Visible Light-Induced Highly Regioselective and Stereoselective Oxysulfonylation of Alkynes for the Synthesis of (E)-ß-Phenoxy Vinylsulfones.

A highly efficient visible light-induced regioselective and stereoselective oxysulfonylation of alkynes with arylsulfonate phenol esters has been developed. This photocatalyst- and metal-free method proceeds smoothly under very mild conditions and exhibits a broad substrate scope, providing (E)-ß-phenoxy vinylsulfones in moderate to excellent yields. Mechanistic studies indicated the involvement of an electron donor-acceptor complex-mediated radical process.

Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: At present, studies regarding the efficacy and safety of tenecteplase for the treatment of patients with acute ischemic stroke (AIS) are still limited and inconsistent. The purpose of this systematic review and meta-analysis is to compare the efficacy and safety of tenecteplase with alteplase for the treatment of AIS patients. METHODS: Literature search was conducted in PubMed, Embase, and Cochrane Library up to May 10, 2022. Primary outcomes of this study included 90-day good outcome (defined as an mRS score of 0-2) and 90-day excellent outcome (defined as an mRS score of 0-1). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated using a random-effect model for each outcome. RESULTS: Fourteen studies with a total of 3537 patients were finally included in this meta-analysis. There was no statistical difference between patients receiving tenecteplase and those receiving alteplase in the rates of 90-day good outcome (RR 1.01; 95% CI 0.91-1.13; P = 0.79) and 90-day excellent outcome (RR 1.04; 95% CI 0.92-1.19; P = 0.50). Patients receiving tenecteplase might associated with higher incidence of early neurologic improvement compared with those receiving alteplase (RR 1.29; 95% CI 1.04-1.61; P = 0.02). In addition, no statistical difference was observed between the two groups in other outcomes. CONCLUSION: This meta-analysis indicated that tenecteplase in AIS patients is as safe and effective as alteplase and might provide more benefit than alteplase. However, due to several inherent limitations of this study, more prospective studies should be conducted to confirm the above results.

An orbital principle to design P2-NaxMO2 cathode materials for sodium-ion batteries.

Layered oxide materials are regarded to be the most promising high-performance cathode materials for sodium-ion batteries owing to their high working voltage and facile synthesis. Here, we study the influences of 3d transition metals on the cohesive energies, structural changes and operating voltages of P2-NaxMO2 during discharge based on first-principles calculations. Our results confirm that the performances of P2-NaxMO2 are associated with the chemical properties of the transition metals. In addition to this, we disclose that the involved orbitals of the 3d transition metal also greatly impact the electrochemical performance of the P2-NaxMO2 material during discharge according to the analysis of electronic structures. The jumps in the working voltage and volume during discharge are closely related to the occupation of the eg and t2g orbitals. Therefore, it is necessary to ensure that the discharge or charge process is carried out in one degenerate orbital to avoid jumps in the voltage and volume of the material. Our results could shed a light on the subsequent design of layered oxide cathodes with high cycle stability and a smooth voltage curve.

Photocatalyst and additive-free visible light induced trifluoromethylation-arylation of N-arylacrylamides with Umemoto's reagent.

A visible light induced highly convenient and practical method for the trifluoromethyl-arylation of N-arylmethacrylamides has been developed using Umemoto's reagent as the trifluoromethyl source. This user-friendly approach can proceed under visible light irradiation without any transition metal, photocatalyst and additive at room temperature. The strategy presented here provides access to trifluoromethylated oxindoles in good to excellent yields with a broad functional group tolerance. Preliminary mechanistic experiments indicated that the reaction process involves a homolytic cleavage of Umemoto's reagent irradiated by visible light.

