Biology subjects

Cui, X.

Publications and source records attributed to Cui, X..

At least 109 records · Page 6Linked to original sources

bioRxiv2023

scEpiTools: a database to comprehensively interrogate analytic tools for single-cell epigenomic data

Single-cell sequencing technology has enabled the characterization of cellular heterogeneity at an unprecedented resolution. To analyze single-cell RNA-sequencing data, numerous tools have been proposed for various analytic tasks, which have been systematically summarized and concluded in a comprehensive database called scRNA-tools. Although single-cell epigenomic data can effectively reveal the chromatin regulatory landscape that governs transcription, the analysis of single-cell epigenomic data presents assay-specific challenges, and an abundance of tools with varying types and functionalities have thus been developed. Nevertheless, these tools have not been well summarized, hindering retrieval, selection, and utilization of appropriate tools for specific analyses. To address the issues, we here proposed scEpiTools database with a multi-functional platform (http://health.tsinghua.edu.cn/scepitools). Specifically, based on the comprehensive collection and detailed annotation of 553 articles, scEpiTools groups articles into 14 major categories and 90 subcategories, provides task-specific recommendation for different emphases, and offers intuitive trend analysis via directed graphs, word clouds, and statistical distributions. For single-cell chromatin accessibility data analysis, we proposed a novel ensemble method named scEpiEnsemble, which, along with multiple methods as built-in kernels, can be used for flexible and efficient online analysis via the scEpiTools platform. We envision that scEpiTools will guide tool usage and development for single-cell epigenomic data and provide valuable resources for understanding regulatory mechanisms and cellular identity. Author summaryCompared to single-cell RNA-sequencing data, single-cell epigenomic data can reflect a set of epigenetic modifications at the cellular level. In general, the analysis of these data is typically divided into several steps: 1) retrieving available tools based on the omics of data and tasks; 2) selecting appropriate tools manually; and 3) utilizing the chosen tools to analyze data. However, due to the rapid development of tools and the unique complexity of the data, each of the above steps is extremely challenging for researchers. To provide researchers with great convenience, we developed scEpiTools (http://health.tsinghua.edu.cn/scepitools), a database with multiple functionalities. For instance, given the omics type and the analytic task, researchers can easily browse all the available tools via the hierarchical categorization of scEpiTools, and get recommendation scores from multiple perspectives. Considering that researchers may encounter difficulties in hardware requirements or environment setup, we also provide online analysis with various commonly used tools, as well as a novel ensemble method named scEpiEnsemble. In summary, scEpiTools represents a valuable resource for the single-cell epigenomics community, facilitating retrieval, selection and utilization of appropriate tools for diverse analyses, and helping to drive future advancements in the field.

bioinformatics↗

bioRxiv2023

Pathfinder: protein folding pathway prediction based on conformational sampling

The study of protein folding mechanism is a challenge in molecular biology, which is of great significance for revealing the movement rules of biological macromolecules, understanding the pathogenic mechanism of folding diseases, and designing protein engineering materials. Based on the hypothesis that the conformational sampling trajectory contain the information of folding pathway, we propose a protein folding pathway prediction algorithm named Pathfinder. Firstly, Pathfinder performs large-scale sampling of the conformational space and clusters the decoys obtained in the sampling. The heterogeneous conformations obtained by clustering are named seed states. Then, a resampling algorithm that is not constrained by the local energy basin is designed to obtain the transition probabilities of seed states. Finally, protein folding pathways are inferred from the maximum transition probabilities of seed states. The proposed Pathfinder is tested on our developed test set (34 proteins). For 5 widely studied proteins, we correctly predicted their folding pathways. For 25 partial biological experiments proteins, we predicted folding pathways could be further verified. For the other 4 proteins without biological experiment results, potential folding pathways were predicted to provide new insights into protein folding mechanism. The results reveal that structural analogs may have different folding pathways to express different biological functions, homologous proteins may contain common folding pathways, and -helices may be more prone to early protein folding than {beta}-strands.

bioinformatics↗

bioRxiv2023

Protein multiple conformations prediction using multi-objective evolution algorithm

