Computational identification of mitochondrial dysfunction biomarkers in severe SARS-CoV-2 infection: Facilitating therapeutic applications of phytomedicine.

BACKGROUND: Currently, SARS-CoV-2 has not disappeared and continues to prevail worldwide, with the ongoing risk of mutations and the potential for severe COVID-19. The impairment of monocyte mitochondrial function caused by SARS-CoV-2, leading to a metabolic and immune dysregulation, is a crucial factor in the development of severe COVID-19. PURPOSE: Discover effective phytomedicines based on mitochondrial-related biomarkers in severe SARS-CoV-2 infection. METHODS: Firstly, differential gene analysis and gene set enrichment analysis (GSEA) were conducted on monocytes datasets to identify genes and pathways distinguishing severe patients from uninfected individuals. Then, GO and KEGG enrichment analysis on the differentially expressed genes (DEGs) obtained. Take the DEGs and intersect them with the MitoCarta 3.0 gene set to obtain the differentially expressed mitochondrial-related genes (DE-MRGs). Subsequently, machine learning algorithms were employed to screen potential mitochondrial dysfunction biomarkers for severe COVID-19 based on score values. ROC curves were then plotted to assess the distinguish capability of the biomarkers, followed by validation using two additional independent datasets. Next, the effects of the identified biomarkers on metabolic pathways and immune cells were explored through Gene Set Variation Analysis (GSVA) and CIBERSORT. Finally, potential nature products for severe COVID-19 were screened from the expression profile dataset based on dysregulated mitochondrial-related genes, followed by in vitro experimental validation. RESULTS: There are 1812 DEGs and 17 dysregulated mitochondrial processes between severe COVID-19 patients and uninfected individuals. A total of 77 DE-MRGs were identified, and the potential biomarkers were identified as RECQL4, PYCR1, PIF1, POLQ, and GLDC. In both the training and validation sets, the area under the ROC curve (AUC) for these five biomarkers was greater than 0.9. And they did not show significant changes in mild to moderate patients (p > 0.05), indicating their ability to effectively distinguish severe COVID-19. These biomarkers exhibit a highly significant correlation with the dysregulated metabolic processes (p < 0.05) and immune cell imbalance (p < 0.05) in severe patients, as demonstrated by GSVA and CIBERSORT algorithms. Curcumin has the highest score in the predictive model based on transcriptomic data from 496 natural compounds (p = 0.02; ES = 0.90). Pre-treatment with curcumin for 8 h has been shown to alleviate mitochondrial membrane potential damage caused by the SARS-CoV-2 S1 protein (p < 0.05) and reduce elevated levels of reactive oxygen species (ROS) (p < 0.01). CONCLUSION: The results of this study indicate a significant correlation between severe SARS-CoV-2 infection and mitochondrial dysfunction. The proposed mitochondrial dysfunction biomarkers identified in this study are associated with the disease progression, metabolic and immune changes in severe SARS-CoV-2 infected patients. Curcumin has a potential role in preventing severe COVID-19 by protecting mitochondrial function. Our findings provide new strategies for predicting the prognosis and enabling early intervention in SARS-CoV-2 infection.

Impact of molecular weight and gastrointestinal digestion on the immunomodulatory effects of Lycium barbarum polysaccharides.

In traditional Chinese medicine, Lycium barbarum is of rich medicinal value, and its polysaccharides are particularly interesting due to their significant pharmacological effects and potential health benefits. This study investigated the immunomodulatory effects of Lycium barbarum polysaccharides (LBPs) by examining their interaction with the TLR4/MD-2 complex and the impacts of gastrointestinal digestion on these interactions. We discovered that the affinity binding of LBPs for TLR4/MD-2 and their cytokine induction capability are influenced by molecular weight, with medium-sized LBPs (100-300 kDa) exhibiting stronger binding affinity and induction capability. Conversely, LBPs smaller than 10 kDa showed reduced activity. Additionally, the content of arabinose and galactose within the LBPs fractions was found to correlate positively with both receptor affinity and cytokine secretion. Simulated gastrointestinal digestion resulted in the degradation of LBPs into smaller fragments that are rich in glucose. Although these fragments exhibited decreased binding affinity to the TLR4/MD-2 complex, they maintained their activity to promote cytokine production. Our findings highlight the significance of molecular weight and specific monosaccharide composition in the immunomodulatory function of LBPs and emphasize the influence of gastrointestinal digestion on the effects of LBPs. This research contributes to a better understanding of the mechanisms underlying the immunomodulatory effects of traditional Chinese medicine polysaccharides and their practical application.