Direct admission versus secondary transfer for acute ischemic stroke patients treated with thrombectomy: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated that mechanical thrombectomy (MT) could provide more benefit than standard medical care for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion. However, most primary stroke centers (PSCs) are unable to perform MT, and MT can only be performed in comprehensive stroke centers (CSCs) with on-site interventional neuroradiologic services. Therefore, there is an ongoing debate regarding whether patients with suspected AIS should be directly admitted to CSCs or secondarily transferred to CSCs from PSCs. This meta-analysis was aimed to investigate the two transportation paradigms of direct admission and secondary transfer, which one could provide more benefit for AIS patients treated with MT. METHODS: We conducted a systematic review and meta-analysis through searching PubMed, Embase and the Cochrane Library database up to March 2020. Primary outcomes are as follows: symptomatic intracerebral hemorrhage (sICH) within 7 days; favorable functional outcome at 3 months; mortality in hospital; mortality at 3 months; and successful recanalization rate. RESULTS: Our pooled results showed that patients directly admitted to CSCs had higher chances of achieving a favorable functional outcome at 3 months than those secondarily transferred to CSCs (OR = 1.26; 95% CI, 1.12-1.42; P < 0.001). In addition, no significant difference was found between the two transportation paradigms in the rate of sICH (OR = 0.86; 95% CI, 0.62-1.18; P = 0.35), mortality in hospital (OR = 0.84; 95% CI, 0.51-1.39; P = 0.51), mortality at 3 months (OR = 1.01; 95% CI, 0.85-1.21; P = 0.91), and successful recanalization (OR = 1.03; 95% CI, 0.88-1.20; P = 0.74). However, in the 100% bridging thrombolysis usage rate subgroup, our subgroup analysis indicated that no difference was found in any outcome between the two transportation paradigms. CONCLUSION: Patients with AIS directly admitted to CSCs for MT may be a feasible transportation paradigm for AIS patients. However, more large-scale randomized prospective trials are required to further investigate this issue.

Endovascular Thrombectomy VS. Medical Treatment for Mild Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: At present, endovascular thrombectomy (EVT) has been gradually became a standard therapy for stroke patients caused by emergent large-vessel occlusion (ELVO). However, the question about whether EVT is superior to medical treatment for mild stroke patients presenting with a low baseline National Institutes of Health Stroke Scale (NIHSS) score remains unclear. The aim of this systematic review and meta-analysis was to compare the safety and efficacy of EVT with medical treatment in mild stroke patients. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted through searching the PubMed, Embase and Cochrane Library databases. All statistical analyses were performed by using Review Manager 5.3 software. Primary outcomes of this meta-analysis were as follows: favorable functional outcome at 90 days (defined as a modified Rankin scale (mRS) score of 0-2); excellent functional outcome at 90 days (defined as a mRS score of 0-1); symptomatic intracerebral hemorrhage (sICH); mortality at 90 days. RESULTS: A total of 13 eligible studies with 2135 patients were included in this meta-analysis. The pooled results indicated that mild stroke patients underwent EVT had higher risk of sICH than those receiving medical treatment alone (OR = 3.21; 95% CI, 1.98-5.22; P < 0.001). In addition, no significant difference was found between the two groups in mortality at 90 days (OR = 1.80; 95% CI, 0.88-3.65; P=0.11). Meanwhile, no significant difference was found between the two groups in patients achieving favorable functional outcome at 90 days and excellent functional outcome at 90 days (OR = 1.10; 95% CI, 0.74-1.64; P = 0.65) (OR = 1.03; 95% CI, 0.79-1.35; P = 0.80). CONCLUSIONS: Our pooled results showed similar clinical outcomes at 90 days of EVT and medical treatment in mild stroke patients with ELVO, although patients underwent EVT had higher rates of sICH. However, due to several limitations of this meta-analysis, randomized controlled trials are needed to further evaluate the potential efficacy of EVT in mild stroke patients.

The Safety and Efficacy of Mechanical Thrombectomy in Posterior VS. Anterior Emergent Large Vessel Occlusion: A Systematic Review and Meta-analysis.

