Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2.

Essential for reactive oxygen species (EROS) protein is a recently identified molecular chaperone of NOX2 (gp91phox), the catalytic subunit of phagocyte NADPH oxidase. Deficiency in EROS is a recently identified cause for chronic granulomatous disease, a genetic disorder with recurrent bacterial and fungal infections. Here, we report a cryo-EM structure of the EROS-NOX2-p22phox heterotrimeric complex at an overall resolution of 3.56Å. EROS and p22phox are situated on the opposite sides of NOX2, and there is no direct contact between them. EROS associates with NOX2 through two antiparallel transmembrane (TM) α-helices and multiple ß-strands that form hydrogen bonds with the cytoplasmic domain of NOX2. EROS binding induces a 79° upward bend of TM2 and a 48° backward rotation of the lower part of TM6 in NOX2, resulting in an increase in the distance between the two hemes and a shift of the binding site for flavin adenine dinucleotide (FAD). These conformational changes are expected to compromise superoxide production by NOX2, suggesting that the EROS-bound NOX2 is in a protected state against activation. Phorbol myristate acetate, an activator of NOX2 in vitro, is able to induce dissociation of NOX2 from EROS with concurrent increase in FAD binding and superoxide production in a transfected COS-7 model. In differentiated neutrophil-like HL-60, the majority of NOX2 on the cell surface is dissociated with EROS. Further studies are required to delineate how EROS dissociates from NOX2 during its transport to cell surface, which may be a potential mechanism for regulation of NOX2 activation.

Can touchscreens replace teachers? Chinese children's character learning from a touchscreen-based app, video, or face-to-face instruction.

Given the increasing prevalence of touchscreen devices that are intended for educational purposes, this study explored children's transfer of learning from touchscreen media compared with video and offline face-to-face learning. A total of 76 5- and 6-year-old Chinese kindergarten children (M = 68.21 months, SD = 3.57, range = 62-76; 30 boys and 46 girls) were randomly assigned to learn eight Chinese characters using a touchscreen-based app, using a video, or through face-to-face interaction. Learning was measured via the recall task scores, recognition task scores, recall efficiency, and recognition efficiency. The results revealed that children's recall and recognition task scores improved when learning took place using the touchscreen or face-to-face interaction. Children's recall efficiency and recognition efficiency were strongest in the face-to-face condition, followed by the touchscreen condition and then the video condition. The effects of instructional format on children's recall and recognition scores and recall efficiency were moderated by age; younger children's recall and recognition scores in the face-to-face condition and the touchscreen condition were significantly higher than in the video condition, yet older children's recall and recognition scores did not differ between conditions. However, for recall efficiency, younger children's recall efficiency in the face-to-face condition and the touchscreen condition was significantly higher than in the video condition; older children's recall efficiency in the face-to-face condition was higher than in both the touchscreen condition and the video condition. In conclusion, both face-to-face interaction and a touchscreen-based app were helpful ways for children to learn Chinese characters compared with video, but face-to-face learning showed advantages over touchscreen learning in recall efficiency for older children.

Dragging but not tapping promotes preschoolers' numerical estimating with touchscreens.

When solving mathematical problems, young children will perform better when they can use gestures that match mental representations. However, despite their increasing prevalence in educational settings, few studies have explored this effect in touchscreen-based interactions. Thus, we investigated the impact on young children's performance of dragging (where a continuous gesture is performed that is congruent with the change in number) and tapping (involving a discrete gesture that is incongruent) on a touchscreen device when engaged in a continuous number line estimation task. By examining differences in the set size and position of the number line estimation, we were also able to explore the boundary conditions for the superiority effect of congruent gestures. We used a 2 (Gesture Type: drag or tap) × 2 (Set Size: Set 0-10 or Set 0-20) × 2 (Position: left of midpoint or right of midpoint) mixed design. A total of 70 children aged 5 and 6 years (33 girls) were recruited and randomly assigned to either the Drag or Tap group. We found that the congruent gesture (drag) generally facilitated better performance with the touchscreen but with boundary conditions. When completing difficult estimations (right side in the large set size), the Drag group was more accurate, responded to the stimulus faster, and spent more time manipulating than the Tap group. These findings suggest that when children require explicit scaffolding, congruent touchscreen gestures help to release mental resources for strategic adjustments, decrease the difficulty of numerical estimation, and support constructing mental representations.

