Biology subjects

Lu, L.

Publications and source records attributed to Lu, L..

At least 199 records · Page 11Linked to original sources

bioRxiv2019

Evolutionary origins of epidemic potential among human RNA viruses

To have epidemic potential, a pathogen must be able to spread in human populations, but of human-infective RNA viruses only a minority can do so. We investigated the evolution of human transmissibility through parallel analyses of 1755 virus genome sequences from 39 RNA virus genera. We identified 57 lineages containing human-transmissible species and estimated that at least 74% of these lineages have evolved directly from non-human viruses in other mammals or birds, a public health threat recently designated \"Disease X\". Human-transmissible viruses rarely evolve from virus lineages that can infect but not transmit between humans. This result cautions against focussing surveillance and mitigation efforts narrowly on currently known human-infective virus lineages and supports calls for a better understanding of RNA virus diversity in non-human hosts.

evolutionary biology↗

bioRxiv2019

KDDANet-a novel computational framework for systematic uncovering hidden gene interactions underlying known drug-disease associations

Many of genes mediating Known Drug-Disease Association (KDDA) are escaped from experimental detection. Identifying of these genes (hidden genes) is of great significance for understanding disease pathogenesis and guiding drug repurposing. Here, we presented a novel computational tool, called KDDANet, for systematic and accurate uncovering the hidden genes mediating KDDA from the perspective of genome-wide functional gene interaction network. KDDANet demonstrated the competitive performances in both sensitivity and specificity of identifying genes in mediating KDDA in comparison to the existing state-of-the-art methods. Case studies on Alzheimers disease (AD) and obesity uncovered the mechanistic relevance of KDDANet predictions. Furthermore, when applied with multiple types of cancer-omics datasets, KDDANet not only recapitulated known genes mediating KDDAs related to cancer, but also revealed novel candidates that offer new biological insights. Importantly, KDDANet can be used to discover the shared genes mediating multiple KDDAs. KDDANet can be accessed at http://www.kddanet.cn and the code can be freely downloaded at https://github.com/huayu1111/KDDANet.

bioinformatics↗

bioRxiv2019

A reference library for the identification of Canadian invertebrates: 1.5 million DNA barcodes, voucher specimens, and genomic samples

The reliable taxonomic identification of organisms through DNA sequence data requires a well parameterized library of curated reference sequences. However, it is estimated that just 15% of described animal species are represented in public sequence repositories. To begin to address this deficiency, we provide DNA barcodes for 1,500,003 animal specimens collected from 23 terrestrial and aquatic ecozones at sites across Canada, a nation that comprises 7% of the planets land surface. In total, 14 phyla, 43 classes, 163 orders, 1123 families, 6186 genera, and 64,264 Barcode Index Numbers (BINs; a proxy for species) are represented. Species-level taxonomy was available for 38% of the specimens, but higher proportions were assigned to a genus (69.5%) and a family (99.9%). Voucher specimens and DNA extracts are archived at the Centre for Biodiversity Genomics where they are available for further research. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, and the Global Genome Biodiversity Network Data Portal.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC=\"FIGDIR/small/701805v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (17K):\norg.highwire.dtl.DTLVardef@5c6449org.highwire.dtl.DTLVardef@1bc0224org.highwire.dtl.DTLVardef@309dddorg.highwire.dtl.DTLVardef@1cc2cc8_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2019

GEOlimma: Differential Expression Analysis and Feature Selection Using Pre-Existing Microarray Data