BACKGROUND AND PURPOSE: Currently, mechanical thrombectomy (MT) for emergent large-vessel occlusion (ELVO) has been widely used in the clinic. However, the question about whether MT provides the same benefits between posterior circulation emergent large vessel occlusion (pc-ELVO) and anterior emergent large vessel occlusion (ac-ELVO) remains unclear. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis of 11 studies published between 2011 and 2019 through searching the PubMed, EMBASE, and Cochrane Library. Major clinical outcomes include: (1) favorable functional outcome at 90 days; (2) symptomatic intracerebral hemorrhage (sICH); (3) mortality and; (4) successful recanalization rate. RESULTS: Eleven of 4637 studies met our pre-established inclusion criterion, comprising 4619 patients. In primary analysis, MT in patients with pc-ELVO in comparison to patients with ac-ELVO had a lower likelihood of sICH (odds ratio [OR] = .48; [95% confidence interval (CI), .26-.88]; P = .02) but a higher likelihood of mortality (OR = 1.98; [95% CI, 1.37-2.87]; P = .0003). The pooled evidence indicated that patients with pc-ELVO had worse functional outcome than patients with ac-ELVO in the large sample size group (OR = .79; [95% CI, .63-.98]; P = .03). In addition, no statistical significance was found in the outcome of successful recanalization rate (OR = 1.12; [95% CI, .88-1.42]; P = .35). CONCLUSIONS: Our results showed that patients with pc-ELVO receiving MT reduced the risk of sICH but seemed to be associated with poor prognosis.

Addition-Rearrangement of Ketenes with Lithium N- tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives.

Addition of the lithium salts of chiral N-substituted tert-butanesulfinamides to ketenes and subsequent silylation initiates stereoselective [2,3]-rearrangement, which affords enantioenriched α,α-disubstituted α-sulfenyloxy carboxamides through a reaction that faithfully transfers the absolute stereochemistry of the lithiated sulfinylamides to the α-carbon of the amide products. This addition-rearrangement can be performed together with ketene formation from acyl chloride in a single flask, providing a new and practical synthetic route to α-hydroxycarboxylic acid derivatives.

Divergent synthesis of polysubstituted cyclopropanes and ß-silyoxy imidates via switchable additions of N-tert-butanesulfinylimidates to acylsilanes.

Products derived from the reaction between N-tert-butanesulfinyl imidates and acylsilanes can be tuned by choosing appropriate bases and solvents. Here we show that in the presence of NaHMDS/THF, addition of enolized N-tert-butanesulfinyl imidates to acylsilanes and subsequent [1,2]-Brook rearrangement generate ß-silyloxy anion intermediates that undergo intramolecular cyclization to afford polysubstituted cyclopropanes. In the presence of tBuOK/toluene, the reaction generates ß-silyloxy imidates as the protonation products of the ß-silyloxy anion intermediates. Both reactions are highly diastereoselective.

Quantitative Proteomic Analysis of the Response to Cold Stress in Jojoba, a Tropical Woody Crop.

Jojoba (Simmondsia chinensis) is a semi-arid, oil-producing industrial crop that have been widely cultivated in tropical arid region. Low temperature is one of the major environmental stress that impair jojoba's growth, development and yield and limit introduction of jojoba in the vast temperate arid areas. To get insight into the molecular mechanisms of the cold stress response of jojoba, a combined physiological and quantitative proteomic analysis was conducted. Under cold stress, the photosynthesis was repressed, the level of malondialdehyde (MDA), relative electrolyte leakage (REL), soluble sugars, superoxide dismutase (SOD) and phenylalanine ammonia-lyase (PAL) were increased in jojoba leaves. Of the 2821 proteins whose abundance were determined, a total of 109 differentially accumulated proteins (DAPs) were found and quantitative real time PCR (qRT-PCR) analysis of the coding genes for 7 randomly selected DAPs were performed for validation. The identified DAPs were involved in various physiological processes. Functional classification analysis revealed that photosynthesis, adjustment of cytoskeleton and cell wall, lipid metabolism and transport, reactive oxygen species (ROS) scavenging and carbohydrate metabolism were closely associated with the cold stress response. Some cold-induced proteins, such as cold-regulated 47 (COR47), staurosporin and temperature sensitive 3-like a (STT3a), phytyl ester synthase 1 (PES1) and copper/zinc superoxide dismutase 1, might play important roles in cold acclimation in jojoba seedlings. Our work provided important data to understand the plant response to the cold stress in tropical woody crops.

Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke.

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.

Mechanical Thrombectomy for Acute Ischemic Stroke in Octogenarians: A Systematic Review and Meta-Analysis.