Exploring factors influencing young children's learning from storybooks: Interactive and multimedia features.

Electronic storybooks are increasingly popular with preschoolers. The purpose of our research was to investigate the effects of interactive and multimedia features in electronic storybooks on preschoolers' learning. We assigned 4- to 6-year-old children to different reading conditions in two experiments. Children were required to complete tests for learning outcomes and answer questions about the reading experience. In Experiment 1, children in the interactive (self-paced) group needed to turn the pages by a button on the page, whereas the pages were turned automatically in the non-interactive (system-controlled) group. We found that children in the system-controlled condition performed better in inference making than children in the self-paced condition. In Experiment 2, we used a 2 (Animation: present or non-present) × 2 (Background Music: present or non-present) between-participants design. We found that children's scores of learning and interest in groups with animations were higher than those in groups without animations. This research suggests that electronic books with animations congruent with the learning content promote learning for both adults and young children. Thus, we offer suggestions for designers of electronic books. Moreover, the study provides implications for educators and parents, and we suggest that multi-featured electronic storybooks for preschoolers should be carefully selected.

Reciprocal regulation between nicotinamide adenine dinucleotide metabolism and abscisic acid and stress response pathways in Arabidopsis.

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme that has emerged as a central hub linking redox equilibrium and signal transduction in living organisms. The homeostasis of NAD is required for plant growth, development, and adaption to environmental cues. In this study, we isolated a chilling hypersensitive Arabidopsis thaliana mutant named qs-2 and identified the causal mutation in the gene encoding quinolinate synthase (QS) critical for NAD biosynthesis. The qs-2 mutant is also hypersensitive to salt stress and abscisic acid (ABA) but resistant to drought stress. The qs-2 mutant accumulates a reduced level of NAD and over-accumulates reactive oxygen species (ROS). The ABA-hypersensitivity of qs-2 can be rescued by supplementation of NAD precursors and by mutations in the ABA signaling components SnRK2s or RBOHF. Furthermore, ABA-induced over-accumulation of ROS in the qs-2 mutant is dependent on the SnRK2s and RBOHF. The expression of QS gene is repressed directly by ABI4, a transcription factor in the ABA response pathway. Together, our findings reveal an unexpected interplay between NAD biosynthesis and ABA and stress signaling, which is critical for our understanding of the regulation of plant growth and stress responses.

Protective effects of natural compounds against oxidative stress in ischemic diseases and cancers via activating the Nrf2 signaling pathway: A mini review.

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been seen in the pathological states of many disorders such as ischemic diseases and cancers. Many natural compounds (NCs) have long been recognized to ameliorate oxidative stress due to their inherent antioxidant activities. The modulation of oxidative stress by NCs via activating the Nrf2 signaling pathway is summarized in the review. Three NCs, ursolic acid, betulinic acid, and curcumin, and the mechanisms of their cytoprotective effects are investigated in myocardial ischemia, cerebral ischemia, skin cancer, and prostate cancer. To promote the therapeutic performance of NCs with poor water solubility, the formulation approach, such as the nano drug delivery system, is elaborated as well in this review.

Unsafe to eat? How familiar cartoon characters affect children's learning about potentially harmful foods.

Young children learn about the properties of foods, such as taste and healthiness, from others. By using selective trust tasks in which a familiar cartoon character and an unfamiliar informant provided different testimony about food safety, this study examined how an informant's familiarity affected 4- to 6-year-old children's selective social learning about food safety. In Experiment 1, when judging the safety of foods from the familiar cartoon character and the unfamiliar character, children across all age groups showed a preference for asking the familiar character for information. For endorse questions, 4- and 5-year-olds did not consistently accept or reject either character's statements, while 6-year-olds endorsed the unfamiliar cartoon character's statements more often than the familiar character's statements. In Experiment 2, when the unfamiliar informant was a real adult instead of a fictional cartoon character, children sought out information from the familiar character more often than from the adult, and they did not differentially endorse statements by either informant. Moreover, children who had less advanced theory of mind skills and who viewed cartoon characters as more real were more likely to ask the cartoon character. These results suggest that although children prefer to obtain information from familiar characters, they accept information about food safety from multiple kinds of sources and their social-cognitive skills play a role in their decisions.

