CRISPR-Cpf1 system and its applications in animal genome editing.

The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein (Cas) system is a gene editing technology guided by RNA endonuclease. The CRISPR-Cas12a (also known as CRISPR-Cpf1) system is extensively utilized in genome editing research due to its accuracy and high efficiency. In this paper, we primarily focus on the application of CRISPR-Cpf1 technology in the construction of disease models and gene therapy. Firstly, the structure and mechanism of the CRISPR-Cas system are introduced. Secondly, the similarities and differences between CRISPR-Cpf1 and CRISPR-Cas9 technologies are compared. Thirdly, the main focus is on the application of the CRISPR-Cpf1 system in cell and animal genome editing. Finally, the challenges faced by CRISPR-Cpf1 technology and corresponding strategies are analyzed. Although CRISPR-Cpf1 technology has certain off-target effects, it can effectively and accurately edit cell and animal genomes, and has significant advantages in the preclinical research.

Bioleaching performance of vanadium-bearing smelting ash by Acidithiobacillus ferrooxidans for vanadium recovery.

The bioleaching process is widely used in the treatment of ores or solid wastes, but little is known about its application in the treatment of vanadium-bearing smelting ash. This study investigated bioleaching of smelting ash with Acidithiobacillus ferrooxidans. The vanadium-bearing smelting ash was first treated with 0.1 M acetate buffer and then leached in the culture of Acidithiobacillus ferrooxidans. Comparison between one-step and two-step leaching process indicated that microbial metabolites could contribute to the bioleaching. The Acidithiobacillus ferrooxidans demonstrated a high vanadium leaching potential, solubilizing 41.9% of vanadium from the smelting ash. The optimal leaching condition was determined, which was 1% pulp density, 10% inoculum volume, an initial pH of 1.8, and 3 Fe2+g/L. The compositional analysis showed that the fraction of reducible, oxidizable, and acid-soluble was transferred into the leaching liquor. Therefore, as the alternative to the chemical/physical process, an efficient bioleaching process was proposed to enhance the recovery of vanadium from the vanadium-bearing smelting ash.

Serum long non-coding RNA SCARNA10 serves as a potential diagnostic biomarker for hepatocellular carcinoma.

BACKGROUND: Circulating long non-coding RNAs (lncRNAs) have been demonstrated to serve as diagnostic or prognosis biomarkers for various disease. We aimed to elucidate the diagnostic efficacy of serum lncRNA SCARNA10 for the hepatocellular carcinoma (HCC). METHODS: In this study, a total of 182 patients with HCC, 105 patients with benign liver disease (BLD), and 149 healthy controls (HC) were enrolled. According to different classifications, the levels of serum SCARNA10 were assessed by quantitative real-time polymerase chain reaction (qPCR). The correlations between serum SCARNA10 and clinicopathological characteristics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum SCARNA10 and its combination with AFP for HCC. RESULTS: The results demonstrated that the levels of serum SCARNA10 were significantly higher in HCC patients than in patients with BLD and healthy controls, and significantly increased in HCC patients with hepatitis B or C infection, or with liver cirrhosis. Furthermore, positive correlations were noted between serum SCARNA10 level and some clinicopathological characteristics, including tumor size, differentiation degrees, tumor stage, vascular invasion, tumor metastasis and complications. ROC analysis revealed that SCARNA10 had a significantly predictive value for HCC (Sensitivity = 0.70, Specificity = 0.77, and AUC = 0.82), the combination of SCARNA10 and AFP gained the higher sensitivity (AUCSCARNA10 + AFP = 0.92 vs AUCAFP = 0.83, p <  0.01). SCARNA10 retained significant diagnosis capabilities for AFP-negative HCC patients. CONCLUSIONS: In summary, lncRNA SCARNA10 may serve as a novel and non-invasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.

Knockout of CTNNB1 by CRISPR-Cas9 technology inhibits cell proliferation through the Wnt/ß-catenin signaling pathway.