BackgroundDifferential expression and feature selection analyses are essential steps for the development of accurate diagnostic/prognostic classifiers of complicated human diseases using transcriptomics data. These steps are particularly challenging due to the curse of dimensionality and the presence of technical and biological noise. A promising strategy for overcoming these challenges is the incorporation of pre-existing transcriptomics data in the identification of differentially expressed (DE) genes. This approach has the potential to improve the quality of selected genes, increase classification performance, and enhance biological interpretability. While a number of methods have been developed that use pre-existing data for differential expression analysis, existing methods do not leverage the identities of experimental conditions to create a robust metric for identifying DE genes.\n\nResultsIn this study, we propose a novel differential expression and feature selection method--GEOlimma--which combines pre-existing microarray data from the Gene Expression Omnibus (GEO) with the widely-applied Limma method for differential expression analysis. We first quantify differential gene expression across 2481 pairwise comparisons from 602 curated GEO Datasets, and we convert differential expression frequencies to DE prior probabilities. Genes with high DE prior probabilities show enrichment in cell growth and death, signal transduction, and cancer-related biological pathways, while genes with low prior probabilities were enriched in sensory system pathways. We then applied GEOlimma to four differential expression comparisons within two human disease datasets and performed differential expression, feature selection, and supervised classification analyses. Our results suggest that use of GEOlimma provides greater experimental power to detect DE genes compared to Limma, due to its increased effective sample size. Furthermore, in a supervised classification analysis using GEOlimma as a feature selection method, we observed similar or better classification performance than Limma given small, noisy subsets of an asthma dataset.\n\nConclusionsOur results demonstrate that GEOlimma is a more effective method for differential gene expression and feature selection analyses compared to the standard Limma method. Due to its focus on gene-level differential expression, GEOlimma also has the potential to be applied to other high-throughput biological datasets.

bioinformatics↗

bioRxiv2019

The expanded BXD family of mice: A cohort for experimental systems genetics and precision medicine

The challenge of precision medicine is to model complex interactions among DNA variants, sets of phenotypes, and complex environmental factors and confounders. We have expanded the BXD family, creating a powerful and extensible test bed for experimental precision medicine and an ideal cohort to study gene-by-environmental interactions.\n\nThese BXD segregate for over 6 million variants, with a mean minor allele frequency close to 0.5. We have increased the family two-fold to 150 inbred strains, all derived from C57BL/6J and DBA/2J. We have also generated updated and comprehensive genotypes and an unrivaled deep phenome.\n\nApproximately 10,000 recombinations have been located, allowing precision of quantitative trait loci mapping of {+/-}2.0 Mb over much of the genome and {+/-}0.5 Mb for Mendelian loci. The BXD phenome includes more than 100 omics data sets and >7000 quantitative and clinical phenotypes, all of which is publicly available.\n\nThe BXD family is an enduring, collaborative, and replicable resource to test causal and mechanistic links between genomes and phenomes at many stages and under a wide variety of treatments and interventions.

genomics↗

bioRxiv2019

Modular and efficient pre-processing of single-cell RNA-seq

Analysis of single-cell RNA-seq data begins with pre-processing of sequencing reads to generate count matrices. We investigate algorithm choices for the challenges of pre-processing, and describe a workflow that balances efficiency and accuracy. Our workflow is based on the kallisto (https://pachterlab.github.io/kallisto/) and bustools (https://bustools.github.io/) programs, and is near-optimal in speed and memory. The workflow is modular, and we demonstrate its flexibility by showing how it can be used for RNA velocity analyses. Documentation and tutorials for using the kallisto | bus workflow are available at https://www.kallistobus.tools/.

bioinformatics↗

bioRxiv2019

A Clostridia-rich microbiota contributes to increased excretion of bile acids in diarrhea-predominant irritable bowel syndrome