The role of epistemic and social characteristics in children's selective trust: Three meta-analyses.

Over the last 15 years, researchers have been increasingly interested in understanding the nature and development of children's selective trust. Three meta-analyses were conducted on a total of 51 unique studies (88 experiments) to provide a quantitative overview of 3- to 6-year-old children's selective trust in an informant based on the informant's epistemic or social characteristics, and to examine the relation between age and children's selective trust decisions. The first and second meta-analyses found that children displayed medium-to-large pooled effects in favor of trusting the informant who was knowledgeable or the informant with positive social characteristics. Moderator analyses revealed that 4-year-olds were more likely to endorse knowledgeable informants than 3-year-olds. The third meta-analysis examined cases where two informants simultaneously differed in their epistemic and social characteristics. The results revealed that 3-year-old children did not selectively endorse informants who were more knowledgeable but had negative social characteristics over informants who were less knowledgeable but had positive social characteristics. However, 4- to 6-year-olds consistently prioritized epistemic cues over social characteristics when deciding who to trust. Together, these meta-analyses suggest that epistemic and social characteristics are both valuable to children when they evaluate the reliability of informants. Moreover, with age, children place greater value on epistemic characteristics when deciding whether to endorse an informant's testimony. Implications for the development of epistemic trust and the design of studies of children's selective trust are discussed.

Two Chloroplast Proteins Suppress Drought Resistance by Affecting ROS Production in Guard Cells.

Chloroplast as the site for photosynthesis is an essential organelle in plants, but little is known about its role in stomatal regulation and drought resistance. In this study, we show that two chloroplastic proteins essential for thylakoid formation negatively regulate drought resistance in Arabidopsis (Arabidopsis thaliana). By screening a mutant pool with T-DNA insertions in nuclear genes encoding chloroplastic proteins, we identified an HCF106 knockdown mutant exhibiting increased resistance to drought stress. The hcf106 mutant displayed elevated levels of reactive oxygen species (ROS) in guard cells, improved stomatal closure, and reduced water loss under drought conditions. The HCF106 protein was found to physically interact with THF1, a previously identified chloroplastic protein crucial for thylakoid formation. The thf1 mutant phenotypically resembled the hcf106 mutant and displayed more ROS accumulation in guard cells, increased stomatal closure, reduced water loss, and drought resistant phenotypes compared to the wild type. The hcf106thf1 double mutant behaved similarly as the thf1 single mutant. These results suggest that HCF106 and THF1 form a complex to modulate chloroplast function and that the complex is important for ROS production in guard cells and stomatal control in response to environmental stresses. Our results also suggest that modulating chloroplastic proteins could be a way for improving drought resistance in crops.

[Determination of polysaccharides content of Gentiana farreri from different producing areas based on anthrone-sulfuric acid method].

Study a method for the detemination of the content of polysaccharides in Gentiana farreri, and analysis of the content of polysaccharides from different producing areas. The results showed that using the anthrone-sulfuric acid method, simple operation, accurate result. Sample was measured at 620 nm absorbance after anthrone-sulfuric acid color, at this wavelength, solution absorption and glucose showed a good linear relationship; The linearity was in the range of 0.01-0.07 g x L(-1) (r = 0.996 7). The recovery rate was 99.41%, with RSD of 2.0%. Considering the experimental conditions, to determine the solid-liquid ratio 1:60, extracting time 50 min, concentration of ethanol 80%. The mass fraction of polysaccharides was the highest to reached 0.743% in G. farreri from Gansu Xiahe. This experiment has laid a good foundation for further study on G. farreri.

Increasing the realism of on-screen embodied instructors creates more looking but less learning.