OBJECTIVE: To study the effects of CTNNB1 gene knockout by CRISPR-Cas9 technology on cell adhesion, proliferation, apoptosis, and Wnt/ß-catenin signaling pathway. RESULTS: CTNNB1 gene of HEK 293T cells was knocked out by CRISPR-Cas9. This was confirmed by sequencing and western blotting. Methylthiazolyl-tetrazolium bromide assays indicated that deletion of ß-catenin significantly weakened adhesion ability and inhibited proliferation rate (P < 0.01) of HEK 293T cells. Nevertheless, deletion of ß-catenin did not affect apoptosis of HEK 293T cells, which was analyzed by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. In addition, expression level of GSK-3ß, CCND1, and CCNE1 detected by qPCR and expression level of N-Cadherin and cyclin D1 detected by western blotting were significantly decreased (P < 0.01) while expression of γ-catenin detected by western blotting was significantly increased (P < 0.001). CONCLUSIONS: Knockout of CTNNB1 disturbed Wnt/ß-catenin signaling pathway and significantly inhibited adhesion and proliferation of HEK 293T cells.

BAG-1M co-activates BACE1 transcription through NF-κB and accelerates Aß production and memory deficit in Alzheimer's disease mouse model.

Accumulation of amyloid ß protein (Aß)-containing neuritic plaques in the brain is a neuropathological feature of Alzheimer's disease (AD). The ß-site APP-cleaving enzyme 1 (BACE1) is essential for Aß generation and dysregulation of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M (BAG-1M), initially identified as an anti-apoptotic protein, has also been found to be highly expressed in the same neurons that contain intracellular amyloid in the hippocampus of AD patient. In this report, we found that over-expression of BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and Aß production by up-regulating BACE1 gene transcription. The regulation of BACE1 transcription by BAG-1M was dependent on NF-κB, as BAG-1M complexes NF-κB at the promoter of BACE1 gene and co-activates NF-κB-facilitated BACE1 transcription. Moreover, expression of BAG-1M by lentiviral vector in the hippocampus of AD transgenic model mice promotes Aß generation and formation of neuritic plaque, and subsequently accelerates memory deficits of the mice. These results provide evidence for an emerging role of BAG-1M in the regulation of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-κB complex may provide a mechanism for inhibiting Aß production and plaque formation.

YAP and TAZ Take Center Stage in Cancer.

The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.

Deciphering Vanadium Speciation in Smelting Ash and Adaptive Responses of Soil Microorganisms.

Abundant smelting ash is discharged during pyrometallurgical vanadium (V) production. However, its associated V speciation and resultant ecological impact have remained elusive. In this study, V speciation in smelting ash and its influence on the metabolism of soil microorganisms were investigated. Smelting ashes from V smelters contained abundant V (19.6-115.9 mg/g). V(V) was the dominant species for soluble V, while solid V primarily existed in bioavailable forms. Previously unrevealed V nanoparticles (V-NPs) were prevalently detected, with a peak concentration of 1.3 × 1013 particles/g, a minimal size of 136.0 ± 0.6 nm, and primary constituents comprising FeVO4, VO2, and V2O5. Incubation experiments implied that smelting ash reshaped the soil microbial community. Metagenomic binning, gene transcription, and component quantification revealed that Microbacterium sp. and Tabrizicola sp. secreted extracellular polymeric substances through epsB and yhxB gene regulation for V-NPs aggregation to alleviate toxicity under aerobic operations. The V K-edge X-ray absorption near-edge structure (XANES) spectra suggested that VO2 NPs were oxidized to V2O5 NPs. In the anaerobic case, Comamonas sp. and Achromobacter sp. reduced V(V) to V(IV) for detoxification regulated by the napA gene. This study provides a deep understanding of the V speciation in smelting ash and microbial responses, inspiring promising bioremediation strategies to reduce its negative environmental impacts.

Activation of peroxymonosulfate by natural pyrite for efficient degradation of V(IV)-citrate complex in groundwater.

