Outstanding Circularly Polarized TADF in Chiral Cu(I) Emitters: From Design to Application in CP-TADF OLEDs.

Low-cost molecular emitters that merge circularly polarized luminescence (CPL) and thermally activated delayed fluorescence (TADF) properties are attractive for many high-tech applications. However, the design of such emitters remains a difficult task. To address this challenge, here, we propose a simple and efficient strategy, demonstrated by the design of pseudochiral-at-metal complexes [Cu(L*)DPEPhos]PF6 bearing a (+)/(-)-menthol-derived 1,10-phenanthroline ligand (L*). These complexes exhibit a yellow CP-TADF with a record-high quantum yield (close to 100%) and high dissymmetry factor (|glum| ~ 1×10-2). Remarkably, the above compounds also show a negative thermal-quenching (NTQ) of luminescence in the 300-77 K range. Exploiting the designed Cu(I) emitters, we fabricated efficient CP-TADF OLEDs displaying mirror-imaged CPL bands with high |gEL| factors of 1.5×10-2  and the maximum EQE of 6.15%. Equally important, using the (+)-[Cu(L*)DPEPhos]PF6 complex, we have discovered that an external magnetic field noticeably suppresses CP-TADF of Cu(I) emitters. These findings are an important contribution to the CPL phenomenon and provide access to highly efficient, low-cost and robust CP-TADF emitters.

Causal relationship between modifiable risk factors and knee osteoarthritis: a Mendelian randomization study.

Background: While several risk factors for knee osteoarthritis (KOA) have been recognized, the pathogenesis of KOA and the causal relationship between modifiable risk factors and KOA in genetic epidemiology remain unclear. This study aimed to determine the causal relationship between KOA and its risk factors. Methods: Data were obtained from published Genome-Wide Association study (GWAS) databases. A two-sample Mendelian randomization (MR) analysis was performed with genetic variants associated with risk factors as instrumental variables and KOA as outcome. First, inverse variance weighting was used as the main MR analysis method, and then a series of sensitivity analyses were conducted to comprehensively evaluate the causal relationship between them. Results: Univariate forward MR analysis revealed that genetically predicted hypothyroidism, hyperthyroidism/thyrotoxicosis, educational level, income level, metabolic syndrome (MS), essential hypertension, height, hot drink temperature, diet (abstaining from sugar-sweetened or wheat products), and psychological and psychiatric disorders (stress, depression, and anxiety) were causally associated with KOA. Reverse MR exhibits a causal association between KOA and educational attainment. Multivariate MR analysis adjusted for the inclusion of potential mediators, such as body mass index (BMI), smoking, alcohol consumption, and sex, exhibited some variation in causal effects. However, hyperthyroidism/thyrotoxicosis had a significant causal effect on KOA, and there was good evidence that height, hypothyroidism, educational level, psychological and psychiatric disorders (stress, depression, and anxiety), and abstaining from wheat products had an independent causal relationship. The mediating effect of BMI as a mediator was also identified. Conclusion: This study used MR to validate the causal relationship between KOA and its risk factors, providing new insights for preventing and treating KOA in clinical practice and for developing public health policies.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

A novel approach to managing facility airborne diseases: suppressing air pathogens with smoke aerosols generated from fungicide phase transition.

BACKGROUND: Environmental microorganisms are major contributors to the development and spread of disease. Chemical disinfection can inhibit pathogens and play a preventive role against diseases. In agriculture, prolonging the floating time of chemical pesticides in the air has a positive effect on the control of airborne diseases. However, the interaction of chemical pesticides with airborne pathogens is not yet known. RESULTS: Here, triazole fungicide was transformed into stable smoke aerosols in order to assess the feasibility of employing phase transition release pesticides for air disinfection. The phase transition had a minimal impact on hexaconazole (Hexa) and myclobutanil (Mycl), with their smoke formation rates remaining consistently >90%. In microscopic morphology, triadimenol (Tria) and epoxiconazole (Epox) are solid, and tebuconazole (Tebu), Hexa, Mycl and difenoconazole (Dife) are liquid. Liquid smoke has advantages over solid smoke in the inhibition of environmental pathogens. The floatability and spatial distribution of fungicide aerosol were optimized by the combination of smoke particles with different properties, so that the fungicide aerosol could meet the conditions of practical application. In practical applications, smoke exhibits a gentler deposition process at the target interface compared to spray, along with a more homogeneous distribution of fungicides. Moreover, fungicide smoke demonstrates superior control efficacy and leaves behind lower residual amounts on fruit. CONCLUSION: In conclusion, the implementation of fungicide phase transition as a smoke aerosol offers a viable approach to effectively suppress pathogen aerosols and enhance the control of airborne diseases. © 2024 Society of Chemical Industry.