MotivationWith the breakthrough of AlphaFold2 and the publication of AlphaFold DB, the protein structure prediction has made remarkable progress, which may further promote many potential applications of proteomics in all areas of life. However, it should be noted that AlphaFold2 models tend to represent only a single static structure, and accurately predicting multiple conformations remains a challenge. Therefore, it is essential to develop methods for predicting multiple conformations, which enable us to gain knowledge of multiple conformational states and the broader conformational landscape to better understand the mechanism of action. ResultsIn this work, we proposed a multiple conformational states folding method using the distance-based multi-objective evolutionary algorithm framework, named MultiSFold. First, a multi-objective energy landscape with multiple competing constraints generated by deep learning is constructed. Then, an iterative modal exploration and exploitation strategy based on multi-objective optimization, geometric optimization and structural similarity clustering is designed to perform conformational sampling. Finally, the final population is generated using a loop-specific perturbation strategy to adjust the spatial orientations. MultiSFold was compared with state-of-the-art methods on a developed benchmark testset containing 81 proteins with two representative conformational states. Based on the proposed metric, the success ratio of MultiSFold predicting multiple conformations was 70.4% while that of AlphaFold2 was 9.88%, which may indicate that conformational sampling combined with knowledge gained through deep learning has the potential to produce conformations spanned the range between two experimental structures. In addition, MultiSFold was tested on 244 human proteins with low structural accuracy in AlphaFold DB to test whether it could further improve the accuracy of static structures. The experimental results demonstrate that the TM-score of MultiSFold is 2.97% and 7.72% higher than that of AlphaFold2 and RoseTTAFold, respectively, supporting our hypothesis that multiple competing optimization objectives can further assist conformational search to improve prediction accuracy.

bioinformatics↗

bioRxiv2023

A zinc finger transcription factor tunes social behaviors by controlling transposable elements and immune response in prefrontal cortex

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in the rodent prefrontal cortex was previously determined to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Upon viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, dysregulation of ZFP189-mediated transcription in this brain area, achieved by delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. By performing RNA sequencing in virally manipulated prefrontal cortex tissues, we discover that ZFP189 transcription factors of opposing regulatory function have opposite influence on the expression of genetic transposable elements as well as genes that participate in immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for social behaviors by binding transposable element-rich regions of DNA to regulate immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animals capacity for functioning in social groups.

neuroscience↗

bioRxiv2023

Short Tandem Repeat Profiling via Next Generation Sequencing for Cell Line Authentication

Cell lines are indispensable models for modern biomedical research. In the era of CRISPR gene editing, they serve as versatile tools for preclinical studies, allowing patient specific mutations to be modeled or corrected and the resulting phenotypic outcomes studied. A large part of their usefulness derives from the ability of a cell line to proliferate over multiple passages (often indefinitely) allowing multiple experiments to be performed. However, over time, the cell line identity and purity can be compromised by human errors. Both cross contamination from other cell lines and even complete misidentification are possible. Routine cell line authentication is a necessary preventive measure and has become a requirement for many funding applications and publications. Short tandem repeat (STR) profiling is the most common method for cell line authentication and is usually carried out using standard polymerase chain reaction (PCR)-capillary electrophoresis (CE) analysis (STR-CE). Here we evaluated next generation sequencing (NGS)-based STR profiling of human and mouse cell lines at 18 and 15 loci, respectively, in a high-throughput format. Using the program STRight written in Python, we demonstrate that NGS-based analysis (STR-NGS) is superior to standard STR-CE in terms of the ability to report the sequence context of repeat motifs, sensitivity, and flexible multiplexing capability. STR-NGS is a valuable alternative for cell line authentication.

cell biology↗

bioRxiv2023

A Novel MHC-Independent Mechanism of Tumor Cell Killing by CD8+ T Cells

The accepted paradigm for both cellular and antitumor immunity relies upon tumor cell kill by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex class I (MHC I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8+T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent on interactions between T cell NKG2D and tumor NKG2D ligands (NKG2DL). Necessarily, tumor cell kill in these instances is antigen-independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumors cells. These mechanisms are active in vivo in mice, as well as in vitro in human tumor systems, and are obviated by NKG2D knockout or blockade. Tumor cell killing following T cell NKG2D engagement is Fas-independent and appears to involve granzyme. These studies potentially obviate the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape, and instead identify the NKG2D/NKG2DL axis as a novel therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC loss variants.

immunology↗

bioRxiv2023

GABA-mediated inhibition in visual feedback neurons fine-tunes Drosophila male courtship