ObjectiveAn excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remains unclear. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D.\n\nDesignMetabolomic and metagenomic analyses were performed of specimens from 290 IBS-D patients and 89 healthy volunteers. By transplanting human microbiota and manipulating specific microbiome species in mice, the effects of microbiota on host BA metabolism were assessed at metabolic, genetic and protein levels. Effects of individual and mixed BAs on enterohepatic feedback pathways were also tested in vitro and in vivo.\n\nResultsTotal fecal BAs were excessively excreted in 24.5% of IBS-D patients. Their fecal metagenomes showed increased abundances of Clostridia and BA-transforming genes (hdhA and bais). The increases of Clostridia bacteria (e.g. C. scindens) were positively associated with the levels of fecal BAs and serum 7-hydroxy-4-cholesten-3-one (C4), while being negatively correlated with serum fibroblast growth factor 19 (FGF19). Both Clostridia-rich human microbiota and C. scindens enhanced levels of serum C4 and hepatic conjugated BAs in mice recipients and reduced ileal FGF19 expression. Inhibition of Clostridium species by vancomycin yielded opposite findings. Clostridia-derived BAs (e.g. conjugated and free ursodeoxycholic acid) significantly suppressed intestinal FGF19 expression.\n\nConclusionThe Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients. This study provided the basis for more precise clinical diagnosis and management for IBS-D.

microbiology↗

bioRxiv2019

Prognostic Analysis of Histopathological Images Using Pre-Trained Convolutional Neural Networks

BackgroundHistopathological images contain rich phenotypic descriptions of the molecular processes underlying disease progression. Convolutional neural networks (CNNs), a state-of-the-art image analysis technique in computer vision, automatically learns representative features from such images which can be useful for disease diagnosis, prognosis, and subtyping. Despite hepatocellular carcinoma (HCC) being the sixth most common type of primary liver malignancy with a high mortality rate, little previous work has made use of CNN models to delineate the importance of histopathological images in diagnosis and clinical survival of HCC.\n\nResultsWe applied three pre-trained CNN models - VGG 16, Inception V3, and ResNet 50 - to extract features from HCC histopathological images. The visualization and classification showed clear separation between cancer and normal samples using image features. In a univariate Cox regression analysis, 21.4% and 16% of image features on average were significantly associated with overall survival and disease-free survival, respectively. We also observed significant correlations between these features and integrated biological pathways derived from gene expression and copy number variation. Using an elastic net regularized CoxPH model of overall survival, we obtained a concordance index (C-index) of 0.789 and a significant log-rank test (p = 7.6E-18) after applying Inception image features. We also performed unsupervised classification to identify HCC subgroups from image features. The optimal two subgroups discovered using Inception image features were significantly associated with both overall (C-index = 0.628 and p = 7.39E-07) and disease-free survival (C-index =0.558 and p = 0.012). Our results suggest the feasibility of feature extraction using pre-trained models, as well as the utility of the resulting features to build an accurate prognosis model of HCC and highlight significant correlations with clinical survival and biological pathways.\n\nConclusionsThe image features extracted from HCC histopathological images using the pre-trained CNN models VGG 16, Inception V3 and ResNet 50 can accurately distinguish normal and cancer samples. Furthermore, these image features are significantly correlated with relevant biological outcomes.

bioinformatics↗

bioRxiv2019

Fenoxaprop-p-ethyl susceptibility and mutation point detection of acetyl-coa carboxylase (ACCase) in different wild oat (Avena fatua L.) populations from China

To explore resistant mechanism of wild oat to fenoxaprop-p-ethyl, the susceptibility of Acetyl-CoA Carboxylase (ACCase) from 24 wild oat populations to fenoxaprop-p-ethyl, the level of gene expression, and mutation site of ACCase were conducted. In vitro ACCase activities were solated and measured by enzyme-linked immunosorbent assay kit (ELISA) assays, the results indicated that the IC50 value of the ACCase of the most unsusceptible to fenoxaprop-p-ethyl in the wild oat population from Yexian2017 (W24) was 7206.557-fold compared to that of the ACCase of most susceptible to fenoxaprop-p-ethyl in the wild oat population from Queshan (W11). The differential expression of genes in wild oat treated by the IC50 fenoxaprop-p-ethyl concentration (6.9 mg/L) for 24 hours using RNA-seq, digital gene expression (DGE) profling was conducted. We found that 8 unigenes annotated as ACCase genes, 0 up-regulaed expression and 3 down-regulated expression were observed. The down-regulaed expressed ACCase was selected for qPCR in the relative susceptible population were significantly more suppressed than the three relative resistant populations. The mutations point of ACCase, Ile-1781-Leu, Trp-1999-Cys, Trp-2027-Cys, Ile-2041-Asn, Asp-2078-Gly, Cys-2088-Arg published were not found in the populations tested by multiple sequence alignment with a model complete ACCase sequence of Alopecurus myosuroides. These findings suggest that ACCase plays a critical role in the development of wild oat resistance to fenoxaprop-p-ethyl.