BACKGROUND: Although adding embodied instructors on the screen is considered an effective way to improve online multimedia learning, its effectiveness is still controversial. The level of realism of embodied on-screen instructors may be an influencing factor, but it is unclear how it affects multimedia learning. AIMS: We explored whether and how embodied on-screen instructors rendered with different levels of realism in multimedia lessons affect learning process and learning outcomes. SAMPLES: We recruited 125 college students as participants. METHODS: Students learned about neural transmission in an online multimedia lesson that included a real human, cartoon human, cartoon animal or no instructor. RESULTS: Students learning with cartoon human or cartoon animal instructors tended to fixate more on the relevant portions of the screen and performed better on retention and transfer tests than no instructor group. The real human group fixated more on the instructor, fixated less on the relevant portion of the screen and performed worse on a retention test in comparison to the cartoon human group. Fixation time on the instructor fully mediated the relationship between instructor realism and retention score. CONCLUSIONS: The addition of embodied on-screen instructors can promote multimedia learning, but the promotion effect would be better if the embodied instructor was a cartoon animal or cartoon human rather than a real human. This suggests an important boundary condition in which less realism of on-screen embodied instructors produces better learning processes and outcomes.

Phage-antibiotic synergy suppresses resistance emergence of Klebsiella pneumoniae by altering the evolutionary fitness.

Phage-antibiotic synergy (PAS) represents a superior treatment strategy for pathogen infections with less probability of resistance development. Here, we aim to understand the molecular mechanism by which PAS suppresses resistance in terms of population evolution. A novel hypervirulent Klebsiella pneumoniae (KP) phage H5 was genetically and structurally characterized. The combination of H5 and ceftazidime (CAZ) showed a robust synergistic effect in suppressing resistance emergence. Single-cell Raman analysis showed that the phage-CAZ combination suppressed bacterial metabolic activities, contrasting with the upregulation observed with phage alone. The altered population evolutionary trajectory was found to be responsible for the contrasting metabolic activities under different selective pressures, resulting in pleiotropic effects. A pre-existing wcaJ point mutation (wcaJG949A) was exclusively selected by H5, conferring a fitness advantage and up-regulated activity of carbohydrate metabolism, but also causing a trade-off between phage resistance and collateral sensitivity to CAZ. The wcaJ point mutation was counter-selected by H5-CAZ, inducing various mutations in galU that imposed evolutionary disadvantages with higher fitness costs, and suppressed carbohydrate metabolic activity. H5 and H5-CAZ treatments resulted in opposite effects on the transcriptional activity of the phosphotransferase system and the ascorbate and aldarate metabolism pathway, suggesting potential targets for phage resistance suppression. Our study reveals a novel mechanism of resistance suppression by PAS, highlighting how the complexity of bacterial adaptation to selective pressures drives treatment outcomes. IMPORTANCE: Phage-antibiotic synergy (PAS) has been recently proposed as a superior strategy for the treatment of multidrug-resistant pathogens to effectively reduce bacterial load and slow down both phage and antibiotic resistance. However, the underlying mechanisms of resistance suppression by PAS have been poorly and rarely been studied. In this study, we tried to understand how PAS suppresses the emergence of resistance using a hypervirulent Klebsiella pneumoniae (KP) strain and a novel phage H5 in combination with ceftazidime (CAZ) as a model. Our study reveals a novel mechanism by which PAS drives altered evolutionary trajectory of bacterial populations, leading to suppressed emergence of resistance. The findings advance our understanding of how PAS suppresses the emergence of resistance, and are imperative for optimizing the efficacy of phage-antibiotic therapy to further improve clinical outcomes.

The ATP-bound inward-open conformation of ABCC4 reveals asymmetric ATP binding for substrate transport.

The multidrug resistance-associated protein (MRP) ABCC4 facilitates substrate transport across the cytoplasmic membrane, crucial for normal physiology and mediating multidrug resistance in tumor cells. Despite intensive studies on MRPs, ABCC4's transport mechanism remains incompletely understood. In this study, we unveiled an inward-open conformation with an ATP bound to degenerate NBD1. Additionally, we captured the structure with both ATP and substrate co-bound in the inward-open state. Our findings uncover the asymmetric ATP binding in ABCC4 and provide insights into substrate binding and transport mechanisms. ATP binding to NBD1 is parallel to substrate binding to ABCC4, and is a prerequisite for ATP-bound NBD2-induced global conformational changes. Our findings shed new light on targeting ABCC4 in combination with anticancer therapy.

When the internet is wrong: Children's trust in an inaccurate internet or human source.

