Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.

Facile Generation of Neutralizing Antibodies on Tyrosine Phosphorylated IRS1 by Epitope-Directed Elicitation.

Generating antibodies specific to the functional epitope containing phosphotyrosine remains highly challenging. Here, we create an "epitope-directed immunogen" by incorporating fluorosulfate-l-tyrosine (FSY) with cross-linking activities into a specific tyrosine phosphorylation site of insulin receptor substrate 1 (IRS1) and immunizing mice to elicit site-specific antibody responses. By taking advantage of antibody clonal selection and evolution in vivo, we efficiently identified antibodies that target the IRS1 Y612 epitope and are capable of neutralizing the binding interactions between IRS1 and p85α mediated by the phosphorylation of Y612. This epitope-directed antibody elicitation by encoding the cross-linking reactivity in the immunogen potentially enables a general method for facile generation of neutralizing antibodies to protein tyrosine phosphorylation sites.

PCAF-mediated acetylation of METTL3 impairs mRNA translation efficiency in response to oxidative stress.

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity. METTL3 enhances RNA translation independently of its catalytic activity. However, the underlying mechanism is still elusive. Here, we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3. Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177. Importantly, acetylation of METTL3 blocks its interaction with EIF3H, a subunit of the translation initiation factor, thereby reducing mRNA translation efficiency. Interestingly, acetylation of METTL3 responds to oxidative stress. Mechanistically, oxidative stress enhances the interaction of PCAF with METTL3, increases METTL3 acetylation, and suppresses the interaction of METTL3 with EIF3H, thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation. Altogether, we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

Enhanced NOx reduction on CePO4 catalysts: Cu-loading, phosphotungstic acid, and insights from In-situ DRIFTs and DFT.

This study investigates the effects of varying Cu/Ce doping ratios on the NH3-SCR denitrification efficiency using Cu-HPW/CePO4 catalysts, where CePO4 serves as the support and copper-doped phosphotungstic acid (HPW) acts as the active phase. The NH3-SCR reaction mechanism was studied by In-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (In-situ DRIFTs) and Density Functional Theory (DFT). In-situ DRIFTs were employed to delve into the intricacies of adsorption and transformation dynamics at the surface sites of catalysts. This approach furnished a robust theoretical foundation aimed at augmenting the efficacy of low-temperature denitrification catalysts. DFT calculations were used to systematically investigate the reaction pathways, intermediates, transition states, and energy barriers over the HPW structure model to complete the NH3-SCR reaction. Empirical evidence suggests that modifying the catalysts with copper substantially enhances their denitrification efficacy and extends their operational temperature spectrum. A notable initial increase in denitrification efficiency was observed with increasing levels of copper modification, followed by a decline. Within the HPW-O15H site, the NH3-SCR reaction advances through both the E-R and L-H mechanisms, encompassing processes such as NH3 adsorption, intermediate formation and transformation, and product release.

The role of ACE2 in RAS axis on microglia activation in Parkinson's disease.

BACKGROUND: The classic renin-angiotensin system (RAS) induces organ damage, while the ACE2/Ang-(1-7)/MasR axis opposes it. However, the role of ACE2 in the brain is unclear. We studied ACE2's role in the brain. METHOD: We used male C57BL/6J (WT) mice, ACE2 knockout (KO) mice, and MPTP-induced mice. Behavioral tests confirmed successful modeling. We assessed the impact of ACE2 KO on the RAS axis and PD index, including ACE, ACE2, AT1, AT2, MasR, TH, α-syn, and Iba1. We investigated ACE2 and MasR's involvement in microglial activation via western blot and immunofluorescence. GSE10867 and GSE26532 datasets were used to analyze the effects of AT1 antagonists and in vitro PD models on microglia. RESULT: Behavioral tests revealed that MPTP mice displayed motor deficits, depression, anxiety, and increased inflammatory markers in the SN and CPU, with reduced antioxidant capacity. ACE2 KO worsened these symptoms and exacerbated inflammation and oxidative stress. LPS-induced ACE2/MasR activation in BV2 cells demonstrated anti-inflammatory and neuroprotective effects by modulating microglial polarization. Antagonists inhibited microglial activation via inflammation and ROS processes. CONCLUSION: The RAS axis regulates inflammation and oxidative stress to maintain CNS function, suggesting potential targets for neurologic disease treatment. Understanding microglial RAS activation can offer new therapeutic strategies.