Background and purpose: Multiple randomized trials have confirmed that mechanical thrombectomy (MT) is an effective treatment method for patients with acute ischemic stroke (AIS). However, evidence on the safety and efficacy of MT in elderly patients compared with younger patients is controversial. This meta-analysis is aimed to systematically compare the outcomes of elderly patients and younger patients after MT for AIS. Methods: A systematic literature search was conducted through the PubMed, EMBASE, and Cochrane Library database. The primary outcomes were favorable functional outcome at 90 days and mortality. The secondary outcomes were symptomatic intracerebral hemorrhage (sICH) and successful recanalization rate. Odds ratios (ORs) were estimated using a random effects model. Results: Sixteen studies published between 2014 and 2019 were included in this meta-analysis totally involving 3,954 patients. The pooled results showed that patients aged ≥80 years had worse functional outcome (OR = 0.40; 95% CI, 0.32-0.50; P < 0.001) and higher rates of mortality (OR = 2.26; 95% CI, 1.73-2.95; P < 0.001). There was a trend of higher rates of sICH in patients aged ≥80 years compared with patients aged <80 years, whereas this did not reach statistical significance (OR = 1.28; 95% CI, 0.89-1.84; P = 0.18). Furthermore, the frequency of successful recanalization was also lower in patients aged ≥80 years compared with patients aged <80 years (OR = 0.72; 95% CI, 0.55-0.95; P = 0.02). The subgroup analysis indicated that in comparison with those studies published between 2014 and 2016, elderly patients undergoing MT had better outcomes in studies published between 2017 and 2019. Conclusion: Elderly patients undergoing MT had higher risk of mortality and worse functional outcome. Meanwhile, there was a trend toward higher rates of sICH and lower probability of achieving successful recanalization in elderly patients. These findings emphasize the need for improving the rates of successful recanalization in elderly patients with AIS. In addition, advanced technology of endovascular intervention and peri-interventional management might be associated with the prognosis in elderly patients. However, more prospective or randomized studies should be conducted to further explore this issue.

Effect of chemokine CC ligand 2 (CCL2) on α­synuclein­induced microglia proliferation and neuronal apoptosis.

The present study aimed to investigate the effect of chemokine CC ligand 2 (CCL2) on α­synuclein­mediated microglia proliferation and neuronal apoptosis. Primary cultured microglia and primary neurons were isolated and cultured in vitro. Microglia were divided into four groups: The cells in the control group were treated with an identical amount of PBS, whereas the cells in the CCL2 group were cultured in medium containing 0.05 ng/µl CCL2; cells in the α­synuclein group were treated with medium containing 0.2 ng/µl α­synuclein; and cells in the CCL2 plus α­synuclein group were cultured in medium containing 0.05 ng/µl CCL2 and 0.2 ng/µl α­synuclein. After incubation for 24 h, the proliferation of glial cells, and the level of α­synuclein in the cells, were measured. The levels of tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß) and nitric oxide (NO) in the culture medium were also measured. Levels of cleaved caspase­3, Akt and phosphorylated (p)­Akt in neurons treated with primary microglia culture medium in each group were subsequently monitored. The proliferation activity and secretion of TNF­α, IL­1ß and NO in the CCL2, α­synuclein and CCL2 plus α­synuclein groups were significantly higher compared with that in the control group (P<0.05), as were the levels of α­synuclein (P<0.01). The levels of neuronal apoptosis and cleaved caspase­3 protein in the CCL2, α­synuclein and CCL2 plus α­synuclein groups were also significantly higher compared with that in the control group (P<0.01). Taken together, these results have demonstrated that CCL2 is able to promote α­synuclein secretion and the apoptosis of neurons induced by α­synuclein, thus inducing proliferation of the microglia and secretion of TNF­α, IL­1ß and NO.

Protein phosphatase 2A regulates the p38 signaling pathway to affect the migration of astrocytes.

