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The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms. Members of the MAM consortium recently undertook an interlaboratory study to evaluate the industry-wide status of MAM. Here we present the results of this study as they pertain to the targeted attribute analytics component of MAM, including investigation into the sources of variability between laboratories and comparison of MAM data to orthogonal methods. These results are made available with an eye toward aiding the community in further optimizing the method to enable its more frequent use in the QC environment.

We examine the information sharing behavior of stakeholders in the sustainable supply chain of water transfer projects in the context of "Migrating to Cloud, Using Digital Tools and Enabling Intelligence". We explored the evolution of the information sharing behavior of supply chain stakeholders using the China South-North Water Transfer Project as an example, and conducted simulations using MATLAB software to verify the optimal path of the supply chain. The results show that the information sharing behavior of stakeholders in the sustainable supply chain of water transfer projects is influenced by the water consumption of each municipality, the payment strategy of the South-North Water Transfer Project Fund and the cost of updating big data technology. Whether to obtain downstream demand information from the cloud. The upstream and downstream water supply companies should integrate the use of big data and real-time cloud-based intelligent services to make themselves and their partners more profitable in both directions, and to promote the overall coordinated development of a sustainable supply chain for water transfer projects.

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development. First, 4195 protein-coding genes (PCGs, mRNAs) were obtained from the The Cancer Genome Atlas (TCGA) database, in which 1148 lncRNAs were differentially expressed in PCa. Then, 44,270 pairs of co-expression relationships were calculated between 612 lncRNAs and 2742 mRNAs, of which 42,596 (96%) were positively correlated. Among the 612 lncRNAs, 392 had the potential to interact with the promoter region to form DNA:DNA:RNA triplexes, from which lncRNA AD000684.2(AC002128.1) was selected for further validation. AC002128.1 was highly expressed in PCa. Furthermore, AD000684.2 positively regulated the expression of the correlated genes. In addition, AD000684.2 formed RNA–DNA triplexes with the promoter region of the regulated genes. Functional assays also demonstrated that lncRNA AD000684.2 promotes cell proliferation and motility, as well as inhibits apoptosis, in PCa cell lines. The results suggest that AD000684.2 could positively regulate the transcription of target genes via triplex structures and serve as a candidate prognostic biomarker and target for new therapies in human PCa.

Background: Adenomatoid Tumor of the Adrenal Gland (AT-AG) are very rare. As the most commonly used clinical examination program, CT scan can make benign and malignant diagnosis by evaluating the characteristics of lesion shape, density and blood vessels, and provide imaging basis for treatment decisions.Objective: To investigate the clinical, pathological and CT imaging features of AT-AG.Methods: The clinical, pathological and CT findings of three AT-AG patients confirmed by surgery or pathology were reviewed and analyzed with reference to nine cases in literature reports.Results: Among the 12 patients with AT-AG, 11 were male, with a median age of 40 years; 11 were diagnosed by physical examination or accident, while 1 was treated for right lumbago. Pathologically, they were characterized by microcapsule/glandular tube structures, absence of cell heteromorphosis and mitosis, positive immunohistochemical mesothelial markers, and negative endothelial markers; In addition, all of them were confirmed with single adrenal cystic or cystic solid masses on CT, including 2 with multilocular cyst and 3 with calcification. Among them, nine (75%) were oval, with the long diameter parallel to the long axis of adrenal gland, and 8 (67%) showed mild and moderate enhancement of capsule wall and solid components on enhanced scan.Conclusion: AT-AG is more common in young and middle-aged men than other population groups, and it constitutes microcapsule/glandular structures under microscope. Its immune histo chemical mesothelial markers show positive, while endothelial markers are negative. CT findings reveal a mostly oval solitary cyst or solid mass, parallel to the long axis of adrenal gland, with mild and moderate enhancement on enhanced CT scan. Thus, being familiar with the clinical, pathological and CT features of AT-AG helps boost the understanding of the disease

Long noncoding RNAs (lncRNAs) have been found as novel participants in the pathophysiology of prostate cancer (PCa), which is predominantly regulated by androgen and its receptor. The biological function of androgen-responsive lncRNAs remains poorly understood. Here, we identified that lncRNA RP11-1023L17.1, which is highly expressed in PCa. RP11-1023L17.1 expression, can be directly repressed by the androgen receptor in PCa cells. RP11-1023L17.1 depletion inhibited the proliferation, migration, and cell cycle progression, and promoted the apoptosis of PCa cells, indicating that RP11-1023L17.1 acts as an oncogene in PCa cells. Microarray results revealed that RP11-1023L17.1 depletion downregulated the c-Myc transcription signature in PCa cells. RP11-1023L17.1 depletion-induced cellular phenotypes can be overcome by ectopically overexpressed c-Myc. Mechanistically, RP11-1023L17.1 represses FBXO32 mRNA expression, thereby enhancing c-Myc protein stability by blocking FBXO32-mediated c-Myc degradation. Our findings reveal the previously unrecognized roles of RP11-1023L17.1 in c-Myc-dependent PCa tumorigenesis.