The V(IV)-organic complexes are difficult to be removed from water by the traditional water treatment processes due to their strong mobility, high stability, and possible formation of V(V) with stronger toxicity during oxidation. In this study, we applied a natural iron-based ore, pyrite, to catalyze peroxymonosulfate (PMS) activation assisted with alkali precipitation to remove V(IV) containing complexes. The effects of initial V(IV)-citrate concentration, PMS concentration, ore dosage and natural anions were comprehensively investigated using citric acid as a model ligand. Results showed that pyrite can effectively purify V(IV)-citrate. Specifically, 99.4 ± 0.4% of total vanadium and 73.6 ± 0.9% of total organic carbon are removed, and the pyrite maintained high catalytic activity after multiple uses. Characterization analyses revealed that free metal ions including Fe and V(IV) ions in the solution were removed by subsequent alkali precipitation. Radical quenching experiments indicated that sulfate radical (SO4•-) and hydroxyl radical (HO•) were generated and SO4•- is the primary reactive oxygen species. This study provides an effective strategy treating V(IV)-citrate complexes in contaminated water using low-cost natural ore.

CRISPR-Cas9-Mediated Gene Therapy in Neurological Disorders.

Neurological disorders are primarily diseases with sophisticated etiology that are always refractory and recrudescent. The major obstruction to effective therapies for neurological disorders is the poor understanding of their pathogenic mechanisms. CRISPR-Cas9 technology, which allows precise and effective gene editing in almost any cell type and organism, is accelerating the pace of basic biological research. An increasing number of groups are focusing on uncovering the molecular mechanisms of neurological disorders and developing novel therapies using the CRISPR-Cas9 system. This review highlights the application of CRISPR-Cas9 technology in the treatment of neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis and/or frontotemporal dementia, Duchenne muscular dystrophy, Dravet syndrome, epilepsy, Huntington's disease, and Parkinson's disease. Hopefully, it will improve our understanding of neurological disorders and give insights into future treatments for neurological disorders.

Soil indigenous microorganisms alleviate soluble vanadium release from industrial dusts.

Vanadium-bearing dusts from industrial processes release abundant toxic vanadium, posing imminent ecological and human health concerns. Although the precipitation of these dusts has been recognized as the main source of soil vanadium pollution, little is known regarding the interrelationships between industrial dusts and soil inherent compositions. In this study, the interactions between dusts from vanadium smelting and soil indigenous microorganisms were investigated. Soluble vanadium (V) [V(V)] released from industrial dusts was reduced by 41.5 ± 0.39% with soil addition, compared to water leaching. Reducible fraction accounted for the highest proportion (55.1 ± 1.73%) of vanadium speciation in the resultant soils, while residual vanadium fraction increased to 83.7 ± 3.22% in the leached dusts. Functional genera (e.g., Aliihoeflea, Actinotalea) that transformed V(V) to insoluble vanadium (IV) alleviated dissolved vanadium release. Nitrate/nitrite reduction and glutathione metabolisms contributed to V(V) immobilization primarily. Structural equation model analysis indicated that V(V) reducers had significant negative impacts on soluble V(V) in the leachate. This first-attempt study highlights the importance of soil microorganisms in immobilizing vanadium from industrial dusts, which is helpful to develop novel strategies to reduce their environmental risks associated to vanadium smelting process.