molecular biology↗

bioRxiv2019

Identification of a functional non-coding variant in the GABAA receptor α2 subunit of the C57BL/6J mouse reference genome: Major implications for neuroscience research

GABA type-A (GABA-A) receptors containing the 2 subunit (Gabra2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of Gabra2 brain mRNA and protein in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair intronic deletion located adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR-Cas9 mediated gene editing on a B6J genetic background completely restored brain levels of Gabra2 mRNA and protein. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the Gabra2 gene is of critical importance to molecular genetic studies in neurobiological research as this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by Gabra2 function.

genetics↗

bioRxiv2019

Genetic dissection of femoral and tibial microarchitecture

Our understanding of the genetic control of bone has relied almost exclusively on estimates of bone mineral density. In contrast, here we have used high-resolution x-ray tomography (8 m isotropic voxels) to measure femoral and tibial components across a set of ~600 mice belonging to 60 diverse BXD strains of mice. We computed heritabilities of 25 cortical and trabecular compartments. Males and females have well matched trait heritabilities, ranging from 0.25 to 0.75. We mapped 16 QTLs that collectively cover ~8% of all protein-coding genes in mouse. A majority of loci are detected only in females, and there is also a bias in favor of QTLs for cortical traits. To efficiently evaluate candidate genes we developed a method that couples gene ontologies with expression data to compute bone-enrichment scores for almost all protein-coding genes. We carefully collated and aligned murine candidates with recent human BMD genome-wide association results. We highlight a subset of 50 strong candidates that fall into three categories: 1. those linked to bone function that have already been experimentally validated (Adamts4, Ddr2, Darc, Adam12, Fkbp10, E2f6, Adam17, Grem2, Ifi204); 2. candidates with putative bone function but not yet tested (e.g., Greb1, Ifi202b) but several of which have been linked to phenotypes in humans; and 3. candidates that have high bone-enrichment scores but for which there is not yet any specific link to bone biology or skeletal disease, including Ifi202b, Ly9, Ifi205, Mgmt, F2rl1, Iqgap2. Our results highlight contrasting genetic architecture between the sexes and among major bone compartments. The joint use and alignment of murine and human data should greatly facilitate function analysis and preclinical testing.\n\nDisclosureThe authors declare that no competing interests exist.

genetics↗

bioRxiv2018

Genome-wide association study identifies common genetic risk factors for alcohol, heroin and methamphetamine dependence