A Survey on Open-Vocabulary Detection and Segmentation: Past, Present, and Future.

As the most fundamental scene understanding tasks, object detection and segmentation have made tremendous progress in deep learning era. Due to the expensive manual labeling cost, the annotated categories in existing datasets are often small-scale and pre-defined, i.e., state-of-the-art fully-supervised detectors and segmentors fail to generalize beyond the closed vocabulary. To resolve this limitation, in the last few years, the community has witnessed an increasing attention toward Open-Vocabulary Detection (OVD) and Segmentation (OVS). By "open-vocabulary", we mean that the models can classify objects beyond pre-defined categories. In this survey, we provide a comprehensive review on recent developments of OVD and OVS. A taxonomy is first developed to organize different tasks and methodologies. We find that the permission and usage of weak supervision signals can well discriminate different methodologies, including: visual-semantic space mapping, novel visual feature synthesis, region-aware training, pseudo-labeling, knowledge distillation, and transfer learning. The proposed taxonomy is universal across different tasks, covering object detection, semantic/instance/panoptic segmentation, 3D and video understanding. The main design principles, key challenges, development routes, methodology strengths, and weaknesses are thoroughly analyzed. In addition, we benchmark each task along with the vital components of each method in appendix and updated online at awesome-ovd-ovs. Finally, several promising directions are provided and discussed to stimulate future research.

Towards a Green Equal City: Measuring and matching the supply-demand of green exposure in urban center.

Exposure to green environments is crucial for human health. However, urbanization has reduced the contact of urban residents with natural environments, causing a mismatch between the supply and demand for green exposure. Research in this field is hindered by the lack of long-term, reliable data sources and methodologies, leading to insufficient consideration of temporal variations in green exposure. This study presented a comprehensive methodology for assessing green exposure at a fine scale utilizing satellite images for urban tree canopy identification. We conducted a case study in the core area of Beijing from 2010 to 2020 and examined the effects of urban renewal and alleviation efforts. The results revealed a slight decrease in green exposure for the elderly over the decade, with minimal changes in equity. In contrast, green exposure for children has increased, with increasing inequality. Moreover, urban renewal has improved green exposure for nearly half of the low-supply blocks. However, a significant mismatch was observed between supply and demand for blocks with increased demand but limited supply. This study enhances the assessment of green exposure and provides guidance for planning and constructing a "Green Equal City".

An Efficient Privacy Protection Mechanism for Blockchain-Based Federated Learning System in UAV-MEC Networks.

The widespread use of UAVs in smart cities for tasks like traffic monitoring and environmental data collection creates significant privacy and security concerns due to the transmission of sensitive data. Traditional UAV-MEC systems with centralized data processing expose this data to risks like breaches and manipulation, potentially hindering the adoption of these valuable technologies. To address this critical challenge, we propose UBFL, a novel privacy-preserving federated learning mechanism that integrates blockchain technology for secure and efficient data sharing. Unlike traditional methods relying on differential privacy (DP), UBFL employs an adaptive nonlinear encryption function to safeguard the privacy of UAV model updates while maintaining data integrity and accuracy. This innovative approach enables rapid convergence, allowing the base station to efficiently identify and filter out severely compromised UAVs attempting to inject malicious data. Additionally, UBFL incorporates the Random Cut Forest (RCF) anomaly detection algorithm to actively identify and mitigate poisoning data attacks. Extensive comparative experiments on benchmark datasets CIFAR10 and Mnist demonstrably showcase UBFL's effectiveness. Compared to DP-based methods, UBFL achieves accuracy (99.98%), precision (99.93%), recall (99.92%), and F-Score (99.92%) in privacy preservation while maintaining superior accuracy. Notably, under data pollution scenarios with varying attack sample rates (10%, 20%, and 30%), UBFL exhibits exceptional resilience, highlighting its robust capabilities in securing UAV gradients within MEC environments.

A fast response time gas ionization chamber detector with a grid structure.

The time response characteristic of the detector is crucial in radiation imaging systems. Unfortunately, existing parallel plate ionization chamber detectors have a slow response time, which leads to blurry radiation images. To enhance imaging quality, the electrode structure of the detector must be modified to reduce the response time. This paper proposes a gas detector with a grid structure that has a fast response time. In this study, the detector electrostatic field was calculated using COMSOL, while Garfield++ was utilized to simulate the detector's output signal. To validate the accuracy of simulation results, the experimental ionization chamber was tested on the experimental platform. The results revealed that the average electric field intensity in the induced region of the grid detector was increased by at least 33%. The detector response time was reduced to 27% -38% of that of the parallel plate detector, while the sensitivity of the detector was only reduced by 10%. Therefore, incorporating a grid structure within the parallel plate detector can significantly improve the time response characteristics of the gas detector, providing an insight for future detector enhancements.

Epitope-Directed Antibody Elicitation by Genetically Encoded Chemical Cross-Linking Reactivity in the Antigen.

No current methods can selectively elicit an antibody response to a specific conformational epitope in a whole antigen in vivo. Here, we incorporated Nε-acryloyl-l-lysine (AcrK) or Nε-crotonyl-l-lysine (Kcr) with cross-linking activities into the specific epitopes of antigens and immunized mice to generate antibodies that can covalently cross-link with the antigens. By taking advantage of antibody clonal selection and evolution in vivo, an orthogonal antibody-antigen cross-linking reaction can be generated. With this mechanism, we developed a new approach for facile elicitation of antibodies binding to specific epitopes of the antigen in vivo. Antibody responses were directed and enriched to the target epitopes on protein antigens or peptide-KLH conjugates after mouse immunization with the AcrK or Kcr-incorporated immunogens. The effect is so prominent that the majority of selected hits bind to the target epitope. Furthermore, the epitope-specific antibodies effectively block IL-1ß from activating its receptor, indicating its potential for the development of protein subunit vaccines.

Mapping trends and hotspot regarding testicular torsion: A bibliometric analysis of global research (2000-2022).

Background: Testicular torsion is an acute scrotal disorder requiring immediate emergency treatment. Ischemic injury and reperfusion injury are important causes of oxidative stress and irreversible oxidative damage after testicular torsion. Although a large number of literatures have discussed the causes and treatment of testicular torsion, there is currently a lack of systematic exploration of the historical evolution of testicular torsion and the construction of a knowledge framework. Method: The Web of Science Core Collection was searched for studies on testicular torsion published between 2000 and 2022. The basic data of the literature were analyzed by using Excel and CiteSpace software. Result: A total of 1,007 publications on testicular torsion published were found in 64 countries between 2000 and 2022, with an increasing annual publication level. Early detection, early diagnosis and early treatment of testicular torsion had always been at the core of clinical practice, and the pathological cascade reaction of ischemic injury and ischemia-reperfusion injury after testicular torsion were also at the core of basic research. Emphasis had been placed on the development of protective drugs for ischemia and reperfusion after testicular torsion in various countries, regions and institutions. Conclusion: Over the past 20 years, the research on testicular torsion had been widely concerned. Hot topics in testicular torsion in recent years were ischemia-reperfusion injury, oxidative stress, rat, doppler ultrasonography, diagnosis and orchiectomy. This article may provide a useful resource for clinicians and basic researchers regarding testicular torsion.

China's Gridded Manufacturing Dataset.

The growth of the manufacturing industry is the engine of rapid economic growth in developing regions. Characterizing the geographical distribution of manufacturing firms is critically important for scientists and policymakers. However, data on the manufacturing industry used in previous studies either have a low spatial resolution (or fuzzy classification) or high-resolution information is lacking. Here, we propose a map point-of-interest classification method based on machine learning technology and build a dataset of the distribution of Chinese manufacturing firms called the Gridded Manufacturing Dataset. This dataset includes the number and type of manufacturing firms at a 0.01° latitude by 0.01° longitude scale. It includes all manufacturing firms (classified into seven categories) in China in 2015 (4.56 million) and 2019 (6.19 million). This dataset can be used to characterize temporal and spatial patterns in the distribution of manufacturing firms as well as reveal the mechanisms underlying the development of the manufacturing industry and changes in regional economic policies.

Regulation of maltocin synthesis in Stenotrophomonas maltophilia by positive and negative regulators.

Maltocin P28, produced by Stenotrophomonas maltophilia P28, is an R-type phage tail-like bacteriocin (PTLB). Its gene cluster consists of 23 putative genes, including nine nonstructural genes and fourteen structural genes. In this work, three nonstructural genes, mpsA, mpsH and mpsR, were found to encode transcriptional regulators to control maltocin P28 synthesis. MpsA activated the transcription of mpsH and lysis genes. MpsH activated the transcription of structural genes. Under normal growth conditions, MpsR repressed the transcription of mpsA and the structural genes, as well as its own. When S. maltophilia P28 was treated with mitomycin C, an immediate and significant decrease in the amount of MpsR was observed, followed by derepressed expression of mpsA, mpsR and structural genes, a marked rise in the expression of all regulatory and structural genes, and finally a clear increase in the maltocin P28 production. Neither the recA gene nor the lexA gene was found to be involved in the induced synthesis of maltocin P28. Our study indicated that a unique mechanism regulates the expression of maltocin genes in S. maltophilia, representing a novel strategy for balancing the expression of PTLB genes in bacteria.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Ningmitai capsule promotes calculi expulsion after RIRS for 10-20-mm upper urinary stones: a multicenter, prospective, randomized controlled trial.

To evaluate the efficacy and safety of the use of Ningmitai capsule as an adjunctive stone expulsion therapy after RIRS. All patients were diagnosed with upper urinary tract calculi measuring 10-20 mm. The patients who successfully underwent RIRS were randomly assigned to the NMT capsule group (Ningmitai capsule, 1.52 g, three times daily) or the control group for 4 weeks based on the random number table method. The primary endpoints were the stone expulsion rate (SER) and stone-free rate (SFR). The average stone expulsion time (SET), average stone-free time (SFT) and complications were recorded. Between July 2, 2019, and December 17, 2020, 220 participants successfully underwent RIRS across 6 centers; 123 of them were randomized according to the exclusion criteria, and 102 (83%) were included in the primary analysis. The SERs on the 3rd, 7th, 14th and 28th days were significantly increased in the NMT capsule group compared with the control group (78.95% vs. 31.11%, 92.98% vs. 55.56%, 94.74% vs. 64.44%, 100% vs. 82.22%, respectively, p < 0.05). The SFRs on the 3rd and 7th days were not different (p > 0.05), while those on the 14th and 28th days were higher in the NMT capsule group (63.16% vs. 24.44% and 92.98% vs. 68.89%, p < 0.05). The average SET and average SFT of the NMT capsule group were remarkably shorter than those of the control group (p < 0.001). During the follow-up period, there were no significant differences in urine RBC counts between the two groups (p > 0.05). The urine WBC counts of the NMT capsule group were significantly lower than those of the control group on the 14th day (p = 0.011), but there was no difference on the 3rd, 7th or 28th day (p > 0.05). The analgesic aggregate of the NMT capsule group was also much lower (p = 0.037). There were no significant differences in adverse events (p > 0.05), and they improved significantly without sequelae. This study indicated that NMT capsules can significantly promote stone clearance and are more effective and safer for upper urinary calculi after RIRS.Trial registration Chinese Clinical Trial Registration No. ChiCTR1900024151.Date of registration June 28, 2019.

Research on the evolution and driving forces of the manufacturing industry during the "13th five-year plan" period in Jiangsu province of China based on natural language processing.

The development of China's manufacturing industry has received global attention. However, research on the distribution pattern, changes, and driving forces of the manufacturing industry has been limited by the accessibility of data. This study proposes a method for classifying based on natural language processing. A case study was conducted employing this method, hotspot detection and driving force analysis, wherein the driving forces industrial development during the "13th Five-Year plan" period in Jiangsu province were determined. The main conclusions of the empirical case study are as follows. 1) Through the acquisition of Amap's point-of-interest (POI, a special point location that commonly used in modern automotive navigation systems.) data, an industry type classification algorithm based on the natural language processing of POI names is proposed, with Jiangsu Province serving as an example. The empirical test shows that the accuracy was 95%, and the kappa coefficient was 0.872. 2) The seven types of manufacturing industries including the pulp and paper (PP) industry, metallurgical chemical (MC) industry, pharmaceutical manufacturing (PM) industry, machinery and electronics (ME) industry, wood furniture (WF) industry, textile clothing (TC) industry, and agricultural and food product processing (AF) industry are drawn through a 1 km× 1km projection grid. The evolution map of the spatial pattern and the density field hotspots are also drawn. 3) After analyzing the driving forces of the changes in the number of manufacturing industries mentioned above, we found that manufacturing base, distance from town, population, GDP per capita, distance from the railway station were the significant driving factors of changes in the manufacturing industries mentioned above. The results of this research can help guide the development of manufacturing industries, maximize the advantages of regional factors and conditions, and provide insight into how the spatial layout of the manufacturing industry could be optimized.

TaWRKY10 plays a key role in the upstream of circadian gene TaLHY in wheat.

TaLHY is an MYB transcription factor (TF) that is upregulated by salicylic acid induction and shows circadian rhythms. However, the study of the upstream regulatory factors is still unclear. In this study, we cloned the promoter sequence of the TaLHY homologous genes, verified the activity of the promoters, and identified important regions that affect promoter activity. Furthermore, we explored a possible upstream regulator of TaLHY, named TaWRKY10, which played a key role in the expression of TaLHY. We found that the three promoters pTaLHYa, pTaLHYb, and pTaLHYd had transcriptional activity in wheat protoplasts. All three promoters have W-Box, which can bind to WRKY TFs. Using virus-induced gene silencing (VIGS), after silencing TaWRKY10, the resistance of ChuanNong 19 (CN19) to stripe rust pathogen strain CYR32 was lost, and the expression level of the TaLHY homologous gene decreased. At the same time, in wheat protoplasts, the transcriptional activity of TaLHY homologous promoters improved after TaWRKY10 overexpression. This indicates that TaWRKY10 is a key gene for wheat immune response to stripe rust, and this gene may bind to TaLHYa, TaLHYb, and TaLHYd promoters to regulate the expression of TaLHY.

Effectors of Puccinia striiformis f. sp. tritici Suppressing the Pathogenic-Associated Molecular Pattern-Triggered Immune Response Were Screened by Transient Expression of Wheat Protoplasts.

Puccinia striiformis f. sp. tritici (Pst) is an important pathogen of wheat (Triticum aestivum L.) stripe rust, and the effector protein secreted by haustoria is a very important component involved in the pathogenic process. Although the candidate effector proteins secreted by Pst haustoria have been predicted to be abundant, few have been functionally validated. Our study confirmed that chitin and flg22 could be used as elicitors of the pathogenic-associated molecular pattern-triggered immune (PTI) reaction in wheat leaves and that TaPr-1-14 could be used as a marker gene to detect the PTI reaction. In addition, the experimental results were consistent in wheat protoplasts. A rapid and efficient method for screening and identifying the effector proteins of Pst was established by using the wheat protoplast transient expression system. Thirty-nine Pst haustorial effector genes were successfully cloned and screened for expression in the protoplast. We identified three haustorial effector proteins, PSEC2, PSEC17, and PSEC45, that may inhibit the response of wheat to PTI. These proteins are localized in the somatic cytoplasm and nucleus of wheat protoplasts and are highly expressed during the infection and parasitism of wheat.

Circular RNA_0001495 increases Robo1 expression by sponging microRNA-527 to promote the proliferation, migration and invasion of bladder cancer cells.

Bladder cancer (BCa) is a heterogeneous disease that poses great threats on public health. Increasing studies have identified the vital functions of circular RNAs (circRNAs) in BCa treatment. Hence, this current study set out to explore the modulatory role of circ_0001495 in BCa development. First, the expression of circ_0001495 was determined by reverse transcription quantitative polymerase chain reaction. Cell biological processes were then analyzed after altering the circ_0001495 expression in T24 cells. Next, interactions among circ_0001495, microRNA-527 (miR-527) and roundabout guidance receptor 1 (Robo1) were investigated by dual luciferase reporter gene assay, RNA pull down assay and FISH assay. Lastly, xenograft tumors in nude mice were established to explore the effect of circ_0001495 in vivo. It was found that circ_0001495 was highly expressed in BCa tissues and cells, and was further correlated with poor prognosis in BCa patients. In addition, circ_0001495 inhibited the activity of miR-527 by acting as a sponge to sponge miR-527, which further elevated the Robo1 expression. Lastly, circ_0001495 was found to promote the proliferation, migration and invasion of BCa cells in vitro through the miR-527/Robo1 axis and promote the growth and metastasis of BCa tumors in vivo. Altogether, findings in our study highlight the promoting role of circ_0001495 in the progression of BCa by increasing Robo1 via sponging miR-527, representing a promising target for BCa management.

LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5.

Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-ß1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.