Pancreatic stellate cells regulate branched-chain amino acid metabolism in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy: it has a 5-year survival rate of less than 9%. Although surgical resection is an effective treatment for PDAC, only a small number of patients can have their tumors surgically removed. Thus, an urgent need to find new therapeutic targets for PDAC exists. Understanding the molecular mechanism of PDAC development is essential for the treatment of this malignancy. This research aimed to study the mechanisms of pancreatic stellate cells (PSCs), which regulate branched-chain amino acid (BCAA) metabolism in PDAC. METHODS: Differentially expressed proteins were detected via nanoliquid chromatography coupled to mass spectrometry (nano-LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods were used to find the valine-leucine-isoleucine (BCAA) degradation pathway. The levels of BCAAs in the sera and tissues of patients with PDAC were measured by using nuclear magnetic resonance (NMR). The functions of BCAA concentrations and the effects of activated pancreatic stellate cells (aPSCs) were also evaluated by performing Cell Counting Kit-8, colony formation, and wound healing assays. RESULTS: A total of 1,519 proteins with significantly differential expression were discovered in PDAC and adjacent tissues by using nano-LC-MS/MS. KEGG pathway enrichment analysis identified the BCAA degradation pathway. The content of BCAA in PDAC clinical samples was up-regulated. However, the addition of different concentrations of BCAA to PDAC cell culture medium failed to promote the proliferation and migration of PDAC cells. Given that analysis based on The Cancer Genome Atlas database showed that the number of aPSCs gradually increased with the progression of PDAC, the effects of aPSCs on PDAC cells were explored. After coculture with aPSCs, PDAC cell proliferation showed a significant increase, and the proteins involved in the BCAA degradation pathway in PDAC cells had also changed. CONCLUSIONS: aPSCs could regulate BCAA metabolism to enhance the progression of PDAC, indicating that the regulation of BCAA metabolism may serve as a new therapeutic direction for PDAC.

Tip-Over Stability Analysis of a Pelvic Support Walking Robot.

Discussed in this paper is the tip-over stability analysis of a pelvic support walking robot. To improve the activities of daily living (ADL) in hemiplegic patients, a pelvic support walking robot is proposed to help patients facilitating their rehabilitation. During the gait training with the robot, the abnormal man-machine interaction forces may lead to the tip-over of the robot, which is not beneficial to the rehabilitation process. A new method is proposed to predict the possibility of tipping over and evaluate the stability of the robot based on statics model, dynamics model, and zero-moment point (ZMP) theory. Through the interaction forces and moments analysis with static case, the safe point (ZMP) is studied, and the influence factors of force/moment are analyzed by dynamics case. An optimization algorithm based on the genetic algorithm (GA) is proposed to reduce the risk of tipping over. The simulation results show that the optimization algorithm can keep the robot from tipping over when the interaction forces exceed the safety threshold.

Effects of the 1-alkyl-3-methylimidazolium bromide ionic liquids on the antioxidant defense system of Daphnia magna.

This study examined the antioxidant responses of Daphnia magna following exposure to different concentrations of the ionic liquid (IL) 1-octyl-3-methylimidazolium bromide and the 50% LC(50) concentrations of methylimidazolium bromide ILs with different alkyl-chain lengths. Activities of antioxidant defense enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase) and levels of the antioxidant glutathione and the lipid peroxidation by-product malondialdehyde were measured using traditional methods or commercial kits. The concentration and the alkyl-chain length of ILs were found to strongly influence the antioxidant system of D. magna following IL exposure, and exposure to higher IL concentrations and to ILs with longer alkyl chains generally increased the enzyme activities and biomarker levels examined. Therefore, the present study suggests that oxidative stress is involved in the mechanism of IL-induced toxicity in D. magna.

SCARNA10, a nuclear-retained long non-coding RNA, promotes liver fibrosis and serves as a potential biomarker.

Long non-coding RNAs (lncRNAs) are involved in numerous biological functions and pathological processes. However, the clinical significance of lncRNAs and their functions in liver fibrosis remain largely unclear. Methods: The transcript of lncRNA SCARNA10 in serum and liver samples from patients with advanced hepatic fibrosis, liver tissues from two fibrosis mouse models, and cultured hepatic stellate cells (HSCs) was determined by real-time RT-PCR. The effects of lentivirus-mediated knockdown or over-expression of SCARNA10 in liver fibrosis were examined in vitro and in vivo. Moreover, the effects and mechanisms of down-regulation or over-expression of SCARNA10 on the expression of the genes involved in TGFß pathway were determined. Results: It was found lncRNA ENSMUST00000158992, named as Scarna10, was remarkably up-regulated in mouse fibrotic livers according to the microarray data. We observed that the transcript of SCARNA10 was increased in the serum and liver from patients with advanced hepatic fibrosis. Furthermore, we found that SCARNA10 promoted liver fibrosis both in vitro and in vivo through inducing hepatocytes (HCs) apoptosis and HSCs activation. Mechanistically, RNA immunoprecipitation (RIP) assays demonstrated that SCARNA10 physically associated with polycomb repressive complex 2 (PRC2). Additionally, our results demonstrated that SCARNA10 functioned as a novel positive regulator of TGFß signaling in hepatic fibrogenesis by inhibiting the binding of PRC2 to the promoters of the genes associated with ECM and TGFß pathway, thus promoting the transcription of these genes. Conclusions: Our study identified a crucial role of SCARNA10 in liver fibrosis, providing a proof of this molecule as a potential diagnostic marker and a possible therapeutic target against liver fibrosis.