BackgroundCommon molecular and cellular foundations underlie different types of substance dependence (SD). However direct evidence for common genetic factors of SD is lacking. Here we aimed to identify specific genetic variants that are shared between alcoholism, heroin and methamphetamine dependence.\n\nMethodsWe first conducted a combined case-control genome-wide association analysis (GWAS) of 521 alcoholic, 1,026 heroin and 1,749 methamphetamine patients and 2,859 healthy controls. We then replicated the significant loci using an independent cohort (146 alcoholic, 1,045 heroin, 763 methamphetamine and 1,904 controls). Second, we examined the genetic effects of these identified SNPs on gene expression, addiction characteristics and brain images (gray and white matter). Furthermore, we investigated the effects of these genetic variants on addiction behaviors using self-administration rat models.\n\nResultsWe identified and validated four genome-wide significant loci in the combined cohorts in the discovery stage: ADH1B rs1229984 (P=6.45x10-10), ANKS1B rs2133896 (P=4.09x10-8), AGBL4 rs147247472 (P=4.30x10-8) and CTNNA2 rs10196867 (P=4.67x10-8). Association results for each dependence group showed that ADH1B rs1229984 was only associated with alcoholism, while the other three loci were associated with heroin, methamphetamine addiction and alcoholism respectively. Variants that were strongly linked to rs2133896 affected ANKS1B gene expression, heroin use frequency and interacted with heroin dependence to affect gray matter of the left calcarine and white matter of the right superior longitudinal fasciculus. In addition, the reduced anks1b expression in the ventral tegmental area increased addiction vulnerability for heroin and methamphetamine in self-administration rat models.\n\nConclusionOur findings revealed several novel genome-wide significant SNPs and genes that synchronously affected the vulnerability and phenotypes for alcoholism, heroin and MA dependence. These findings could shed light on the root cause and the generalized vulnerability for SD.

genomics↗

bioRxiv2018

Exploring differentially expressed key genes related to development of follicle by RNA-seq in Peking ducks (Anas Platyrhynchos)

Duck follicle enter different reproductive phases throughout life, and follicle gene expression patterns differ according to these phases. In particular, differentially expressed genes and related to development of follicle (mRNAs) play an important role to explore the key genes in this process; however, the expression profiles of these genes remain unclear. In this study, transcriptome sequencing was used to investigate the expression levels of duck ovarian genes, and comparative transcriptional analysis was carried out to identify differential genes, cluster them into groups and function identification. The results showed differential expression of 593 coding genes between young and laying ducks, and of 518 coding genes between laying and old ducks. In further GO analysis, 35 genes from the comparison bewtween old ducks and laying ducks have significant been changed involved in hormones related to follicle development. They include up-regulated genes StAR, CYP17, EPOX, 3{beta}-HSD, CYP1B1 CYP19A1 and down-regulated genes SR-B1 in laying ducks hormone synthesis than old ducks. Among which EPOX is a key gene for time special highly expression during egg laying stage, and other key regulatory genes highly expression showed in young and laying stage and lower expression showing with follicular development stopping. Therefore, EPOX is key regulator for duck follicle development in laying period, when its expression level decrease 98% the follicular development will stopping in duck life cycle.

developmental biology↗

bioRxiv2018

Diagnostic Whole Exome Sequencing in Patients with Short Stature

Short stature is among the most common reasons for children being referred to the pediatric endocrinology clinics. The cause of short stature is broad, in which genetic factors play a substantial role, especially in primary growth disorders. However, identifying the molecular causes for short stature remains as a challenge because of the high heterogeneity of the phenotypes. Here, whole exome sequencing (WES) was used to identify the genetic causes of short stature with unknown etiology for 20 patients aged from 1 to 16 years old. The genetic causes of short stature were identified in 9 of the 20 patients, corresponding to a molecular diagnostic rate of 45%. Notably, in 2 of the 9 patients identified with genetic causes, the diagnosed diseases based on WES are different from the original clinical diagnosis. Our results highlight the clinical utility of WES in the diagnosis of rare, high heterogeneity disorders.

genetics↗

bioRxiv2018

Two key events associated with a transposable element burst occurred during rice domestication

Transposable elements shape genome evolution through periodic bursts of amplification. In this study we exploited knowledge of the components of the mPing/Ping/Pong TE family in four rice strains undergoing mPing bursts to track their copy numbers and distribution in a large collection of genomes from the wild progenitor Oryza rufipogon and domesticated Oryza sativa (rice). We characterized two events that occurred to the autonomous Ping element and appear to be critical for mPing hyperactivity. First, a point mutation near the end of the element created a Ping variant (Ping16A) with reduced transposition. The proportion of strains with Ping16A has increased during domestication while the original Ping (Ping16G) has been dramatically reduced. Second, transposition of Ping16A into a Stowaway element generated a locus (Ping16A_Stow) whose presence correlates with strains that have high mPing copies. Finally, demonstration that Pong elements have been stably silenced in all strains analyzed indicates that sustained activity of the mPing/Ping family during domestication produced the components necessary for the mPing burst, not the loss of epigenetic regulation.

