Ginsenoside Rg3 exhibits anti-catabolic and anti-apoptotic effects in IL-1ß treated human disc nucleus pulposus cells and in a rat model of disc degeneration by inactivating the MAPK pathway.

Intervertebral disc degeneration (IDD) is the major cause of degeneration of joint diseases. IDD is characterized by a large number of apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Ginsenoside Rg3 is the active component extracted from ginseng and has a vital function in modulating diseases. This study aimed to investigate the regulatory functions of ginsenoside Rg3 in IDD. We established the IDD cell model via inducing NPCs with IL-1ß. The rat model of IDD was established by fibrous ring puncture method. Cell apoptotic capability was assessed through TUNEL assay. The levels of catabolic proteases MMPs and ADAMTSs were tested by western blot and RT-qPCR. IL-1ß induction notably promoted the apoptosis of NPCs, while ginsenoside Rg3 treatment reversed the promoting function of IL-1ß. Furthermore, we found that MMP2, MMP3, Adamts4, and Adamts5 levels were increased in IL-1ß-induced NPCs, while ginsenoside Rg3 treatment markedly reduced their levels. Additionally, ginsenoside Rg3 was found to suppress the IL-1ß-stimulated p38 MAPK pathway in NPCs. In the IDD rat model, we found that ginsenoside Rg3 treatment can alleviate NPC degeneration, recover the arrangement of annulus fibrous, and preserve more proteoglycan matrix. Moreover, ginsenoside Rg3 reduced apoptosis and catabolism and inactivated the p38 MAPK pathway in IDD rats. Ginsenoside Rg3 exhibits anti-catabolic and anti-apoptotic effects in IL-1ß-stimulated NPCs and IDD rats by inactivating MAPK pathway.

A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

Mediating effects of social support, mental health between stress overload, fatigue and turnover intention among operating theatre nurses.

BACKGROUND: The high rate of nurses turnover and nursing staff shortage have been an ongoing concern issue and a challenge for global health systems. To explore the turnover intention among operating theatre nurses, and to test the hypothetical model for estimating the effects of stress overload and fatigue between social support, mental health and turnover intention. DESIGN: a multi-center and cross-sectional online survey. METHODS: This study was conducted from October 2020 to March 2021 comprised 1060 operating theatre nurses from 76 Chinese hospitals. The descriptive analysis, independent sample t test and one-way analysis of variance and Spearman correlation analysis were used to explore the relationships among variables by the SPSS software, and stepwise multiple linear regression analysis was utilized to identify influencing factors of turnover intention and its dimensions among operating theatre nurses. A structural equation model was analyzed by the AMOS software. RESULTS: Social support, mental health, stress overload and fatigue were important predictors of turnover intention among operating theatre nurses. Besides, stress overload positively affected fatigue, mental health and turnover intention; fatigue negatively affected social support, however, fatigue positively affected mental health; social support negatively affected mental health and turnover intention; mental health positively affected turnover intention. Moreover, social support, mental health mediated between stress overload, fatigue and turnover intention among operating theatre nurses. CONCLUSION: Social support, mental health mediated between stress overload, fatigue and turnover intention among operating theatre nurses.

Clofazimine: A journey of a drug.

Among different strategies to develop novel therapies, drug repositioning (aka repurposing) aims at identifying new uses of an already approved or investigational drug. This approach has the advantages of availability of the extensive pre-existing knowledge of the drug's safety, pharmacology and toxicology, manufacturing and formulation. It provides advantages to the risk-versus-rewards trade-off as compared to the costly and time-consuming de novo drug discovery process. Clofazimine, a red-colored synthetic derivative of riminophenazines initially isolated from lichens, was first synthesized in the 1950 s, and passed through several phases of repositioning in its history as a drug. Being initially developed as an anti-tuberculosis treatment, it was repurposed for the treatment of leprosy, prior to re-repositioning for the treatment of multidrug-resistant tuberculosis and other infections. Since 1990 s, reports on the anticancer properties of clofazimine, both in vitro and in vivo, started to appear. Among the diverse mechanisms of action proposed, the activity of clofazimine as a specific inhibitor of the oncogenic Wnt signaling pathway has recently emerged as the promising targeting mechanism of the drug against breast, colon, liver, and other forms of cancer. Seventy years after the initial discovery, clofazimine's journey as a drug finding new applications continues, serving as a colorful illustration of drug repurposing in modern pharmacology.

Atomically Dispersed Mg-N-C Material Supported Highly Crystalline Pt3Mg Nanoalloys for Efficient Oxygen Reduction Reaction.

Single-atom or atomically dispersed metal materials have emerged as highly efficient catalysts, but their potential as excellent supports has rarely been reported. In this work, we prepared Mg-N-C materials derived from annealing of a Mg-based metal-organic framework (MOF). By introducing Pt, Mg-N-C not only serves as a platform for anchoring Pt nanoparticles but also facilitates the integration of Mg into the Pt face-centered cubic lattice, resulting in the formation of highly crystalline Pt3Mg nanoalloys via the metal-support interfacial interaction. Synchrotron radiation-based X-ray absorption spectroscopy (XAS) enables us to study the interfacial interaction and the surface electronic structure of this intricate system. The formation of Pt3Mg nanoalloys induces a downshift of the Pt d-band (gaining d-charge), as revealed by the decrease in the Pt L3-edge white-line (WL) area under the curve. This downshift can weaken the binding of oxygen reduction reaction (ORR) intermediates, hence improving the ORR performance.

Janus particle-engineered structural lipiodol droplets for arterial embolization.

Embolization (utilizing embolic materials to block blood vessels) has been considered one of the most promising strategies for clinical disease treatments. However, the existing embolic materials have poor embolization effectiveness, posing a great challenge to highly efficient embolization. In this study, we construct Janus particle-engineered structural lipiodol droplets by programming the self-assembly of Janus particles at the lipiodol-water interface. As a result, we achieve highly efficient renal embolization in rabbits. The obtained structural lipiodol droplets exhibit excellent mechanical stability and viscoelasticity, enabling them to closely pack together to efficiently embolize the feeding artery. They also feature good viscoelastic deformation capacities and can travel distally to embolize finer vasculatures down to 40 µm. After 14 days post-embolization, the Janus particle-engineered structural lipiodol droplets achieve efficient embolization without evidence of recanalization or non-target embolization, exhibiting embolization effectiveness superior to the clinical lipiodol-based emulsion. Our strategy provides an alternative approach to large-scale fabricate embolic materials for highly efficient embolization and exhibits good potential for clinical applications.

High Valence State Sites as Favorable Reductive Centers for High-Current-Density Water Splitting.

Electrochemical water splitting is a promising approach for producing sustainable and clean hydrogen. Typically, high valence state sites are favorable for oxidation evolution reaction (OER), while low valence states can facilitate hydrogen evolution reaction (HER). However, here we proposed a high valence state of Co3+ in Ni9.5 Co0.5 -S-FeOx hybrid as the favorable center for efficient and stable HER, while structural analogues with low chemical states showed much worse performance. As a result, the Ni9.5 Co0.5 -S-FeOx catalyst could drive alkaline HER with an ultra-low overpotential of 22 mV for 10 mA cm-2 , and 175 mV for 1000 mA cm-2 at the industrial temperature of 60 °C, with an excellent stability over 300 h. Moreover, this material could work for both OER and HER, with a low cell voltage being 1.730 V to achieve 1000 mA cm-2 for overall water splitting at 60 °C. X-ray absorption spectroscopy (XAS) clearly identified the high valence Co3+ sites, while in situ XAS during HER and theoretical calculations revealed the favorable electron capture at Co3+ and suitable H adsorption/desorption energy around Co3+ , which could accelerate the HER. The understanding of high valence states to drive reductive reactions may pave the way for the rational design of energy-related catalysts.

Effects of intra-aortic balloon pump on in-hospital outcomes and 1-year mortality in patients with acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: The role of intra-aortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction (AMI) is still a subject of intense debate. In this study, we aim to investigate the effect of IABP on the clinical outcomes of patients with AMI complicated by cardiogenic shock undergoing percutaneous coronary intervention (PCI). METHODS: From the Medical Information Mart for Intensive Care (MIMIC)-IV 2.2, 6017 AMI patients were subtracted, and 250 patients with AMI complicated by cardiogenic shock undergoing PCI were analyzed. In-hospital outcomes (death, 24-hour urine volumes, length of ICU stays, and length of hospital stays) and 1-year mortality were compared between IABP and control during the hospital course and 12-month follow-up. RESULTS: An IABP was implanted in 30.8% (77/250) of patients with infarct-related cardiogenic shock undergoing PCI. IABP patients had higher levels of Troponin T (3.94 [0.73-11.85] ng/ml vs. 1.99 [0.55-5.75] ng/ml, p-value = 0.02). IABP patients have a longer length of ICU and hospital stays (124 [63-212] hours vs. 83 [43-163] hours, p-value = 0.005; 250 [128-435] hours vs. 170 [86-294] hours, p-value = 0.009). IABP use was not associated with lower in-hospital mortality (33.8% vs. 33.0%, p-value = 0.90) and increased 24-hour urine volumes (2100 [1455-3208] ml vs. 1915 [1110-2815] ml, p-value = 0.25). In addition, 1-year mortality was not different between the IABP and the control group (48.1% vs. 48.0%; hazard ratio 1.04, 95% CI 0.70-1.54, p-value = 0.851). CONCLUSION: IABP may be associated with longer ICU and hospital stays but not better short-and long-term clinical prognosis.

Construction and Validation of the Postgraduate Research Innovation Ability Scale (PRIAS): A Three-Dimensional Structural Model Based on Componential Theory of Creativity.

Purpose: To explore the structure of postgraduate research innovation ability and verify the Postgraduate Research Innovation Ability Scale. Patients and Methods: This study was based on the componential theory of creativity. First, we drafted an item pool from the literature review, semi-structured interviews, and group discussions. A total of 125 postgraduates were selected for the pre-test. After item selection and exploratory factor analysis, an 11-item, 3-factor postgraduate research innovation ability scale was formed. The scale was applied to a sample of 330 postgraduates from various domestic universities. Exploratory factor analysis and confirmatory factor analysis were used to examine the factor structure of the scales. Results: The results support a three-factor model including creativity-relevant processes, domain-relevant skills, and intrinsic motivation for the Postgraduate Research Innovation Ability Scale. The scale showed good internal consistency (α =0.89) and test-retest reliability (r=0.86). Exploratory factor analysis showed that the KMO value was 0.87, and the Bartlett's sphericity test results were significant. Confirmatory factor analysis confirmed that the three-factor construct demonstrated a good model fit (χ2/df=1.945, GFI=0.916, CFI=0.950, RMSEA=0.076). Conclusion: The Postgraduate Research Innovation Ability Scale has good reliability and validity, and it can be used for future research in related fields.

Thermoresponsive hydrogel for transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the most commonly used treatments for hepatocellular carcinoma (HCC); however, the poor stability of emulsified chemotherapy drugs by iodinated oil always leads to serious systemic cytotoxicity. Herein, a composite hydrogel Epi/Etpoil@MC/XG was proposed by stably distributing ethiodized poppyseed oil (Etpoil) and epirubicin (Epi) in the blend hydrogel of methylcellulose (MC) and xanthan gum (XG). Benefiting from its adjusted thermo-responsive and injectable properties, the Epi/Etpoil@MC/XG has been successfully applied in the embolization of the feeding artery for a VX2 tumor model.

Wnt-Independent SARS-CoV-2 Infection in Pulmonary Epithelial Cells.

The Wnt signaling pathway within host cells regulates infections by several pathogenic bacteria and viruses. Recent studies suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on ß-catenin and can be inhibited by the antileprotic drug clofazimine. Since clofazimine has been identified by us as a specific inhibitor of Wnt/ß-catenin signaling, these works could indicate a potential role of the Wnt pathway in SARS-CoV-2 infection. Here, we show that the Wnt pathway is active in pulmonary epithelial cells. However, we find that in multiple assays, SARS-CoV-2 infection is insensitive to Wnt inhibitors, including clofazimine, acting at different levels within the pathway. Our findings assert that endogenous Wnt signaling in the lung is unlikely required or involved in the SARS-CoV-2 infection and that pharmacological inhibition of this pathway with clofazimine or other compounds is not a universal way to develop treatments against the SARS-CoV-2 infection. IMPORTANCE The development of inhibitors of the SARS-CoV-2 infection remains a need of utmost importance. The Wnt signaling pathway in host cells is often implicated in infections by bacteria and viruses. In this work, we show that, despite previous indications, pharmacological modulation of the Wnt pathway does not represent a promising strategy to control SARS-CoV-2 infection in lung epithelia.

CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T-cell response. Moreover, the nanovaccine Hy-M-Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy-M-Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.

Expression and prognostic signatures of m6A-related lncRNAs in hepatocellular carcinoma.

BACKGROUND: N6-methyladenosine (m6A) is a common modification and plays an important role in various biological processes, but m6A-related lncRNA functions in hepatocellular carcinoma (HCC) have not been systematically clarified. METHODS: The clinical data and RNA-seq transcriptome of 375 cases of HCC and 50 cases of normal tissues were obtained from the Cancer Gene Atlas database. Co-expression analysis was used to obtain m6A-related lncRNA. The independent prognostic factors were identified by univariate and multivariate Cox regression models. Kaplan-Meier method was used in survival analysis. The core gene of the mRNA-mRNA interaction network is related to m6A-related lncRNAs obtained by the CytoHubba plugin of Cytoscape. Gene ontology and Kyoto Gene Encyclopedia were analyzed to find out the potential mechanism. CIBERSORT algorithm was used to calculate the relative proportion of immune infiltrating cells. RESULTS: We identified two subgroups (cluster 1 and cluster 2) according to the expression level. The survival analysis curve and receiver operating characteristic curve proved that this model could predict the prognosis of HCC patients. The univariate and multivariate Cox regression analyses showed the independent prognostic value. UBE2C was screened as the pivotal gene. The expression level of m6A-related lncRNAs causes changes in the tumor immune microenvironment. CONCLUSION: The expression levels of m6A-related lncRNAs were significantly different and the prognostic value of m6A-related lncRNAs was confirmed. The m6A-related lncRNAs are expected to be prognostic signatures in HCC.

"Forced Transformation" or "Regulation Capture"-Research on the Interactive Mechanism between Environmental Regulation and Green Transformation of Dairy Farming Subject Production.

Under the situation of an increasing resource and environment shortage, the green transformation of dairy farming subject production driven by environmental regulation is the concentrated embodiment of a "promising government" to solve the problem of breeding environmental pollution. Due to the shortcomings of environmental regulation itself and the undefined connotation of the green transformation of dairy farming subject production, the interactive relationship between the two remains unclear at present. Based on defining the concept of green transformation of dairy farming subject production, this paper aims to analyze the interactive mechanism between the environmental regulation and green transformation of dairy farming main production, build a dynamic game model between the environmental regulators and dairy farming subject, and introduce the constraints and benefits of a reputation mechanism on the behavior in the model to explore whether environmental regulation can drive the green transformation of dairy farming subject production. The results showed that the green transformation of dairy farming subject production followed the "subject substitution view" and emphasized "source reduction, process control and terminal treatment". Strictly designed environmental regulations could effectively drive the green transformation of dairy farming subject production, but it was inevitable that the environmental regulators were vulnerable to the rent-seeking behavior of dairy farming subjects, which was "regulation capture". The introduction of the reputation mechanism has greatly improved the rent-seeking behavior of dairy farming subjects and the probability that environmental regulators have "regulation capture", indirectly forcing dairy farming subjects to participate in the green transformation of production. The greater the punishment for dairy farming subjects who do not participate in the green transformation of production was, the more they can be forced to participate in the green transformation of production. At the same time, it also reduces the risk of damage to the credibility of the government. Based on the studies above, this paper also further discussed the shortcomings of environmental regulation itself, including the "re exit and light implementation" of the environmental regulation policy, "decentralization and light inspection" of the environmental regulation subject, "result and light process" of the environmental regulation mode, and "formal regulation and light informal regulation" of the environmental regulation form, which provides a scientific reference for the formulation of the environmental regulation policy of livestock and poultry breeding in the future. Compared with previous studies, this paper is innovative in two aspects: first, it defines the conceptual connotation of a green transformation of dairy farming subject production, and second, it systematically discusses the interaction mechanism between the environmental regulation and green transformation of dairy farming subject production. This paper provides a scientific reference for the development of future environmental regulation policies for livestock and poultry farming.

Acute myocardial infarction occurring after hypertrophic obstructive cardiomyopathy with paroxysmal atrial fibrillation: a case report.

Atheromatous plaque rupture and coronary artery stenosis/occlusion are leading causes of acute myocardial infarction (AMI). Other reasons for AMI are frequently overlooked. We report a rare case of AMI occurring after hypertrophic obstructive cardiomyopathy with paroxysmal atrial fibrillation. Although the patient showed multiple lead ST-T changes on an electrocardiogram and elevated circulating cardiac troponin I concentrations, no stenotic lesions were observed by repeated invasive coronary angiography examinations. Hypertrophic obstructive cardiomyopathy with paroxysmal atrial fibrillation was suspected as the primary cause of AMI. The patient received radiofrequency catheter ablation therapy and was free of atrial fibrillation and myocardial infarction 1 year postoperatively. The clinical management and outcome of the patient are also discussed.

Effect of active and passive warming on preventing hypothermia and shivering during cesarean delivery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Perioperative hypothermia and shivering commonly occur in pregnant women undergoing cesarean section. The warming method is usually used to prevent hypothermia and shivering. However, the effect of active warming (AW) prior to passive warming (PW) on the perioperative outcomes of pregnant women and their offspring remains controversial. METHODS: This study aimed to investigate the effects of AW and PW on maternal and newborn perioperative outcomes during cesarean delivery. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PubMed, Embase, Scopus, and the Cochrane Library were used to search for randomized controlled trials (RCTs) up to August 7, 2022. The Cochrane risk of bias assessment tool was used to assess articles selected for the systematic review. Continuous data were analyzed using weighted mean differences (WMDs) with 95% confidence intervals (CIs), and categorical data were analyzed by the random-effects model. RESULTS: A total of 1241 participants from twelve RCTs were selected for the final meta-analysis. AW was associated with a lower risk of maternal hypothermia (RR: 0.77, 95% CI: 0.63-0.93, P = 0.007) and shivering (RR: 0.56, 95% CI: 0.37-0.85; P = 0.007). AW was associated with high maternal temperature (WMD: 0.27, 95%CI: 0.14 to 0.40, P < 0.001). No significant difference was observed between AW and PW in terms of hypothermia (RR: 0.60, 95% CI: 0.24-1.51, P = 0.278), temperature (WMD: 0.31, 95% CI: - 0.00 to 0.62; P = 0.050), and umbilical vein PH in newborns (WMD: -0.00; 95% CI: - 0.02 to 0.02, P = 0.710). CONCLUSIONS: These findings suggested that AW can better prevent maternal hypothermia and shivering than PW. In contrast, no significant effect was observed in newborns. Overall, the quality of the included studies is high due to RCTs, low risk of bias, consistency, and precision. We identified the quality of the overall evidence from the survey to be GRADE I.

The relationship between negative peer relationship and non-suicidal self-injury in Chinese adolescents: A moderated-mediation model.

Objective: The objective of the study was to investigate the mediating effect of regulatory emotional self-efficacy (RESE) between negative peer relationship and non-suicidal self-injury (NSSI), as well as the moderating effect of gender difference. Methods: A study of 578 Chinese adolescents (46.9% males, mean age = 16.32 years, SD =0.54) was conducted using the Child and Adolescent Peer Relationship Inventory, Regulatory Emotional Self-Efficacy Scale, and the Adolescent Self-Injury Questionnaire. Results: Negative peer relationship was positively correlated with NSSI, and RESE was negatively correlated with negative peer relationship and NSSI. RESE mediated the association between negative peer relationship and NSSI. The first stage(predicting the effect of negative peer relationship on RESE) and the second stage (predicting the effect of RESE on NSSI) of the mediation effect of RESE were both moderated by gender. Specifically, compared with boys, the effect of negative peer relationship on RESE was stronger for girls, and the effect of RESE on NSSI was stronger for girls than boys. Conclusion: Negative peer relationships may influence NSSI of adolescents through the mediating effect of RESE and the moderating role of gender.

Positively Charged Pt-Based Nanoreactor for Efficient and Stable Hydrogen Evolution.

Positively charged Pt can work as the active center for hydrogen evolution reaction (HER) but the corresponding design of state-of-the-art electrocatalysts at high current densities has never been realized. Here the application of positively charged Pt in an effective Fe-PtNiPO nanoreactor for highly efficient and stable HER is demonstrated. Synchrotron radiation X-ray absorption spectroscopy confirms the formation of internal positively charged Pt and the in situ experiments reveal the quick charge transfer in the nanoreactor. Ni-based materials around Pt are used to tune the electronic structure and promote the water dissociation to form locally enriched H+ , while a porous Fe shell can both prevent the loss of active material and allow the efficient material transport. All the beneficial compositions work together to form an effective nanoreactor for HER. As a result, the Fe-PtNiPO nanoreactor shows a low overpotential of 19 mV to achieve 10 mA cm-2 and exhibits a high mass activity of 10.93 A mgPt -1 (at 100 mV). Most importantly, it only needs an ultra-low overpotential of 193 mV to achieve a high current density of 1000 mA cm-2 with an excellent stability over 300 h, which represents one of the best electrocatalysts for alkaline HER and might be used for large-scale industrial application in the future.

Tumor-Derived Membrane Vesicles: A Promising Tool for Personalized Immunotherapy.

Tumor-derived membrane vesicles (TDMVs) are non-invasive, chemotactic, easily obtained characteristics and contain various tumor-borne substances, such as nucleic acid and proteins. The unique properties of tumor cells and membranes make them widely used in drug loading, membrane fusion and vaccines. In particular, personalized vectors prepared using the editable properties of cells can help in the design of personalized vaccines. This review focuses on recent research on TDMV technology and its application in personalized immunotherapy. We elucidate the strengths and challenges of TDMVs to promote their application from theory to clinical practice.

Long noncoding RNA TFAP2A AS1 exerts promotive effects in non small cell lung cancer progression via controlling the microRNA 548a 3p/CDK4 axis.

In this study, we mainly focus on probing expression profile and detailed functions of long non coding RNA TFAP2A antisense RNA 1 (TFAP2A AS1) in non small cell lung cancer (NSCLC). Moreover, the mechanisms played by TFAP2A AS1 were unraveled comprehensively. Herein, a notable overexpressed TFAP2A AS1 in NSCLC was observed by TCGA and our own cohort. An increased TFAP2A AS1 level displayed a negative correlation with the overall survival of patients with NSCLC. Loss of function approaches illustrated that the absence of TFAP2A AS1 weakened NSCLC cell proliferation, colony formation, migration and invasion in vitro. Also, interference of TFAP2A AS1 caused in vivo tumor growth suppression. Mechanistically, TFAP2A AS1 could negative regulate microRNA 584 3p (miR 584 3p) as a competitive endogenous RNA. Furthermore, cyclin dependent kinase 4 (CDK4), a direct target of miR 584 3p, was positively controlled by TFAP2A AS1 in a miR 5184 3p dependent manner. Rescue function experiments corroborated that the anticancer activities of TFAP2A AS1 deficient on the oncogenicity of NSCLC cells were reversed by downregulating miR 584 3p or overexpressing CDK4. To sum up, TFAP2A AS1 exhibits cancer promoting roles in NSCLC through the adjustment of miR 584 3p/CDK4 axis.