Prior studies have shown that children can select and evaluate information based on the previous accuracy of an informant. The current study examines how 5- to 6-year-old kindergarteners (N = 46) and 7- to 8-year-old second-graders (N = 48) in China judge scientific information provided by the internet or a teacher, and how a source's history of inaccuracy influences participants' judgments. When lacking explicit information about previous accuracy, neither younger children nor older children showed differential trust in the internet or a teacher. After observing the internet providing inaccurate information, children in both age groups decreased their trust in statements from the internet. When the teacher was consistently inaccurate, children in both age groups also showed reduced preference for the teacher's statements. These findings demonstrate that 5- to 8-year-old children take into account history of inaccuracy when deciding whether to request or endorse information from the internet or a teacher.

Meta-Analysis of Low Temperature Plasma Radiofrequency Ablation and CO2 Laser Surgery on Early Glottic Laryngeal Carcinoma.

Objective: Meta-analysis is used to analyze the treatment of early glottic laryngeal carcinoma by cryogenic plasma radiofrequency ablation combined with CO2 laser surgery. Methods: Retrieval of PubMed, Embase, Medline, VIP, Wanfang, and CNKI databases using a computer. The retrieval period is from the creation of the database until August 31, 2021. References to the included literature were also searched at the same time. According to the inclusion and exclusion criteria, literatures are screened independently, relevant data were extracted, and meta-analysis was conducted. Results: Recurrence rates are reported in seven literatures. In interstudy heterogeneity test: P = 0.624, I 2 = 0%, fixed effect model analysis shows that there is no significant difference in recurrence rate between low temperature plasma radiofrequency ablation and CO2 laser ablation (OR = 0.80, 95% CI (0.35, 1.29), P = 0.371). Intraoperative blood loss is reported in 5 literatures, and heterogeneity test of each study is as follows: P = 0.03, I 2 = 67%. Low temperature plasma radiofrequency ablation results in more intraoperative blood loss than CO2 laser ablation (SMD = -0.71, 95% CI (0.08, 0.82), P = 0.01). There are five reports on postoperative pain in two treatments: P = 0.04, I 2 = 64%. There is no significant difference in postoperative pain between low temperature plasma radiofrequency ablation and CO2 laser ablation (SMD = -0.21, 95% CI (-0.44, 0.10), P = 0.134). Operative time is reported in nine articles: P < 0.01, I 2 = 95%. The operative time of low temperature plasma radiofrequency ablation is significantly shorter than CO2 laser ablation (SMD = -2.38, 95% CI (-3.91, -1.62), P < 0.01). There are two reports on postoperative mucosal recovery: P = 0.328, I 2 = 2%. Low temperature plasma radiofrequency ablation was significantly better than CO2 laser ablation in postoperative mucosal recovery (OR = 5.49, 95% CI (2.36, 10.18), P < 0.01). Conclusion: Low temperature plasma radiofrequency ablation is superior to CO2 laser surgery in the treatment of early glottic laryngeal carcinoma in terms of operative time and postoperative mucosal recovery. Low-temperature plasma radiofrequency ablation, on the other hand, results in higher intraoperative blood loss, with no discernible difference in recurrence rate or postoperative pain severity between the two treatments.

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils.

The hippocampal neurogenesis occurs constitutively throughout adulthood in mammalian species, but declines with age. In this study, we overtly found that the neuroblast proliferation and differentiation in the subgranular zone and the maturation into fully functional and integrated neurons in the granule-cell layer in young gerbils following cerebral ischemia/reperfusion was much more than those in old gerbils. The neurological function and cognitive and memory-function rehabilitation in the young gerbils improved faster than those in the old one. These results demonstrated that, during long term after cerebral ischemia/reperfusion, the ability of neurogenesis and recovery of nerve function in young animals were significantly higher than that in the old animals. We found that, after 14- and 28-day cerebral ischemia/reperfusion, the phosphorylation of MEK1/2, ERK1/2, p90RSK, and MSK1/2 protein levels in the hippocampus of young gerbils was significantly much higher than that of old gerbils. The levels of autophagy-related proteins, including Beclin-1, Atg3, Atg5, and LC3 in the hippocampus were effectively maintained and elevated at 28 days after cerebral ischemia/reperfusion in the young gerbils compared with those in the old gerbils. These results indicated that an increase or maintenance of the phosphorylation of ERK1/2 signal pathway and autophagy-related proteins was closely associated with the neuroblast proliferation and differentiation and the process of maturation into neurons. Further, we proved that neuroblast proliferation and differentiation in the dentate gyrus and cognitive function were significantly reversed in young cerebral ischemic gerbils by administering the ERK inhibitor (U0126) and autophagy inhibitor (3MA). In brief, following experimental young ischemic stroke, the long-term promotion of the neurogenesis in the young gerbil's hippocampal dentate gyrus by upregulating the phosphorylation of ERK signaling pathway and maintaining autophagy-related protein levels, it overtly improved the neurological function and cognitive and memory function.