Tumor vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Suppresses macrophage capping protein beyond STING activation.

The vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) induces apoptosis in vascular endothelial cells and leads to tumor hemorrhagic necrosis. While DMXAA has been proven to be a potent agonist of murine stimulator of interferon genes (mSTING), it has little effect on human-STING (hSTING). This species selectivity of DMXAA may explain its effectiveness against solid tumors in mice and its failure in clinical trials. However, DMXAA did reduce tumor volume in some patients during clinical trials. These paradoxical results have prompted us to investigate the anti-tumor mechanism of DMXAA beyond STING in the destruction of tumor vasculature in humans. In this study, we demonstrated that DMXAA binds to both human and mouse macrophage capping protein (CapG), with a KD of 5.839 µM for hCapG and a KD of 2.867 µM for mCapG, as determined by surface plasmon resonance (SPR) analysis. Homology modeling and molecular docking analysis of hCapG indicated that the critical residues involved in the hydrogen bond interaction of DMXAA with hCapG were Arg153, Thr151, and GLN141, Asn234. In addition, electrostatic pi-cation interaction occurred between DMXAA and hCapG. Further functional studies revealed that CapG protein plays a crucial role in the effects of DMXAA on human umbilical endothelial vein cell (HUEVC) angiogenesis and migration, as well as the expression of cytoskeletal proteins actin and tubulin, and the invasion of A549 lung adenocarcinoma cells. Our study has originally uncovered a novel cross-species pathway underlying the antitumor vascular disruption of DMXAA extends beyond STING activation. This finding deepens our understanding of the multifaceted actions of flavonoid VDAs in animal models and in clinical settings, and may provide insights for the precise therapy of DMXAA based on the biomarker CapG protein.

Inhibition of multiple SARS-CoV-2 variants entry by Lycium barbarum L. polysaccharides through disruption of spike protein-ACE2 interaction.

Viral respiratory infections are major human health concerns. The most striking epidemic disease, COVID-19 is still on going with the emergence of fast mutations and drug resistance of pathogens. A few polysaccharide macromolecules from traditional Chinese medicine (TCM) have been found to have direct anti-SARS-CoV-2 activity but the mechanism remains unclear. In this study, we evaluated the entry inhibition effect of Lycium barbarum polysaccharides (LBP) in vitro and in vivo. We found LBP effectively suppressed multiple SARS-CoV-2 variants entry and protected K18-hACE2 mice from invasion with Omicron pseudovirus (PsV). Moreover, we found LBP interfered with early entry events during infection in time-of-addition (TOA) assay and SEM observation. Further surface plasmon resonance (SPR) study revealed the dual binding of LBP with Spike protein and ACE2, which resulted in the disruption of Spike-ACE2 interaction and subsequently triggered membrane fusion. Therefore, LBP may act as broad-spectrum inhibitors of virus entry and nasal mucosal protective agent against newly emerging respiratory viruses, especially SARS-CoV-2.

PC3T: a signature-driven predictor of chemical compounds for cellular transition.

Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tunable approach to overcome these issues. Here, we present PC3T, a computational framework to enrich molecules that induce desired cellular transitions, and PC3T was able to consistently enrich small molecules that had been experimentally validated in both bulk and single-cell datasets. We then predicted small molecule reprogramming of fibroblasts into hepatic progenitor-like cells (HPLCs). The converted cells exhibited epithelial cell-like morphology and HPLC-like gene expression pattern. Hepatic functions were also observed, such as glycogen storage and lipid accumulation. Finally, we collected and manually curated a cell state transition resource containing 224 time-course gene expression datasets and 153 cell types. Our framework, together with the data resource, is freely available at http://pc3t.idrug.net.cn/ . We believe that PC3T is a powerful tool to promote chemical-induced cell state transitions.

Various Energetic Metabolism of Microglia in Response to Different Stimulations.

The activation of the microglia plays an important role in the neuroinflammation induced by different stimulations associated with Alzheimer's disease (AD). Different stimulations, such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) and cytokines, trigger a consequence of activation in the microglia with diverse changes of the microglial cell type response in AD. The activation of the microglia is often accompanied by metabolic changes in response to PAMPs, DAMPs and cytokines in AD. Actually, we do not know the distinct differences on the energetic metabolism of microglia when subject to these stimuli. This research assessed the changes of the cell type response and energetic metabolism in mouse-derived immortalized cells (BV-2 cells) induced by a PAMP (LPS), DAMPs (Aß and ATP) and a cytokine (IL-4) in mouse-derived immortalized cells (BV-2 cells) and whether the microglial cell type response was improved by targeting the metabolism. We uncovered that LPS, a proinflammatory stimulation of PAMPs, modified the morphology from irregular to fusiform, with stronger cell viability, fusion rates and phagocytosis in the microglia accompanied by a metabolic shift to the promotion of glycolysis and the inhibition of oxidative phosphorylation (OXPHOS). Aß and ATP, which are two known kinds of DAMPs that trigger microglial sterile activation, induced the morphology from irregular to amoebic, and significantly decreased others in the microglia, accompanied by boosting or reducing both glycolysis and OXPHOS. Monotonous pathological changes and energetic metabolism of microglia were observed under IL-4 exposure. Further, the inhibition of glycolysis transformed the LPS-induced proinflammatory morphology and decreased the enhancement of LPS-induced cell viability, the fusion rate and phagocytosis. However, the promotion of glycolysis exerted a minimal effect on the changes of morphology, the fusion rate, cell viability and phagocytosis induced by ATP. Our study reveals that microglia induced diverse pathological changes accompanied by various changes in the energetic metabolism in response to PAMPs, DAMPs and cytokines, and it may be a potential application of targeting the cellular metabolism to interfere with the microglia-mediated pathological changes in AD.

What can traditional Chinese medicine do for adult neurogenesis?

Adult neurogenesis plays a crucial role in cognitive function and mood regulation, while aberrant adult neurogenesis contributes to various neurological and psychiatric diseases. With a better understanding of the significance of adult neurogenesis, the demand for improving adult neurogenesis is increasing. More and more research has shown that traditional Chinese medicine (TCM), including TCM prescriptions (TCMPs), Chinese herbal medicine, and bioactive components, has unique advantages in treating neurological and psychiatric diseases by regulating adult neurogenesis at various stages, including proliferation, differentiation, and maturation. In this review, we summarize the progress of TCM in improving adult neurogenesis and the key possible mechanisms by which TCM may benefit it. Finally, we suggest the possible strategies of TCM to improve adult neurogenesis in the treatment of neuropsychiatric disorders.

Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification.

A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-ß-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress.

Deletion of AhR attenuates fear memory leaving other types of memory intact.