Hsa_circRNA_007630 knockdown delays colon cancer progression by modulation of ferroptosis via miR-506-3p/AURKA axis.

Colon cancer contributes to high mortality rates internationally that has seriously endangered human health. Aurora kinase A (AURKA) served as a key molecule in colon cancer. However, its role of AURKA on regulating ferroptosis in colon cancer and their possible interactions with miRNAs and circRNAs remain still elusive. Comprehensive bioinformatics analysis after RNA-sequencing was conducted to determine the differentially expressed genes (DEGs), ferroptosis-related DEGs and hub genes. The direct relationship between miR-506-3p and hsa_circRNA_007630 or AURKA was predicted, then verified by dual luciferase reporter and quantitative real-time polymerase chain reaction. The rescue experiments were conducted by cotransfection with si-hsa_circRNA_007630, miR-506-3p inhibitor or pcDNA-AURKA in HT29 cells. Erastin was used to induce ferroptosis in HT29 cells and validated by detecting levels of intracellular Fe2+, lipid reactive oxygen species, glutathione, malondialdehyde and ferroptosis markers expression. We screened a total of 331 DEGs, 26 ferroptosis-related genes, among which 3 hub genes were identified through PPI network analysis. Therein, AURKA expression was elevated in colon cancer cells. Moreover, AURKA was targeted by miR-506-3p, and hsa_circRNA_007630 operated as miR-506-3p sponge. The effect of hsa_circRNA_007630 depletion on the inhibiting malignant phenotypes of HT29 cells was rescued by inhibition of miR-506-3p or AURKA overexpression. Additionally, AURKA reduced erastin-induced ferroptosis in HT29 cells. Depletion of circRNA_007630 exerts as a suppressive role in colon cancer through a novel miR-506-3p/AURKA pathway related to ferroptosis, and might become a novel marker for colon cancer.

GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.

Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR. Seven hub genes were identified, including GABRP, FLG, ENAH, KLF4, CD24, ABLIM3 and ABLIM1, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of GABRP, FLG, KLF4, CD24, ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. In vitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR, and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.

Potential Risk Factors of Disorders of Gut-Brain Interaction in Undergraduates and Postgraduates: Partially Mediated by Life Stress and Lifestyle.

INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.

Caffeic acid mitigates myocardial fibrosis and improves heart function in post-myocardial infarction by inhibiting transforming growth factor-ß receptor 1 signaling pathways.

Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-ß receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-ß1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.

Genetic analysis of congenital unilateral renal agenesis in children based on next-generation sequencing.

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

shRNA Targeting Lentiviral Vector Minus-Strand Product Improves the Viral Titer During Viral Packaging.

Lentiviral vector (LVV) has been used as one of the common carriers for gene therapy in clinical trials. LVV-mediated clinical trials have being reported in successfully treating hundreds of ß-thalassemia cases. These LVVs bear an inversely placed ß-hemoglobin (HBB) gene expression cassette for preserving introns during the viral RNA packaging. Consequently, these LVVs often produce a small amount of negatively orientated transcript driven by its internal gene promoter and would lower the viral titer by the minus-strand complemented with the viral backbone. To overcome this problem, we designed shRNAs specifically target the minus-strand RNA driven by the LVV internal promoter that resulted in a notable increase in the viral titer. This report demonstrates a simple and positive mean for increasing the effectiveness for gene therapy with the LVV system.

Inflammatory Pathogenesis of Post-stroke Depression.

