanisms and signalling pathways in the neuroprotective effect of gastrodin, a phenolic glycoside, on murine neuroblastoma N2a cells expressing human Swedish mutant APP (N2a/APP). We found that gastrodin increased the levels of presynaptic-SNAP, synaptophysin, and postsynaptic-PSD95 and reduced phospho-tau Ser396, APP and Aß1-42 levels in N2a/APP cells. Gastrodin treatment reduced reactive oxygen species generation, lipid peroxidation, mitochondrial fragmentation and DNA oxidation; restored mitochondrial membrane potential and intracellular ATP production. Upregulated phospho-GSK-3ß and reduced phospho-ERK and phospho-JNK were involved in the protective effect of gastrodin. In conclusion, we demonstrated the neuroprotective effect of gastrodin in the N2a/APP cell line by ameliorating the impairment on synaptic and mitochondrial function, reducing tau phosphorylation, Aß1-42 levels as well as reactive oxygen species generation. These results provide new mechanistic insights into the potential effect of gastrodin in the treatment of Alzheimer's disease.