Establishing a diversified ecological compensation mechanism for inter-provincial river basins is an important measure to effectively balance the relationship between water quality protection and economic development. However, in the practice of diversified ecological compensation of river basin water ecology, the conflicts of interests and contradictions between upstream and downstream governments in water resources management and protection become an important obstacle to the sustainable development of the river basin. To solve the above problems, this paper proposes the operation mode of a diversified ecological compensation mechanism based on collaborative governance among local governments, to promote the diversified ecological compensation mechanism to effectively match the demands of interest subjects and dynamically adjust the combination of compensation methods. The evolutionary game model of diversified ecological compensation cooperative governance between upstream and downstream governments is constructed, the dynamic simulation analysis is carried out by taking Shaanxi and Henan provinces as examples. The results show that the higher the initial willingness of upstream governments to diversify ecological compensation, the faster the stability of the collaborative governance system. When the fund allocation ratio of the diversified compensation method is biased to the government compensation, the stable state of the system can be achieved faster. The agreement guarantee cost has a greater impact on the upstream government, and it is easier to achieve system stability when the revenue distribution ratio is biased toward the downstream government. A good incentive and constraint mechanism can effectively promote the the system’ stability and have a more significant impact on the downstream government.

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.

Introduction Prostate cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of cancer-related death in males in the United States. Despite the initial efficacy of androgen deprivation therapy in prostate cancer (PCa) patients, most patients progress to castration-resistant prostate cancer. However, the mechanisms underlying the androgen-independent progression of PCa remain largely unknown. Methods In this study, we established a PCa cell line (LNCaP-AI) by maintaining LNCaP cells under androgen-depleted conditions. To explore the cellular and molecular mechanisms of androgen-independent growth of PCa, we analyzed the gene expression patterns in androgen-independent prostate cancer (AIPC) compared with that in androgen-dependent prostate cancer (ADPC). KEGG pathway analysis revealed that Wnt signaling pathways were activated after androgen deprivation therapy (ADT). In vitro experiments showed that the inhibition of Wnt pathway reduced AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. Furthermore, WNT5A, LEF1 were identified as direct targets of AR by chromatin immunoprecipitation (ChIP) assay and public ChIP-seq datasets analysis. Results In the present study, we found a regulatory mechanism through which crosstalk between androgen receptor (AR) and Wnt signals promoted androgen-independent conversion of PCa. The Wnt pathway was inhibited by androgen in androgen-dependent prostate cancer cells, but this blocking effect was not elicited in androgen-independent prostate cancer (AIPC) cells. Moreover, Wnt pathway genes WNT5A and LEF1 were directly downregulated by AR. In vitro experiments showed that inhibition of the Wnt pathways repressed AIPC cell growth by inhibiting cell cycle progression and promoting apoptosis. We found that WNT5A and LEF1 were downregulated in low-grade PCa but upregulated in metastatic PCa. Conclusion In summary, we revealed that crosstalk between AR and Wnt signaling pathways promotes androgen-independent growth of PCa, which may provide novel therapeutic opportunities for castration-resistant prostate cancer.

PurposeThe purpose of this paper is to investigate the impacts of different gray markets’ structures on both supply chain decisions and associated profits.Design/methodology/approachWithin the context of gray markets, using game theory approach in this paper, supply chains have been considered as assets of manufacturers, distributors and speculators, within which manufacturers sell products to distinctive markets either directly or through authorized distributors, while speculators buy products from a lower price market and then sell them in a higher price market. Our study has examined different decision variables within such a framework.FindingsConsidering a situation where one manufacturer sells its products either directly in one market (Market 1) or through its authorized distributor (Market 2), due to different products prices in both markets, results have shown that, when market elasticity is less than its critical value, a speculator can sell a gray market product arbitrage in market 2, whereas when the market elasticity is greater than its critical value, a speculator can sell a gray market product arbitrage in market 1. In addition, manufacturers—as leaders of Stackelberg game—are always the most profitable stakeholders within a gray market supply chain.Practical implicationsIn this study, equilibrium results for each market have been obtained, optimal results have been compared, and accordingly, valuable insights have been developed. Such results would help managers to take better managerial decisions, as well as strategizing policies in gray markets.Originality/valueIn this paper, we have considered a gray market where both distributors and speculators exist and act as parallel channels. To the best of our knowledge, the extant literature focuses either on distributors or speculators, but never concurrently on both. In fact, the coexistence of one distributor and one speculator in a gray market will impact their own decisions, as well as both decisions and profits of other stakeholders, and hence, will exert an impact on the manufacturer side.

This study aimed to evaluate the impact of updated pediatric hypertension (HTN) criteria (the 2017 AAP Guidelines) on prevalence estimates of HTN and prehypertension among Chinese children compared to the 2004 Fourth Report. A total of 2093 children aged 7-15 years from five schools in Tianjin, China were selected using a multistage random cluster sampling method. The prevalence of HTN per the 2017 AAP Guidelines (10.1%) was significantly higher than that per the Fourth Report (6.6%), whereas the prevalence of prehypertension per the 2017 AAP Guidelines (6.3%) was significantly lower than that per the Fourth Report (8.8%). From the 2004 Fourth Report to the 2017 AAP Guidelines, a total of 117 (5.6%) children were reclassified to have higher blood pressure. The two criteria had better consistency in the diagnosis of systolic abnormalities than in the diagnosis of diastolic abnormalities. The updated definitions for pediatric HTN have a substantive impact on the prevalence estimation among Chinese children, especially among boys, overweight children, and older children.

Measuring the collaboration of the sustainable supply chain of water diversion projects is of great significance to the sustainable operation of the project. To achieve this, it needs to develop a scientific and reasonable collaboration measurement method. Given the economic, environmental and social benefits of water diversion projects, and based on the theory of the sustainable supply chain, an order parameter index system for collaboration measurement was constructed in this study. The Dematel and Analytic Network Process methods were used to compute the local and global weights of each order parameter. A total of 161 valid questionnaires were collected from residents along the South-to-North Water Diversion Project Middle Route to measure its collaboration from 2018 to 2020. Results showed that the orderliness of the four flow subsystems of the South-to-North Water Diversion Project Middle Route increases year by year. Compared with the other three flow subsystems, the knowledge flow subsystem has a lower level of orderliness, suggesting that communication and exchanges among people along the route should be strengthened. Such findings can help identify the weak link in the collaborative management of the sustainable supply chain of water diversion projects and improve it in a targeted manner.

Human-automation shared control is proposed to reduce the risk of driver disengagement in Level-3 autonomous vehicles. Although previous studies have approved shared control strategy is effective to keep a driver in the loop and improve the driver's performance, over- and under-trust may affect the cooperation between the driver and the automation system. This study conducted a human-in-the-loop driving simulation experiment to assess the effects of trust on driver's behavior of shared control. An expert shared control strategy with longitudinal and lateral driving assistance was proposed and implemented in the experiment platform. Based on the experiment (N=24), trust in shared control was evaluated, followed by a correlation analysis of trust and behaviors. Moderating effects of trust on the relationship between gaze focalization and minimum of time to collision were then explored. Results showed that self-reported trust in shared control could be evaluated by three subscales respectively: safety, efficiency and ease of control, which all show stronger correlations with gaze focalization than other behaviors. Besides, with more trust in ease of control, there is a gentle decrease in the human-machine conflicts of mean brake inputs. The moderating effects show trust could enhance the decrease of minimum of time to collision as eyes-off-road time increases. These results indicate over-trust in automation will lead to unsafe behaviors, particularly monitoring behavior. This study contributes to revealing the link between trust and behavior in the context of human-automation shared control. It can be applied in improving the design of shared control and reducing risky behaviors of drivers by further trust calibration.

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer, circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up‐regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up‐regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock‐down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR‐29a‐3p sponge to up‐regulate SLC25A15 expression by bioinformatics analysis, dual‐luciferase reporter assays and biotinylated RNA pull‐down assays. SLC25A15 could reverse the tumour suppressing roles of knock‐down circFOXO3 in PCa. Of note, we found that miR‐29a‐3p was down‐regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR‐29a‐3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up‐regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