The aryl hydrocarbon receptor (AhR), a classic "environmental sensor", has been found to play an important role in cognitive and emotional function. Recent studies showed AhR deletion led to an attenuated fear memory, providing a potential target against fear memory, whether it is the consequence of attenuated sense of fear or memory ability deficit or both is unclear. Here this study aims to work this out. The freezing time in contextual fear conditioning (CFC) reduced significantly in AhR knockout mice, indicating an attenuated fear memory. Hot plate test and acoustic startle reflex showed that AhR knockout did not change the pain threshold and hearing, excluded the possibility of sensory impairments. Results from NORT, MWM and SBT showed that deletion of AhR had little effects on other types of memory. But the anxiety-like behaviors reduced both in naïve or suffered (tested after CFC) AhR knockout mice, showing that AhR-deficient mice have a reduced basal and stressful emotional response. The basal low-frequency to high-frequency (LF/HF) ratio of the AhR knockout mice was significantly lower than that of the control group, indicating lower sympathetic excitability in the basal state, suggesting a low level of basal stress in the knockout mice. Before and after CFC, the LF/HF ratio of AhR-KO mice tended to be significantly lower than that of WT mice, and their heart rate was significantly lower; and the AhR-KO mice also has a decreased serum corticosterone level after CFC, suggesting a reduced stress response in AhR knockout mice. Altogether, the basal stress level and stress response were significant reduced in AhR knockout mice, which might contribute to the attenuated fear memory with little impairment on other types of memory, suggesting AhR as a "psychologic sensor" additional to "environmental sensor".

Influence of gut microbiota on resilience and its possible mechanisms.

Excessive stress leads to disruptions of the central nervous system. Individuals' responses to stress and trauma differ from person to person. Some may develop various neuropsychiatric disorders, such as post-traumatic stress disorder, major depression, and anxiety disorders, while others may successfully adapt to the same stressful events. These two neural phenotypes are called susceptibility and resilience. Previous studies have suggested resilience/susceptibility as a complex, non-specific systemic response involving central and peripheral systems. Emerging research of mechanisms underlying resilience is mostly focussing on the physiological adaptation of specific brain circuits, neurovascular impairment of the blood-brain barrier, the role of innate and adaptive factors of the immune system, and the dysbiosis of gut microbiota. In accordance with the microbiota-gut-brain axis hypothesis, the gut microbiome directly influences the interface between the brain and the periphery to affect neuronal function. This review explored several up-to-date studies on the role of gut microbiota implicated in stressful events-related resilience/susceptibility. We mainly focus on the changes in behavior and neuroimaging characteristics, involved brain regions and circuits, the blood-brain barrier, the immune system, and epigenetic modifications, which contribute to stress-induced resilience and susceptibility. The perspective of the gut-brain axis could help to understand the mechanisms underlying resilience and the discovery of biomarkers may lead to new research directions and therapeutic interventions for stress-induced neuropsychiatric disorders.

Stress-altering anterior insular cortex activity affects risk decision-making behavior in mice of different sexes.

Stress can affect people's judgment and make them take risky decisions. Abnormal decision-making behavior is a core symptom of psychiatric disorders, such as anxiety, depression, and substance abuse. However, the neuronal mechanisms underlying such impairments are largely unknown. The anterior insular cortex (AIC) is a crucial structure to integrate sensory information with emotional and motivational states. These properties suggest that AIC can influence a subjective prediction in decision-making. In this study, we demonstrated that stressed mice prefer to take more risky choices than control mice using a gambling test. Manipulating the neural activity of AIC or selectively inhibiting the AIC-BLA pathway with chemogenetic intervention resulted in alterations in risk decision-making in mice. Different sexes may have different decision-making strategies in risky situations. Endogenous estrogen levels affect emotional cognition by modulating the stress system function in women. We observed decision-making behavior in mice of different sexes with or without stress experience. The result showed that female mice did not change their choice strategy with increasing risk/reward probability and performed a lower risk preference than male mice after stress. Using the pharmacological method, we bilaterally injected an estrogen receptor (ER) antagonist that resulted in more risky behavior and decreased synaptic plasticity in the AIC of female mice. Our study suggested that the AIC is a crucial region involved in stress-induced alteration of decision-making, and estrogen in the AIC may regulate decision-making behavior by regulating synaptic plasticity.

Accelerating drug repurposing for COVID-19 treatment by modeling mechanisms of action using cell image features and machine learning.