The aim of the present study was to investigate the effect and mechanism of protein phosphatase 2A (PP2A) on the migration of astrocytes. The primary astrocytes of neonatal mice were isolated and cultured in vitro, and treated with the PP2A activator D­erythro­sphingosine (DES) (activated group) or inhibitor okadaic acid (inhibitory group). The control group was treated with equal amounts of dimethyl sulfoxide. The activity of PP2A in the cells was detected using a commercial kit and the migration of cells was investigated using a Transwell migration assay. The protein expression of p38, phosphorylated (p)­p38, matrix metalloproteinase (MMP)­2 and MMP­9 was detected by western blotting. Cell migration and the protein expression of p38, p­p38, MMP­2 and MMP­9 was also determined following treatment of astrocytes with the p38 signaling pathway inhibitor SB202190 with or without the PP2A activator DES. The results demonstrated that the activity of PP2A in the PP2A inhibitory group was significantly decreased compared with the control group, while that of the PP2A­activated cells was significantly increased compared with the control. The protein levels of MMP­2 and MMP­9 in the PP2A inhibitory group astrocytes were significantly decreased compared with the control group, while PP2A­activated astrocytes exhibited significantly increased levels of these proteins. By contrast, the p­p38 level in PP2A inhibitory group astrocytes was significantly increased compared with the control group, while astrocytes in the activated group exhibited significantly lower levels compared with the control group. Furthermore, the cell migration ability, and MMP­2 and MMP­9 protein levels, of astrocytes that received combined treatment with SB202190 and the PP2A activator DES were significantly increased compared with the levels in astrocytes treated with SB202190 alone. The results of the current study indicate that PP2A may negatively regulate the p38 signaling pathway to promote astrocyte migration.

A Personalized QoS Prediction Approach for CPS Service Recommendation Based on Reputation and Location-Aware Collaborative Filtering.

With the rapid development of cyber-physical systems (CPS), building cyber-physical systems with high quality of service (QoS) has become an urgent requirement in both academia and industry. During the procedure of building Cyber-physical systems, it has been found that a large number of functionally equivalent services exist, so it becomes an urgent task to recommend suitable services from the large number of services available in CPS. However, since it is time-consuming, and even impractical, for a single user to invoke all of the services in CPS to experience their QoS, a robust QoS prediction method is needed to predict unknown QoS values. A commonly used method in QoS prediction is collaborative filtering, however, it is hard to deal with the data sparsity and cold start problem, and meanwhile most of the existing methods ignore the data credibility issue. Thence, in order to solve both of these challenging problems, in this paper, we design a framework of QoS prediction for CPS services, and propose a personalized QoS prediction approach based on reputation and location-aware collaborative filtering. Our approach first calculates the reputation of users by using the Dirichlet probability distribution, so as to identify untrusted users and process their unreliable data, and then it digs out the geographic neighborhood in three levels to improve the similarity calculation of users and services. Finally, the data from geographical neighbors of users and services are fused to predict the unknown QoS values. The experiments using real datasets show that our proposed approach outperforms other existing methods in terms of accuracy, efficiency, and robustness.

Construction of α-methoxyimidoyl ketonitrones via phosphite-mediated addition of α-keto N-tert-butanesulfinyl imidates to nitrosoarenes.

A dimethyl phosphite-mediated addition of α-keto N-tert-butanesulfinyl imidates to nitrosoarenes was developed. Nitrosoarenes were successfully used as electrophiles to trap aza-enolate intermediates that were generated from nucleophilic addition of deprotonated phosphite to α-keto N-tert-butanesulfinyl imidates and following phospha-Brook rearrangement, allowing efficient construction of ketonitrones with excellent (Z)-geometries.

Diastereoselective α-Hydroxylation of N-tert-Butanesulfinyl Imidates and N'-tert-Butanesulfinyl Amidines with Molecular Oxygen.

Diastereoselective α-hydroxylation using molecular oxygen has been achieved with chiral α-alkyl N-tert-butanesulfinyl imidates and α-aryl N'-tert-butanesulfinyl amidines. The aza-enolates generated from deprotonation of imidates/amidines can be intercepted by O2 with excellent diastereocontrol and subsequently transformed into α-hydroxylation products in the presence of the reductant trimethyl phosphite.

Long non-coding RNA ENST01108 promotes carcinogenesis of glioma by acting as a molecular sponge to modulate miR-489.