BACKGROUND Long noncoding RNA (lncRNA) plays a vital role in the development of many diseases. The abnormal expression of lncRNA is closely related to the occurrence and development of different kinds of tumors including prostate cancer (PCa). METHODS Differentially expressed lncRNA LINC00304 was identified using a publicly available gene expression data set (GSE38241) and quantitative polymerase chain reaction validation. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict the molecular function of LINC00304. A lncRNA microarray, bioinformatic analysis, and chromatin immunoprecipitation assay were carried out to verify the upstream androgen receptor (AR) signaling pathway. Subsequently, the function of LINC00304 was observed by a series of in vitro assays. RESULTS We observed higher expression of LINC00304 in PCa cells and samples compared with normal prostate cells and tissues. Functional analysis of LINC00304 showed it was related to regulating cell cycle process, cellular developmental process, and focal adhesion. Further, we identified androgen-inhibited lncRNA, LINC00304 as a direct target of AR. A series of functional studies revealed that overexpression of LINC00304 could significantly promote cell proliferation and cell cycle progression in PCa cells. We also find that LINC00304 can significantly promote CCNA1 expression in PCa cells. CONCLUSIONS Our results indicate that LINC00304 may represent a new diagnostic and therapeutic biomarker for PCa.

Background The purpose of this study was to screen the predictive factors of no-reflow after a percutaneous coronary intervention (PCI) in elderly patients with ST-segment elevation myocardial infarction (STEMI), and to construct a nomogram model, to guide clinical treatment. Methods A total of 551 elderly STEMI patients (age >65) underwent direct PCI were randomly classified into training group (n=386, 70%) and validation group (n=165, 30%). All patients in the two groups were divided into a no-reflow group and a normal blood flow group according to whether there was a no-reflow phenomenon. Univariable and multivariable logistic regression analysis was used to analyze the relevant data, including demographic characteristics, clinical characteristics, coronary angiography results, electrocardiogram (ECG) results, and biochemical indicators. Then, a nomogram model was constructed on the screened risk factors. The performance of the nomogram was evaluated in terms of discrimination and calibration. The nomogram was further confirmed in the internal validation group. Additionally, decision curve analysis (DCA) was applied to assess the clinical usefulness of the nomogram. Results Five remarkable risk factors were determined: preoperative TIMI blood flow, the diameter of the target lesion, collateral circulation, pulse pressure, and the number of leads for ST-segment elevation. The nomogram involving these five risk factors showed full calibration and discrimination in the training group, with an AUC of 0.71 (95% CI: 0.66-0.77). It was confirmed in the validation group, and the entire cohort and the AUC were 0.64 (95% CI: 0.56-0.73) and 0.69 (95% CI: 0.65-0.74), respectively. Whether in the training group or the verification group, the calibration curve for the probability of no-reflow phenomenon all showed considerable consistency between prediction by nomogram and actual observation. The decision curve revealed a specific role in our nomogram in clinical practice. Conclusions We set up a nomogram that showed absolute accuracy for the prediction of the risk of no-reflow after primary PCI in elderly STEMI patients.

Background Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort. Methods Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs. Interactions between transcription factors and long noncoding RNAs were validated by RNA immunoprecipitation quantitative PCR. RNA interference assays were performed to explore roles of the selected transcription regulators. Findings Sixteen transcription factors, namely, ETS1, ARID4B, KLF12, GMEB1, HBP1, MXI1, MYC, MAX, PGR, BCL11A, AR, KLF4, SRF, HIF1A, EHF, and ATOH1, were jointly identified as a prognostic signature. Candidate long noncoding RNAs interplaying with the prognostic signature constituent transcription factors were further discovered. Their interactions were randomly checked, and many of them were experimentally proved. Transcription regulation by MYC and its long noncoding RNA partner AL590617.2 was further validated on their candidate targets. Moreover, the regulatory network governed by the transcription factors and their interacting long noncoding RNA partners is illustrated and stored in our LNCTRN database ( https://navy.shinyapps.io/lnctrn ). Interpretation The prognostic signature constituent transcription factors and their interacting long noncoding RNAs may represent promising biomarkers and/or therapeutic targets for prostate cancer. Furthermore, the computational framework proposed in the present study can be utilized to explore critical transcriptional regulators in other types of cancer. Funding This work was supported by National Natural Science Foundation of China and Fudan University.

To characterize the prevalence of hypertension and prehypertension and its association with four anthropometrics among children aged 7–15 years in Tianjin, China, a school-based cross-sectional survey was conducted from May to August 2010. Multistage random cluster sampling was used to select the participants. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were measured. Hypertension and prehypertension were identified according to the definition of United State Fourth Report. Logistic regression, linear regression and the area under receiver operating curves (AUC) was used for assessing the association. Among 1898 eligible children, the prevalence of hypertension and prehypertension was 6% and 6.6%, respectively. No statistically significant differences were found between boys and girls. Both linear and logistic regression showed that the four anthropometrics were all positively related to blood pressure value or the risk of prehypertension and hypertension. Of the four anthropometrics, BMI might be the most sensitive indicator for predicting elevated blood pressure, followed by WC and WHtR, whereas WHR had the lowest predicting capacity, with the AUCs being 0.72 (0.68,0.75), 0.69 (0.65,0.73), 0.67 (0.63,0.71), and 0.61 (0.57,0.65), respectively. A significantly increased prevalence of hypertension was observed when BMI > P90 percentiles, but for prehypertension, the risk of prehypertension began to increase when BMI was still at a median level. In conclusion, four anthropometrics all had positive relationship with elevated blood pressure. BMI and WC were superior to WHtR and WHR in predicting elevated blood pressure among children and adolescents.