The novel coronavirus disease, COVID-19, has rapidly spread worldwide. Developing methods to identify the therapeutic activity of drugs based on phenotypic data can improve the efficiency of drug development. Here, a state-of-the-art machine-learning method was used to identify drug mechanism of actions (MoAs) based on the cell image features of 1105 drugs in the  LINCS database. As the multi-dimensional features of cell images are affected by non-experimental factors, the characteristics of similar drugs vary considerably, and it is difficult to effectively identify the MoA of drugs as there is substantial noise. By applying the supervised information theoretic metric-learning (ITML) algorithm, a linear transformation made drugs with the same MoA aggregate. By clustering drugs to communities and performing enrichment analysis, we found that transferred image features were more conducive to the recognition of drug MoAs. Image features analysis showed that different features play important roles in identifying different drug functions. Drugs that significantly affect cell survival or proliferation, such as cyclin-dependent kinase inhibitors, were more likely to be enriched in communities, whereas other drugs might be decentralized. Chloroquine and clomiphene, which block the entry of virus, were clustered into the same community, indicating that similar MoA could be reflected by the cell image. Overall, the findings of the present study laid the foundation for the discovery of MoAs of new drugs, based on image data. In addition, it provided a new method of drug repurposing for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09727-5.

B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling.

The chemical warfare agent sulfur mustard (SM) causes severe cutaneous lesions characterized by epidermal cell death, apoptosis, and inflammation. At present, the molecular mechanisms underlying SM-induced injury are not well understood, and there is no standard treatment protocol for SM-exposed patients. Here, we conducted a high-content screening of the Food and Drug Administration (FDA)-approved drug library of 1018 compounds against SM injury on an immortal human keratinocyte HaCaT cell line, focusing on cell survival. We found that the B-Raf inhibitor vemurafenib had an apparent therapeutic effect on HaCaT cells and resisted SM toxicity. Other tested B-Raf inhibitors, both type-I (dabrafenib and encorafenib) and type-II (RAF265 and AZ628), also exhibited potent therapeutic effects on SM-exposed HaCaT cells. Both SM and vemurafenib triggered extracellular signal-related kinase (ERK) activation. The therapeutic effect of vemurafenib in HaCaT cells during SM injury was ERK-dependent, indicating a specific role of ERK in keratinocyte regulatory mechanisms. Furthermore, vemurafenib partially improved cutaneous damage in a mouse ear vesicant model. Collectively, our results provide evidence that the B-Raf inhibitor vemurafenib is a potential therapeutic agent against SM injury, and oncogenic B-Raf might be an exciting new therapeutic target following exposure to mustard vesicating agents.

Prognostic value of the dynamic hepatorenal function on intermediate-term mortality in TAVI patients with survival to discharge.

BACKGROUND: Renal and liver dysfunctions are risk factors for mortality in patients with severe aortic stenosis (AS). Transcatheter aortic valve implantation (TAVI) has the potential to break the vicious cycle between AS and hepatorenal dysfunction by relieving aortic valve obstruction. HYPOTHESIS: A part of patients can derive hepatorenal function improvement from TAVI, and this noncardiac benefit improves the intermediate-term outcomes. METHODS: We developed this retrospective cohort study in 439 consecutive patients undergoing TAVI and described the dynamic hepatorenal function assessed by model for end-stage liver disease model for end-stage liver disease (MELD)-XI score in subgroups. The endpoint was 2-year all-cause mortality. RESULTS: Receiver-operating characteristic analysis showed that the baseline MELD-XI score of 10.71 was the cutoff point. A high MELD-XI score (>10.71) at baseline was an independent predictor of the 2-year mortality hazard ratio (HR: 2.65 [1.29-5.47], p = .008). After TAVI, patients with irreversible high MELD-XI scores had a higher risk of 2-year mortality than patients who improved from high to low MELD-XI scores (HR: 2.50 [1.06-5.91], p = .03). Factors associated with reversible MELD-XI scores improvement were low baseline MELD-XI scores (≤12.00, odds ratio [OR]: 2.02 [1.04-3.94], p = .04), high aortic valve peak velocity (≥5 m/s, OR: 2.17 [1.11-4.24], p = .02), and low body mass index (≤25 kg/m2 , OR: 2.73 [1.25-5.98], p = .01). CONCLUSION: High MELD-XI score at baseline is an independent predictor for 2-year mortality. Patients with hepatorenal function improvement after TAVI have better outcomes. For patients with irreversible hepatorenal dysfunction after TAVI, further optimization of the subsequent treatment after TAVI is needed to improve the outcomes.