The analgesic effect of intravenous methylprednisolone on acute neuropathic pain with allodynia due to central cord syndrome: a retrospective study.

BACKGROUND: Central cord syndrome (CCS) may be associated with severe neuropathic pain that often resists to conventional pain therapy regimens and affects the patients' quality of life (QoL) seriously. Current treatments for CCS-associated neuropathic pain have limited evidence of efficacy. This retrospective study was performed to present the effects of early treatment with methylprednisolone (MP) on acute neuropathic pain relief and the QoL in CCS patients. PATIENTS AND METHODS: Data were collected from the medical records of CCS patients who suffered from acute neuropathic pain with allodynia. All the patients received intravenous MP treatment for up to 1 week. Patients were evaluated with standard measures of efficacy: neuropathic pain intensity, the area of allodynia, and the QoL at baseline, daily treatment, and at 1 and 3 months after the end of MP treatment. RESULTS: Thirty-four eligible patients were enrolled in our study. By the end of MP treatment, the proportion of patients who gained total or major (visual analog scale [VAS] score decreased by 50% or more) allodynia relief from the treatment was 91.18%, and a decrease in spontaneous pain was also observed. Moreover, this study showed MP could significantly improve the QoL of patients based on McGill Pain Questionnaire Short Form and EuroQol Five Dimensions Questionnaire. Four patients (11.76%) during MP treatment experienced mild or moderate side effects. None of the patients manifested CCS-associated neuropathic pain recurrence and MP-associated side effects at follow-up. CONCLUSION: The current results suggested that MP offered an effective therapeutic alternative for relieving CCS-associated acute neuropathic pain with allodynia. Given the encouraging results of this study, it would be worthwhile to confirm these results in randomized placebo-controlled clinical trials.

miR-342-3p promotes osteogenic differentiation via targeting ATF3.

Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR-342-3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR-342-3p impairs osteoblast activity and matrix mineralization, while over expression of miR-342-3p promotes osteoblast differentiation significantly. Moreover, miR-342-3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro-osteogenic differentiation-associated genes. In addition, there exists a higher frequency of methylation at the CpG island of the Enah/Vasp-Like (EVL) locus in undifferentiated pre-osteoblasts; however, demethylation of the EVL CpG island induces over expression of miR-342-3p during osteogenic differentiation. This study suggests that miR-342-3p may serves as a potential marker for diagnosis and treatment of ossification of ligament and osteoporosis.

A Transcriptome-Level Study Identifies Changing Expression Profiles for Ossification of the Ligamentum Flavum of the Spine.

Ossification of the ligamentum flavum (OLF) is a common spinal disorder that causes myelopathy and radiculopathy. Non-coding RNAs (ncRNAs) are involved in numerous pathological processes; however, very few ncRNAs have been identified to be correlated with OLF. Here we compared the expression of lncRNA, mRNA, circRNA, and microRNA in OLF tissues from OLF patients and healthy volunteers through mRNA, lncRNA, and circRNA microarrays and microRNA sequencing. A total of 2,054 mRNAs, 2,567 lncRNAs, 627 circRNAs, and 28 microRNAs (miRNAs) were altered during the process of OLF. qPCR confirmed the differential expression of selected mRNAs and ncRNAs. An lncRNA-mRNA co-expression network, miRNA-mRNA target prediction network, and competing endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA were constructed based on a correlation analysis of the differentially expressed RNA transcripts. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the differentially expressed mRNAs and the predicted miRNAs target genes were performed. In addition, a deregulated miRNA-19b-3p-based miRNA-circRNA-lncRNA-mRNA network was confirmed, by gain-of-function and loss-of-function experiments, to function in the process of ossification. Taken together, this study provides a systematic perspective on the potential function of ncRNAs in the pathogenesis of OLF.