Vision is critical for the regulation of mating behaviors in many species. Here, we discovered that the Drosophila ortholog of human GABAA-receptor-associated protein (GABARAP) is required to fine-tune male courtship by modulating the activity of visual feedback neurons, lamina tangential cells (Lat). GABARAP is a ubiquitin-like protein that regulates cell-surface levels of GABAA receptors. Knocking down GABARAP or GABAA receptors in Lat neurons or hyperactivating them induces male courtship toward other males. Inhibiting Lat neurons, on the other hand, delays copulation by impairing the ability of males to follow females. Remarkably, the human ortholog of Drosophila GABARAP restores function in Lat neurons. Using in vivo two-photon imaging and optogenetics, we show that Lat neurons are functionally connected to neural circuits that mediate visually-guided courtship pursuits in males. Our work reveals a novel physiological role for GABARAP in fine-tuning the activity of a visual circuit that tracks a mating partner during courtship.

neuroscience↗

bioRxiv2023

Sequencing of N6-methyl-deoxyadenosine at single-base resolution across the mammalian genome

While DNA N6-methyl-deoxyadenosine (6mA) is abundant in bacteria and protists, its presence and function in mammalian genomes have been less clear. We present Direct-Read 6mA sequencing (DR-6mA-seq), an antibody-independent method to measure 6mA at base-resolution with high sensitivity. DR-6mA-seq employs a unique mutation-based strategy to reveal 6mA sites as misincorporation signatures without any chemical or enzymatic modulation of 6mA. We validated DR-6mA-seq through successful mapping of the well-characterized G(6mA)TC motif in the E. coli DNA and identified 6mA sites in the mammalian mitochondrial DNA. As expected, when applying DR-6mA-seq to mammalian systems, we found that genomic DNA (gDNA) 6mA abundance is in general low in most mammalian tissues and cells; however, we did observe distinct gDNA 6mA sites in mouse testis and glioblastoma cells. DR-6mA-seq provides an enabling tool to detect 6mA at single-base resolution with high sensitivity for a comprehensive understanding of DNA 6mA in eukaryotes.

genetics↗

bioRxiv2023

A pilot study of stable isotope fractionation in Bombyx mori rearing

Hydrogen, oxygen, carbon, and nitrogen isotopes derived from three different strains of silkworms at different life stages involved in silkworm rearing, were measured to understand the fractionation characteristics of stable isotopes at different stages of silkworm development, and to trace the movement of these isotopes from food to larva to excrement and finally to silk. We found that silkworm strain had little effect on {delta}2H, {delta}18O and {delta}13C values. However, a large difference was found in the {delta}15N levels of newly-hatched silkworms between Jingsong Haoyue and Hua Kang No.3 orthogonal strains, suggesting that the mating and egg laying differences may result in an inconsistent kinetic nitrogen isotope fractionation. The {delta}13C values of silkworm pupae and silkworm cocoon also displayed significant differences, suggesting that heavy carbon isotopes are greatly fractionated from the larva to the silk during cocoon formation. Overall, these results may be used to clarify the relationship between isotope fractionation and the ecological process of the Bombyx mori and expand our ability to resolve stable isotope anomalies at a small regional-scale level.

biochemistry↗

bioRxiv2022

Inter-domain distance prediction based on deep learning for domain assembly

AlphaFold2 achieved a breakthrough in protein structure prediction through the end-to-end deep learning method, which can predict nearly all single-domain proteins at experimental resolution. However, the prediction accuracy of full-chain proteins is generally lower than that of single-domain proteins because of the incorrect interactions between domains. In this work, we develop an inter-domain distance prediction method, named DeepIDDP. In DeepIDDP, we design a neural network with attention mechanisms, where two new inter-domain features are used to enhance the ability to capture the interactions between domains. Furthermore, we propose a data enhancement strategy termed DPMSA, which is employed to deal with the absence of co-evolutionary information on targets. We integrate DeepIDDP into our previously developed domain assembly method SADA, termed SADA-DeepIDDP. Tested on a given multi-domain benchmark dataset, the accuracy of SADA-DeepIDDP inter-domain distance prediction is 11.3% and 21.6% higher than trRosettaX and trRosetta, respectively. The accuracy of the domain assembly model is 2.5% higher than that of SADA. Meanwhile, we reassemble 68 human multi-domain protein models with TM-score [≤]0.80 from the AlphaFold protein structure database, where the average TM-score is improved by 11.8% after the reassembly by our method. The online server is at http://zhanglab-bioinf.com/DeepIDDP/.

bioinformatics↗

bioRxiv2022

Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3

High-voltage-activated R-type CaV2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we determine the high-resolution cryo-electron microscopy (cryo-EM) structure of human CaV2.3 in complex with the 2{delta}1 and {beta}1 subunits. The VSDII is stabilized in the resting state. Electrophysiological experiments elucidate that the conformational change of VSDII in response to variation in membrane potential is not required for channel activation, whereas the other VSDs are essential for channel opening. The intracellular gate is blocked by the W-helix. A pre-W-helix adjacent to the W-helix can significantly regulate closed-state inactivation (CSI) by modulating the association and dissociation of the W-helix with the gate. Electrostatic interactions formed between the negatively charged domain on S6II, which is exclusively conserved in the CaV2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5II helix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of CaV2 channels.

biophysics↗

bioRxiv2022

Autophagy protects against high-dose Mycobacterium tuberculosis infection

Host autophagy had been associated with the control of Mycobacterium tuberculosis (Mtb) infection due to its ability to sequesters microorganisms through a process termed "xenophagy"1-4. Xenophagy purportedly limits Mtb replication within infected macrophages1-4. However, studies in mice using a standard low-dose infection model demonstrated that xenophagy in infected phagocytes is not required to control Mtb pathogenesis5,6. Instead, an autophagy-independent function of ATG5 in myeloid cells controls low-dose Mtb infection through limiting neutrophilic inflammation5. Hitherto, an in vivo role for autophagy during Mtb infection remained to be elucidated. We report herein that autophagy in myeloid cells mediates protection against high-dose Mtb infection, providing the first evidence for a role for autophagy in myeloid cells during Mtb infection in vivo. With the exception of ATG5, the autophagy proteins required to control high-dose Mtb infection are dispensable for host defense against a standard low-dose Mtb infection. Specifically, autophagy is required in CD11c+ cells, but is dispensable in neutrophils, to control a high-dose Mtb infection in the lung. The role for autophagy is not to directly degrade Mtb in macrophages through xenophagy, but mainly to limit myeloid-derived suppressor cell accumulation and to promote sustained protective T cell responses. Together, our data highlight a novel role for autophagy in controlling Mtb infection, distinct from that of Atg5 during low-dose Mtb infection, or any previously reported roles for autophagy. In addition, our finding that the result of a pathogen-plus-susceptibility gene interaction is dependent on pathogen burden has important implications on our understanding of how Mtb infection in humans can lead to a spectrum of outcomes, the variables that contribute to autophagy gene function during infection and inflammation, and the potential use of autophagy modulators in clinical medicine.

microbiology↗

bioRxiv2022

Born with intronless ERF transcriptional factors: C4 photosynthesis inherits a legacy dating back 450 million years

The genus Flaveria, containing species at different evolutionary stages of the progression from C3 to C4 photosynthesis, is used as a model system to study the evolution of C4 photosynthesis. Here, we report chromosome-scale genome sequences for five Flaveria species, including C3, C4, and intermediate species. Our analyses revealed that both acquiring additional gene copies and recruiting ethylene responsive factor (ERF) cis-regulatory elements (CREs) contributed to the emergence of C4 photosynthesis. ERF transcriptional factors (TFs), especially intronless ERF TFs, were co-opted in dicotyledonous C4 species and monocotyledonous C4 species in parallel. These C4 species co-opted intronless ERF TFs originated from the Late Ordovician mass extinction that occurred [~]450 million years ago in coping with environmental stress. Therefore, this study demonstrated that intronless ERF TFs were acquired during the early evolution of plants and provided the molecular toolbox facilitating multiple subsequent independent evolutions of C4 photosynthesis.

evolutionary biology↗

bioRxiv2022

Bioinformatic-based identification of 3 immune-related genes for prognostic in breast invasive carcinoma

Breast invasive carcinoma (BRCA) is the leading cause of cancer deaths in female worldwide. Immune cell infiltration is considered to be crucial factor for the success or failure of BRCA therapy. As we all known, early diagnosis of breast cancer can greatly improve the survival rate of patients. Hence, to screen effective biomarkers for breast cancer immunotherapy might be extremely important. In this research, we identified an immune-related, three-gene biomarkers for prognosis of BRCA. We obtained altogether 192 differentially expressed genes (DEGs) from GEO datasets (GSE22820, GSE36295) and GEPIA database, followed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We screened 3 immune-related candidate biomarkers composing by CXCL2, CXCL9 and RBP7 that improves survival prediction outcome in BRCA. Kaplan-Meier analysis was conducted to analyze the patient survival based on 3 genes. In addition, we found that selected biomarkers were closely connected with infiltration levels of different tumor immune cells. Moreover, principal component analysis showed three biomarkers could effectively distinguish tumor samples from normal samples. In summary, these findings suggested that CXCL2, CXCL9 and RBP7 are viable prognostic and diagnostic biomarkers and provide new ideas for immunotherapy solutions of BRCA in the future.

bioinformatics↗

bioRxiv2022

A SHR-IDD-PIN regulatory network mediates minor vein differentiation in rice

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Here we define a genetic circuit comprised of SHR, IDD and PIN family members that specify vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHORT ROOT (SHR) paralogs in C3 Oryza sativa (rice) and C4 Setaria viridis (green millet) revealed a role in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggest that SHR regulates this process through its interaction with Indeterminate Domain (IDD) IDD 12 and 13. We further show a direct interaction of these IDD proteins with a putative regulatory element within the auxin transporter PIN5c gene. Collectively, these studies indicated that a SHR-IDD regulatory circuit mediates auxin flow through the negative regulation of PIN protein expression to modulate minor vein patterning in the grasses.

plant biology↗

bioRxiv2022

CoAtGIN: Marrying Convolution and Attention for Graph-based Molecule Property Prediction

Molecule property prediction based on computational strategy plays a key role in the process of drug discovery and design, such as DFT. Yet, these traditional methods are time-consuming and labour-intensive, which cant satisfy the need of biomedicine. Thanks to the development of deep learning, there are many variants of Graph Neural Networks (GNN) for molecule representation learning. However, whether the existed well-perform graph-based methods have a number of parameters, or the light models cant achieve good grades on various tasks. In order to manage the trade-off between efficiency and performance, we propose a novel model architecture, CoAtGIN, using both Convolution and Attention. On the local level, k-hop convolution is designed to capture long-range neighbour information. On the global level, besides using the virtual node to pass identical messages, we utilize linear attention to aggregate global graph representation according to the importance of each node and edge. In the recent OGB Large-Scale Benchmark, CoAtGIN achieves the 0.0933 Mean Absolute Error (MAE) on the large-scale dataset PCQM4Mv2 with only 5.6 M model parameters. Moreover, using the linear attention block improves the performance, which helps to capture the global representation.

bioinformatics↗

bioRxiv2022

Glabridin induces paraptosis-like cell death via ER stress in breast cancer cells

Glabridin, a polyphenolic flavonoid isolated from the root of the glycyrrhiza glabra, has been demonstrated to have anti-tumor properties in human malignancies. This study found that glabridin decreased the viability of human breast cancer MDA-MB-231 and MCF7 cells in a dose-dependent manner that was not involved in the caspase-3 cascade. Glabridin promoted the formation of extensive cytoplasmic vacuolation by increasing the expression of endoplasmic reticulum (ER) stress markers BiP, XBP1s, and CHOP. The transmission electron microscopy and fluorescence with the ER chaperon KDEL suggested that the vacuoles were derived from ER. Glabridin-induced vacuolation was blocked when protein synthesis was inhibited by cycloheximide, demonstrating that protein synthesis is crucial for this process. Furthermore, we determined that glabridin causes loss of mitochondrial membrane potential as well as the production of reactive oxygen species, both of which lead to mitochondrial dysfunction. These features are consistent with a kind of programmed cell death described as paraptosis. This work reports for the first time that glabridin could induce paraptosis-like cell death, which may give new therapeutic approaches for apoptosis-resistant breast cancers.

cell biology↗

bioRxiv2022

Adrenal sympathetic nerve mediated the anti-inflammatory effect of electroacupuncture at ST25 acupoint on a rat model of sepsis

Acupuncture plays a vital anti-inflammatory action on sepsis through activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating sympathoadrenal medullary pathway and evaluate EAs anti-inflammatory effect on sepsis. To explore the optimum parameter of EA at homosegmental acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley (SD) rats were evaluated by in vivo electrophysiological recording, and the levels of norepinephrine (NE) and its metabolites were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rat was given intraperitoneal injection lipopolysaccharide to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1{beta}, and IL-10 were evaluated after EA application. We observed that 3 mA is the optimal intensity on activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3 mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1{beta} and upregulated anti-inflammatory cytokine IL-10 compared to the Lipopolysaccharide (LPS)-treated group. Overall, these data suggest that 3 mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect on sepsis. HighlightsO_LI3 mA single shock ES at ST25 drove adrenal sympathetic nerve reflexs. C_LIO_LI3 mA EA at ST25 upregulated NE concentration in peripheral blood. C_LIO_LIEA at ST25 improved the survival rate in a rat of LPS-induced sepsis model. C_LIO_LIEA at the ST25 upregulated anti-inflammatory IL10 and downregulated pro-inflammatory IL1{beta} and IL-6 in LPS-treated rats. C_LI

neuroscience↗