genomics↗

bioRxiv2018

Increased GITRL impairs the function of MDSCs and exacerbates primary Sjögren’s syndrome

It is largely unclear how MDSCs contribute to the development of primary Sjogrens syndrome (pSS). In experimental SS (ESS) mice, MDSCs were significantly increased but exhibited gradually diminished suppressive capacity during the disease progression. The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased with the development of pSS, and the increased GITRL was found to down-regulate the function of MDSCs while blocking GITR signal in MDSCs significantly restored their function and ameliorated ESS progression in mice. In pSS patients, expanded MDSCs expressed lower level of arginase were observed in patients with higher SSDAI. Moreover, the increased GITRL in serum was also found to closely correlate with the aberrant function of MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive capacity of MDSCs in pSS, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.

immunology↗

bioRxiv2018

TRAF6 directs Foxp3 localization and facilitates Treg function through K63-type ubiquitination

Regulatory T cells (Treg) are crucial mediators of immune control. The characteristic gene expression and suppressive function of Treg depend considerably on the stable expression and activity of the transcription factor Foxp3. While transcriptional regulation of the Foxp3 gene has been studied in depth, both the expression and function of Foxp3 are also modulated at the protein level. However, the molecular players involved in posttranslational Foxp3 regulation are just beginning to be elucidated. Here we found TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to B16 melanomas and displayed enhanced anti-tumor immunity. We further determined that Foxp3 undergoes lysine-63 chain (K63) ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. When deprived of TRAF6 activity or rendered insensitive to K63 ubiquitination, Foxp3 displayed aberrant, perinuclear accumulation, disrupted function. Thus, Foxp3 ubiquitination by TRAF6 ensures proper localization of Foxp3 and facilitates Foxp3s gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing force that may be targeted in novel tolerance-breaking therapies.

immunology↗

bioRxiv2018

Nonmuscle myosin II shRNA inhibit migration and contraction in rat hepatic stellate cells through regulating AKT/mTOR/S6K/4EBP1 signaling pathway

Migration and contraction of activated hepatic stellate cell (HSC) are essential factors for cirrhosis formation and development. It has been demonstrated that blebbistatin, a nonmuscle myosin II (NMMII) inhibitor, can inhibit the migration and contraction of HSC, whereas the main cell signaling pathway is still unknown. Mammalian target of rapamycin (mTOR) signaling pathway may be involved in many cells migration and contraction, whether NMMII and mTOR have any crosslinks draw our attention. In the currently study, we used LV-RNAi to specifically attenuate mTOR and NMMII in rat HSC. We aimed to examine the effect of mTOR LV-RNAi on the migration and contraction of HSC and explore the crosslink between mTOR cell signal and NMMII. Using real-time PCR and western blot, we found that mTOR and the downstream factors including S6K and 4EBP1 all up-regulated with the activation of HSC, mTOR and NMMII LV-RNAi was transfected into activated HSC using lipofectamine 2000. The levels of mRNA and proteins were also examined using real-time PCR and western blot respectively. The expression of mTOR can be down-regulated by NMMII LV-RNAi significantly, as well as the expression of S6K, 4EBP1, -SMA and collagen I, but the level of AKT was up-regulated. Then we used Transwell system and collagen lattices to examine the NMMII and mTOR LV-RNAi efficiency on HSC migration and contraction, as we hypothesized, both of the LV-RNAi could inhibit HSC migration and contraction significantly. These results indicated that nonmuscle myosin II shRNA inhibit migration and contraction in rat hepatic stellate cells through the regulation of mTOR/S6K/4EBP1 signaling pathway

cell biology↗