Expression and Activity Analysis of Fructosyltransferase from Aspergillus oryzae.

The fructosyltransferase gene was isolated and cloned from Aspergillus oryzae. The gene was 1368 bp, which encoded a protein of 455 amino acids. To analyze the activity of the expressed fructosyltransferase, the pET32a-fructosyltransferase recombined plasmid was transformed into Escherichia coli BL21. The fructosyltransferase gene was successfully expressed by Isopropyl-ß-d-thiogalactoside (IPTG) induction. The molecular weight of the expression protein was about 45 kDa. The optimal conditions of protein expression were 25 °C, 0.1 mM IPTG, and 8 h of inducing time. The optimal concentration of urea dealing with inclusion body was 2.5 M. The expressed protein exhibited a strong fructosyl transfer activity. These results showed that the expressed fructosyltransferas owned transferase activity, and could catalyze the synthesis of sucrose-6-acetate.

The circular RNA ciRS-7 promotes APP and BACE1 degradation in an NF-κB-dependent manner.

The aberrant accumulation of ß-amyloid peptide (Aß) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of ß-amyloid precursor protein (APP) by ß-site APP-cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR-7 (ciRS-7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS-7, which is highly expressed in the human brain, is down-regulated in the brain of people with AD but the relevance of this finding was not clear. We have found that ciRS-7 is not involved in the regulation of APP and BACE1 gene expression, but instead reduces the protein levels of APP and BACE1 by promoting their degradation via the proteasome and lysosome. Consequently, overexpression of ciRS-7 reduces the generation of Aß, indicating a potential neuroprotective role of ciRS-7. Our data also suggest that ciRS-7 modulates APP and BACE1 levels in a nuclear factor-κB (NF-κB)-dependent manner: ciRS-7 expression inhibits translation of NF-κB and induces its cytoplasmic localization, thus derepressing expression of UCHL1, which promotes APP and BACE1 degradation. Additionally, we demonstrated that APP reduces the level of ciRS-7, revealing a mutual regulation of ciRS-7 and APP. Taken together, our data provide a molecular mechanism implicating reduced ciRS-7 expression in AD, suggesting that ciRS-7 may represent a useful target in the development of therapeutic strategies for AD.

The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFß and Notch pathways.

Long noncoding RNAs (lncRNAs) play important roles in various biological processes such as proliferation, cell death and differentiation. Here, we show that a liver-enriched lncRNA, named liver fibrosis-associated lncRNA1 (lnc-LFAR1), promotes liver fibrosis. We demonstrate that lnc-LFAR1 silencing impairs hepatic stellate cells (HSCs) activation, reduces TGFß-induced hepatocytes apoptosis in vitro and attenuates both CCl4- and bile duct ligation-induced liver fibrosis in mice. Lnc-LFAR1 promotes the binding of Smad2/3 to TGFßR1 and its phosphorylation in the cytoplasm. Lnc-LFAR1 binds directly to Smad2/3 and promotes transcription of TGFß, Smad2, Smad3, Notch2 and Notch3 which, in turn, results in TGFß and Notch pathway activation. We show that the TGFß1/Smad2/3/lnc-LFAR1 pathway provides a positive feedback loop to increase Smad2/3 response and a novel link connecting TGFß with Notch pathway. Our work identifies a liver-enriched lncRNA that regulates liver fibrogenesis and suggests it as a potential target for fibrosis treatment.Activated hepatic stellate cells are the principal contributors to liver fibrosis by secreting a variety of pro-fibrogenic cytokines . Here Zhang et al. demonstrate that a liver-enriched lncRNA, lnc-LFAR1, promotes liver fibrosis and HSC activation by activating TGFß and Notch signaling.