Gliomas are the most common primary malignant tumor in the adult central nervous system with poor prognosis. Exploring novel biomarkers and elucidating underlying molecular mechanisms to provide effective therapeutic methods is in an urgent need. Long noncoding RNAs (lncRNAs) is involved in various human diseases including cancer. However, studies on lncRNAs and gliomas are limited. In this study, we explored the expression patterns of lncRNAs in 4 pairs of glioma samples and adjacent normal tissues via microarray and chose the most up-regulated lncRNA ENST01108 (ENST01108) to further verify its oncogenic role in glioma. Clinical data suggest that ENST01108 is closely associated with the malignant status in glioma. In vitro experiment demonstrated that overexpression of ENST01108 promoted glioma cell proliferation, migration, invasion, EMT process and survival, while knockdown of ENST01108 has an opposite effect, indicating that ENST01108 serves as an oncogenic property in glioma carcinogenesis. Further, we identified miR-489 as a direct target of ENST01108 and ENST01108 negatively regulate miR-489 by act as a sponge. SIK1 is verified as the direct target of miR-489 and it is negatively regulated by miR-489. ENST01108 also positively regulate SIKI and it promotes SIKI expression by suppressing miR-489. Taken together, the reciprocal repression of ENST011081 and miR-489 may be served as potential targets for cancer therapeutics in glioma.

LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma.

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) plays important regulatory roles in many solid tumors. However, the effect of DANCR in glioma progression and underlying molecular mechanisms were not entirely explored. In the present study, we determined the expression of DANCR in glioma tissues and cell lines using qRT-PCR and further defined the biological functions. Furthermore, we used luciferase reporter assay, Western blot, and RNA immunoprecipitation (RIP) to explore the underlying mechanism. Our results showed that DANCR was significantly up-regulated in glioma tissues and cell lines (U251, U118, LN229, and U87MG). High DANCR expression was correlated with advanced tumor grade. Inhibition of DANCR suppressed the glioma cells proliferation and induced cells arrested in the G0/G1 phase. In addition, we verified that DANCR could directly interact with miR-634 in glioma cells and this interaction resulted in the inhibition of downstream of RAB1A expression. The present study demonstrated that DANCR/miR-634/RAB1A axis plays crucial roles in the progression of glioma, and DANCR might potentially serve as a therapeutic target for the treatment of glioma patients.

Long noncoding RNA ZEB1-AS1 promotes the tumorigenesis of glioma cancer cells by modulating the miR-200c/141-ZEB1 axis.

Long noncoding RNA Zinc Finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) reportedly participates in the tumorigenesis of various cancers. However, the clinical significance and biological functions of ZEB1-AS1 in glioma remain virtually unknown. Here, we show that ZEB1-AS1 expression was higher in glioma tissues and cell lines than in corresponding noncancerous samples and primary normal human astrocytes, respectively. The positive correlation of ZEB1-AS1 expression with the poor prognosis and progressive histological stages of glioma patients was clinically proven. In vitro assays revealed that silencing ZEB1-AS1 inhibited glioma cancer-cell growth and motility. Xenograft experiments confirmed that ZEB1-AS1 depletion attenuated tumor growth and metastasis. Dual-luciferase report assay showed that ZEB1-AS1 directly regulated microRNA-200c/141 (miR-200c/141) in glioma cells, which was confirmed by RNA immunoprecipitation assay. Furthermore, the inhibition of miR-200c/141 partially balanced the inhibition effects of cell proliferation and motility induced by ZEB1-AS1 depletion on U87 cells. Additionally, ZEB1-AS1 can regulate ZEB1 through miR-200c/141. Hence, ZEB1-AS1 directly regulated miR-200c/141 in glioma cells and relieved the inhibition of ZEB1 caused by miR-200c/141. Overall, this study revealed a novel regulatory mechanism between ZEB1-AS1 and the miR-200c/141-ZEB1 axis. The interaction between ZEB1-AS1 and miR-200c/141-ZEB1 axis was involved in the progression of glioma cells. Therefore, targeting this interaction was a promising strategy for glioma treatment.