Post-stroke depression (PSD) is a complex mood disorder that emerges in individuals following a stroke, characterized by the development of depressive symptoms. The pathogensis of PSD is diverse, with inflammation playing a vital role in its onset and progression. Emerging evidence suggests that microglial activation, astrocyte responses, nuclear factor κB(NF-κB) signaling, dysregulation of the hypothalamic pituitary adrenal (HPA) axis, alterations in brain-derived neurotrophic factor (BDNF) expression, neurotransmitter imbalances, adenosine triphosphate (ATP) and its receptors and oxidative stress are intricately linked to the pathogenesis of PSD. The involvement of inflammatory cytokines in these processes highlights the significance of the inflammatory pathway. Integrating these hypotheses, the inflammatory mechanism offers a novel perspective to expand therapeutic strategies for PSD.

Reducing the transcriptional read-through rate of a lentiviral vector for ß-thalassemia gene therapy.

BACKGROUND: LentiGlobin BB305 is a self-inactivating lentiviral vector carrying a human ß-globin expressing cassette for treating ß-thalassemia. Initially, a 2 × 250 bp chicken Locus Control Region fragment of cHS4, functioning as an insulator, was placed at its ΔU3, which was removed after the first clinical trial led by a French team to avoid abnormal splicing, etc. This action could potentially lead to an increasing risk of the transcriptional read-through rate driven by the ß-globin promoter to a significant level, posing a biosafety risk in clinical trials. METHODS: In the present study, a read-through reducing agent (C-U+ or WPRE) was designed to be placed at the 3' UTR of the ß-globin gene. The Enhancer Activities and/or Transcriptional Read-Through (EATRT) rate at the mRNA level and the protein expression level regarding lentiviral preparation titer were examined. RESULTS: We found that the insertion of the element (C-U+ or WPRE) reduced the EATRT effectively by 53% or 41%, respectively. C-U+ has less impact on virus package efficiency. Furthermore, there was no significant difference in the protein expression level after the C-U+ or WPRE insertion. CONCLUSIONS: The results of the present study show that inserting C-U+ or WPRE before the polyA sequence of the BB305 would reduce the EATRT rate at no cost of its expressing efficacy and viral preparation titers. Thus, we present an alternative improvement for a safer lentiviral vector for ß-thalassemia clinical trials.

Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown. PURPOSE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI. METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF. RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-ß1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice. CONCLUSION: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

Causal association between psycho-psychological factors, such as stress, anxiety, depression, and irritable bowel syndrome: Mendelian randomization.

BACKGROUND: Pathogenesis, diagnosis, and treatment of irritable bowel syndrome (IBS) have been reported to be challenging hotspots in clinical practice. Previous observational studies have found that stress, anxiety, depression, and other mental and psychological diseases are closely associated with IBS. This study aimed to further explore the causal relationships of these associations through Mendelian randomization (MR). METHODS: The data needed for MR were obtained from publicly published genome-wide association databases. We performed a bidirectional, 2-sample MR analysis using instrumental variables (IV) associated with stress, anxiety, and depression, and other mental and psychological factors as exposures and IBS as the outcome. A reverse MR analysis with IBS as exposure and stress, anxiety, depression, and other mental and psychological factors as the outcomes was also performed. The inverse variance weighting (IVW) method was adopted as the main method of MR, and the causal effect between stress, anxiety, depression, and other mental and psychological factors and IBS was evaluated as the main result of the study. In addition, a series of sensitivity analyses was conducted to comprehensively evaluate the causal relationship between them. RESULTS: Stress, anxiety, depression, and other mental and psychological factors were the underlying etiologies for IBS (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03-1.08), and they were positively correlated. Univariate analysis further supported the above conclusions (Depression, [OR = 1.31, 95% CI: 1.05-1.63, P = .016], Anxiety, [OR = 1.53, 95% CI: 1.16-2.03, P = .003]). However, in reverse MR analysis, we found that IBS did not affect stress, anxiety, depression, or other mental and psychological factors and that there was no causal relationship between IBS and stress, anxiety, depression, or other mental and psychological factors (P > .05). CONCLUSION: This study demonstrates that mental and psychological factors are the underlying etiologies for IBS. These findings may provide important information for physicians regarding the clinical treatment of IBS.

Hirudin inhibits glioma growth through mTOR-regulated autophagy.

Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose- and time-dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3-II but not Caspase-3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell-derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3-II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin-induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy.