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.

Habitual consumption of alcohol with meals and lung cancer: a Mendelian randomization study.

BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.

Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte.

Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine-derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA-16-5p (miR-16-5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR-16-5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual-luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR-16-5p and promote VEGFA in human podocytes (HPDCs). miR-16-5p in hUSCs was transferred through the exosome pathway to HG-treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR-16-5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG-induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR-16-5p were injected into diabetic rats via tail vein, followed by qualification of miR-16-5p and observation on the changes of podocytes, which revealed that overexpressed miR-16-5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR-16-5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

Long Non-coding RNA IRAIN Inhibits VEGFA Expression via Enhancing Its DNA Methylation Leading to Tumor Suppression in Renal Carcinoma.

Aims: Long non-coding RNA IRAIN (lncRNA IRAIN) plays a critical role in numerous malignancies. However, the function of lncRNA IRAIN in renal carcinoma (RC) remains enigmatic. The purpose of this study is to characterize the effects of lncRNA IRAIN on RC progression. Methods: The expression pattern of lncRNA IRAIN and the vascular endothelial growth factor A (VEGFA) in RC tissues and cells was characterized by RT-qPCR and Western blot analysis. The roles of lncRNA IRAIN and VEGFA in the progression of RC were studied by gain- or loss-of-function experiments. Bioinformatics data analysis was used to predict CpG islands in the VEGFA promoter region. MSP was applied to detect the level of DNA methylation in RC cells. The interaction between lncRNA IRAIN and VEGFA was identified by RNA immunoprecipitation and RNA-protein pull down assays. Recruitment of DNA methyltransferases (Dnmt) to the VEGFA promoter region was achieved by chromatin immunoprecipitation. The subcellular localization of lncRNA IRAIN was detected by fractionation of nuclear and cytoplasmic RNA. Cell viability was investigated by CCK-8 assay, cell migration was tested by transwell migration assay, and apoptosis was analyzed by flow cytometry. The expression of epithelial-mesenchymal transition-related and apoptotic factors was evaluated by Western blot analysis. Finally, the effect of the lncRNA IRAIN/VEGFA axis was confirmed in an in vivo tumor xenograft model. Results: LncRNA IRAIN was poorly expressed in RC tissues and cells with a primary localization in the nucleus, while VEGFA was highly expressed. Overexpression of lncRNA IRAIN or knockdown of VEGFA inhibited cell proliferation and migration and induced the apoptosis of RC cells. Bioinformatics analysis indicated the presence of CpG islands in the VEGFA promoter region. Lack of methylation at specific sites in the VEGFA promoter region was detected through MSP assay. We found that lncRNA IRAIN was able to inhibit VEGFA expression through recruitment of Dnmt1, Dnmt3a, and Dnmt3b to the VEGFA promoter region. LncRNA IRAIN was also able to suppress RC tumor growth via repression of VEGFA in an in vivo mouse xenograft model. Conclusion: Our data shows that by downregulating VEGFA expression in RC, the lncRNA IRAIN has tumor-suppressive potential.

LncRNA EMX2OS, Regulated by TCF12, Interacts with FUS to Regulate the Proliferation, Migration and Invasion of Prostate Cancer Cells Through the cGMP-PKG Signaling Pathway.

BACKGROUND: LncRNA EMX2OS (EMX2 opposite strand/antisense RNA) is notably downregulated in prostate cancer (PCa) tissues and may be regarded as a potential molecular biomarker for diagnosis and prognosis. However, its exact role in regulating the development of PCa is obscure. METHODS: The EMX2OS expression was assessed in PCa tissues, paracancer tissues, PCa cells and normal prostate epithelial cells by qPCR. Gain- and loss-of-function experiments were performed to investigate the role of EMX2OS and FUS in cGMP-PKG (cyclic guanosine monophosphate-dependent protein kinase)-mediated proliferation, invasion, and migration in human PCa cell lines DU145 and PC3. Then, the interaction of transcription factor 12 (TCF12) with EMX2OS promoter was confirmed by using the dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RNA binding protein immunoprecipitation and RNA pull-down assays were used to verify the interaction between EMX2OS and FUS protein. Finally, the role of EMX2OS and FUS in tumor growth in vivo was validated in a xenograft nude mouse model. RESULTS: TCF12 and EMX2OS were both downregulated in PCa tissues and cells, and they negatively regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. TCF12 was a transcription factor of EMX2OS. TCF12 and EMX2OS overexpression both down-regulated cell proliferation, migration and invasion, and activated cGMP-PKG pathway in DU145 and PC3 cells. Furthermore, EMX2OS directly bound with FUS protein and had a synergy effect with FUS protein on cGMP-PKG-mediated cell functions, which could be suppressed by (D)-DT-2 (a cGMP-PKG inhibitor). In addition, the overexpression of FUS or EMX2OS individually markedly decreased the volume and weight of tumors in vivo, and co-overexpression of them further inhibited tumor growth. CONCLUSION: EMX2OS, transcriptionally regulated by TCF12, played a synergy role with FUS protein in regulating the proliferation, migration and invasion of PCa cells by activating the cGMP-PKG pathway.

Knockdown of lncRNA PVT1 inhibits prostate cancer progression in vitro and in vivo by the suppression of KIF23 through stimulating miR-15a-5p.

BACKGROUND: Prostate cancer (PCa) greatly threatens men's lives, with high incidence and mortality. Recently, the research of long non-coding RNAs (lncRNAs) has made breakthroughs in the development of human cancers. This study aimed to figure out the role and action mechanism of lncRNA PVT1 (PVT1) in PCa. METHODS: The expression of PVT1, microRNA-15a-5p (miR-15a-5p) and kinesin family member 23 (KIF23) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assays, respectively. The protein levels of KIF23 and proliferation, apoptosis, and epithelial-mesenchymal transition (EMT)-related markers were quantified by western blot. The relationship between miR-15a-5p and PVT1 or KIF23 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Xenograft assay was conducted to determine the role of PVT1 in vivo. RESULTS: The expression of PVT1 and KIF23 was enhanced, while miR-15a-5p expression was reduced in PCa tissues and cells. PVT1 interference inhibited proliferation, migration and invasion but promoted apoptosis of PCa cells. MiR-15a-5p was a target of PVT1, and KIF23 was a target of miR-15a-5p. The inhibition of miR-15a-5p reversed the effects of PVT1 interference and suppressed the roles of KIF23 knockdown. KIF23 expression was regulated by PVT1 through miR-15a-5p. PVT1 interference blocked PCa progression in vivo. CONCLUSION: PVT1 knockdown had effects on the progression of PCa by inhibiting the expression of KIF23 via enriching miR-15a-5p in vitro and in vivo, suggesting that PVT1 might be a novel biomarker for the treatment of PCa.

Epitope-directed antibody selection by site-specific photocrosslinking.

Currently, there are no methods available offering solutions to select and identify antibodies binding to a specific conformational epitope of an antigen. Here, we developed a method to allow epitope-directed antibody selection from a phage display library by photocrosslinking bound antibodies to a site that specifically incorporates a noncanonical amino acid, p-benzoyl-l-phenylalanine (pBpa), on the target antigen epitope. By one or two rounds of panning against antibody phage display libraries, those hits that covalently bind to the proximity site of pBpa on specific epitopes of target antigens after ultraviolet irradiation are enriched and selected. This method was applied to specific epitopes on human interleukin-1ß and complement 5a. In both cases, more than one-third of hits identified bind to the target epitopes, demonstrating the feasibility and versatility of this method.

The role of the CDCA gene family in ovarian cancer.

BACKGROUND: Ovarian cancer is a frequently-occurring reproductive system malignancy in females, which leads to an annual of over 100 thousand deaths worldwide. METHODS: The electronic databases, including GEPIA, ONCOMINE, Metascape, and Kaplan-Meier Plotter, were used to examine both survival and transcriptional data regarding the cell division cycle associated (CDCA) gene family among ovarian cancer patients. RESULTS: All CDCA genes expression levels were up-regulated in ovarian cancer tissues relative to those in non-carcinoma ovarian counterparts. Besides, CDCA5/7 expression levels were related to the late tumor stage. In addition, the Kaplan-Meier Plotter database was employed to carry out survival analysis, which suggested that ovarian cancer patients with increased CDCA2/3/5/7 expression levels had poor overall survival (OS) (P<0.05). Moreover, ovarian cancer patients that had up-regulated mRNA expression levels of CDCA2/5/8 had markedly reduced progression-free survival (PFS) (P<0.05); and up-regulated CDCA4 expression showed remarkable association with reduced post-progression survival (PPS) (P<0.05). Additionally, the following processes were affected by CDCA genes alterations, including R-HAS-2500257: resolution of sister chromatid cohesion; GO:0051301: cell division; CORUM: 1118: Chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression, all of which were subjected to marked regulation since the alterations affected CDCA genes. CONCLUSIONS: Up-regulated CDCA gene expression in ovarian cancer tissues probably played a crucial part in the occurrence of ovarian cancer. The up-regulated CDCA2/3/5/7 expression levels were used as the potential prognostic markers to improve the poor ovarian cancer survival and prognostic accuracy. Moreover, CDCA genes probably exerted their functions in tumorigenesis through the PLK1 pathway.