Immune index: A gene and cell prognostic signature for immunotherapy response prediction in hepatocellular carcinoma.

The heterogeneity of tumor immune microenvironment (TIME) plays important roles in the development and immunotherapy response of hepatocellular carcinoma (HCC). Using machine learning algorithms, we introduced the immune index (IMI), a prognostic model based on the HCC immune landscape. We found that IMI low HCCs were enriched in stem cell and proliferating signatures, and yielded more TP53 mutation and 17p loss compared with IMI high HCCs. More importantly, patients with high IMI exhibited better immune-checkpoint blockade (ICB) response. To facilitate clinical application, we employed machine learning algorithms to develop a gene model of the IMI (IMIG), which contained 10 genes. According to our HCC cohort examination and single-cell level analysis, we found that IMIG high HCCs exhibited favorable survival outcomes and high levels of NK and CD8+ T cells infiltration. Finally, after coculture with autologous tumor infiltrating lymphocytes, IMIG high tumor cells exhibited a better response to nivolumab treatment. Collectively, the IMI and IMIG may serve as powerful tools for the prognosis, classification and ICB treatment response prediction of HCC.

Clinical and experimental research progress on neurotoxicity of sulfur mustard and its possible mechanisms.

Sulfur mustard (SM), an extremely reactive alkylating toxicant, which poses a continuing threat to both military and civilian populations. SM targets three major organs including skin, eyes and lungs. In recent years, more and more clinical findings have shown that cognitive and emotional disorders in veterans intoxicated with SM, such as anxiety, depression, apathy, cognitive decline and so on, which indicated the long time toxic effects on mental and neurological health of SM. The experimental studies in animal and cell models have also found neurotoxicity which are similar to clinical results. However, these neuropsychological problems are not studied well in victims of SM and the mental and neurological complications are often not subjected to treatment or undertreated. Until now, the exact mechanism of the action of SM toxicity has not been elucidated and no specific therapy for its poisoning exists. Therefore, the studies on neurotoxicity of SM should be strengthened. This review summarizes the main progress of clinical and experimental researches on neurotoxicity of SM for the past few years.

A touchscreen-based paradigm to measure visual pattern separation and pattern completion in mice.

Memory accuracy involves two major processes: pattern separation and pattern completion. Pattern separation refers to the ability to reduce overlap among similar inputs to avoid interference, and pattern completion refers to the ability to retrieve the whole information from partial or degraded cues. Impairments in pattern separation/pattern completion contribute to cognitive deficits in several diseases of the nervous system. Therefore, it is better to evaluate both pattern separation and pattern completion in one apparatus. However, few tools are available to assess pattern separation and pattern completion within the same apparatus for rodents. In this study, we designed a series of images with varying degrees of similarity to the correct image to evaluate pattern separation and pattern completion. First, mice were trained to discriminate between two totally different images, and once the correct percentage reached above 77% for two consecutive days, the images with different degrees of similarity were used to measure pattern separation and pattern completion. The results showed the mice performed progressively worse from S0 to S4 (increasing similarity) when discriminating similar images in pattern separation, and the mice performed progressively worse from C0 to C4 (decreasing cues information) when recalling the correct image according to partial cues in pattern completion, implying a good image similarity-dependent manner for memory accuracy evaluation. In sum, we designed a convenient, effective paradigm to evaluate pattern separation and pattern completion based on a touchscreen pairwise discrimination task, which may provide a new method for the studies of the effects and mechanisms of memory accuracy enhancing drugs.