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA AC016745.3 in the development of PCa. It shows that dihydrotestosterone (DHT) results in the AR-dependent suppression of AC016745.3 expression in the LNCaP androgen-sensitive human prostate adenocarcinoma cell line. In addition, overexpression of AC016745.3 inhibits the proliferation and migration of PCa cells, and suppresses the expression of AR target genes. This research also demonstrates that the protein NONO interacts with AR and functions as an AR co-activator, promoting AR transcriptional activity. Furthermore, using RNA immunoprecipitation (RIP)-PCR experiments, the study demonstrates that both NONO and AR can bind AC016745.3. Moreover, cell phenotypic experiments reveal that NONO can promote cellular proliferation and migration, and that AC016745.3 can partially antagonize the pro-oncogenic functions of NONO in PCa cells. In summary, the results indicate that AC016745.3 can bind NONO, suppressing its ability to promote AR-dependent transcriptional activity. Furthermore, DHT-dependent suppression of AC016745.3 expression can enhance NONO’s promotion effect on AR.

Background. Appreciable findings have pointed out pivotal roles of N6-methyladenosine (m6A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. Methods. A PubMed search was conducted to acquire components of the mRNA m6A machinery. Multiomics integration was performed to systematically investigate the mRNA m6A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m6A readers EIF3D and HNRNPA2B1 were conducted to explore m6A dependence of their functions in prostate cancer cell proliferation and migration. Results. A total of 41 mRNA m6A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m6A machinery were also found. Impact of copy number variation on m6A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m6A regulators related to clinical features and/or survival which were largely m6A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m6A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions. Our report systematically described molecular features of the mRNA m6A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m6A system in prostate cancer.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

No-reflow is an important complication among patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A retrospective study of 1658 STEMI patients undergoing direct PCI was performed. Patients were randomly assigned at a 7:3 ratio into development cohort and validation cohort and into no-reflow and normal blood flow groups. Clinical data and laboratory examinations were compared to identify independent risk factors and establish a no-reflow risk scoring system. In the development cohort (n = 1122), 331 (29.5%) had no-reflow. Multivariate analysis showed age ≥ 65 years (OR = 1.766, 95% confidence interval (CI): 1.313–2.376, P 8 mmol/L (OR = 1.386, 95%CI: 1.007–1.908, P = .045) were related to no-reflow. Receiver operating characteristic (ROC) area under the curve was 0.648 (95%CI: 0.609–0.86). At 0.349 cutoff sensitivity was 42.0%, specificity was 79.3%, positive predictive value (PPV) was 44.7%, negative predictive value (NPV) was 77.4%, P

Recombinant influenza Virus-Like Particle (VLP) vaccines are promising vaccine candidates to prevent influenza, contain two major viral antigenic glycoproteins, Hemagglutinin (HA) and Neuraminidase (NA), on the surface of recombinant VLPs. Accurate quantitation of the mass of these antigenic proteins is important to ensure the product quality and proper dosing. Currently, Single Radial Immunodiffusion (SRID) is a recognized assay for determination of the HA immuno-reactive concentration (potency) in vaccine products, based on immuno-reactivity of HA with strain-specific antisera. The SRID assay, however, requires availability of strain-specific and properly calibrated reagents, which can be time-consuming to generate and calibrate. In addition, the assay is not suitable for quantitation of low abundant proteins, such as NA. In order to accelerate the overall production cycle, we have developed and optimized a high-resolution (HR) LC-MS method for absolute quantitation of both HA and NA protein concentrations in influenza VLP vaccine candidates. In this work, we present the method development, optimization and verification of its suitability for the intended purpose, as a prerequisite for its potential application in Quality Control, by assessing specificity, precision and accuracy, detection characteristics, and dynamic linear range. The method can be also used for other HA/NA containing preparations including in-process samples, purified proteins, whole virus preparations, nano-particle and egg-based vaccine preparations, or for calibration of SRID reference antigens.