Protective Effects of Iridoid Glycoside from Corni Fructus on Type 2 Diabetes with Nonalcoholic Fatty Liver in Mice.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Accumulating evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) shares common typical features with T2DM, and they affect each other extensively. Thus, NAFLD has emerged as a novel target for T2DM prevention and care. Although Corni Fructus (CF) and its extracts have a therapeutic effect on T2DM, its effects and mechanisms on T2DM with NAFLD are far from elucidated. In this study, a mouse model of T2DM with NAFLD complication was established in ICR mice by feeding a high-fat, high-sugar (HFHS) diet and intraperitoneally injecting with a low dose of streptozotocin (STZ). Then, the effects of iridoid glycosides (IG) extracted from CF on this mouse model were investigated. We found that 4-week IG administration remarkably alleviated hyperglycemia and insulin resistance and significantly reduced inflammation, oxidative stress, and fat accumulation in the liver of T2DM with NAFLD mice. Further studies showed that IG inhibited the NF-κB but enhanced the PI3K-AKT signaling pathway. In summary, these results indicated that the IG from CF has potential therapeutic effects on T2DM with NAFLD.

A network-based method for mechanistic investigation and neuroprotective effect on treatment of tanshinone â against ischemic stroke in mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanshinone-Ⅰ (TSNⅠ), a member of the mainly active components of Salvia miltiorrhiza Bunge (Dan Shen), which is widely used for the treatment for modern clinical diseases including cardiovascular and cerebrovascular diseases, has been reported to show the properties of anti-oxidation, anti-inflammation, neuroprotection and other pharmacological actions. However, whether TSNⅠ can improve neuron survival and neurological function against transient focal cerebral ischemia (tMCAO) in mice is still a blank field. AIM OF THE STUDY: This study aims to investigate the neuroprotective effects of TSNⅠ on ischemic stroke (IS) induced by tMCAO in mice and explore the potential mechanism of TSNⅠ against IS by combining network pharmacology approach and experimental verification. MATERIALS AND METHODS: In this study, the pivotal candidate targets of TSNⅠ against IS were screened by network pharmacology firstly. Enrichment analysis and molecular docking of those targets were performed to identify the possible mechanism of TSNⅠ against IS. Afterwards, experiments were carried out to further verify the mechanism of TSNⅠ against IS. The infarct volume and neurological deficit were evaluated by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and Longa respectively. Immunohistochemistry was used to observe neuronal death in the hippocampus and cortical regions by detecting the change of NeuN. The predicting pathways of signaling-related proteins were assessed by Western blot in vitro and in vivo experiments. RESULTS: In vivo, TSNⅠ was found to dose-dependently decrease mice's cerebral infarct volume induced by tMCAO. In vitro, pretreatment with TSNⅠ could increase cell viability of HT-22 cell following oxygen-glucose deprivation (OGD/R). Moreover, the results showed that 125 candidate targets were identified, Protein kinase B (AKT) signaling pathway was significantly enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and mitogen-activated protein kinases 1 (MAPK1) and AKT1 could be bound to TSNⅠ more firmly by molecular docking analysis, which implies that TSNⅠ may play a role in neuroprotection through activating AKT and MAPK signaling pathways. Meanwhile, TSNⅠ was confirmed to significantly protect neurons from injury induced by IS through activating AKT and MAPK signaling pathways. CONCLUSION: In conclusion, our study clarifies that the mechanism of TSNⅠ against IS might be related to AKT and MAPK signaling pathways, which may provide the basic evidence for further development and utilization of TSNⅠ.