Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target.

YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, its biological functions in bladder cancer remains to be proven. We analysed variations in YARS1 expression and survival in bladder cancer using multiple data sets, including TCGA-BLCA, GSE13507 and bladder cancer-specific tissue microarrays. Furthermore, we explored the biological functions of YARS1 using transcriptome data. Our findings revealed a noteworthy correlation between YARS1 and immune infiltration in bladder cancer, as determined using the XCELL algorithm and single-cell analysis. In addition, we employed the TIDE algorithm to evaluate the responsiveness of different cohorts to immune checkpoint therapy. We investigated the regulatory associations between YARS1 and various aspects of bladder cancer, including senescence, ferroptosis and stemness. Finally, we established a ceRNA network that is directly linked to the overall prognosis, YARS1 can serve as a prognostic biomarker for bladder cancer; its interaction with MYC has implications for bladder cancer cell senescence, ferroptosis and stemness. Moreover, the identified ceRNA network has potential as a therapeutic target in bladder cancer.

Common immunological and prognostic features of lung and bladder cancer via smoking-related genes: PRR11 gene as potential immunotherapeutic target.

Smoking is a well-known risk factor for non-small-cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA). Despite this, there has been no investigation into a prognostic marker based on smoking-related genes that could universally predict prognosis in these cancers and correlate with immune checkpoint therapy. This study aimed to identify smoking-related differential genes in NSCLC and BLCA, analyse their roles in patient prognosis and immune checkpoint therapy through subgroup analyses, and shed light on PRR11 as a crucial prognostic gene in both cancers. By examining PRR11 co-expressed genes, a prognostic model was constructed and its impact on immunotherapy for NSCLC and BLCA was evaluated. Molecular docking and tissue microarray analyses were conducted to explore the correlation between PRR11 and its reciprocal gene SPDL1. Additionally, miRNAs associated with PRR11 were analysed. The study confirmed a strong link between smoking-related genes, prognosis, and immune checkpoint therapy in NSCLC and BLCA. PRR11 was identified as a key smoking-associated gene that influences the efficacy of immune checkpoint therapy by modulating the stemness of these cancers. A prognostic model based on PRR11 co-expressed genes in BLCA was established and its prognostic value was validated in NSCLC. Furthermore, it was found that PRR11 regulates PDL1 via SPDL1, impacting immunotherapeutic efficacy in both cancers. The involvement of hsa-miR-200b-3p in the regulation of SPDL1 expression by PRR11 was also highlighted. Overall, the study elucidates that PRR11 modulates patient immunotherapy by influencing PDL1 expression through its interaction with SPDL1, with potential upstream regulation by hsa-miR-200b-3p.

Loss of SETD2-mediated downregulation of intracellular and exosomal miRNA-10b determines MAPK pathway activation and multidrug resistance in renal cancer.

SET domain-containing 2 (SETD2) is the most frequently mutated gene among all the histone methyltransferases in clear cell renal cell carcinoma (ccRCC). Microarrays, RNA sequencing analysis and exosomes analysis of cellular supernatant were performed after transfection A498 cells with si-SETD2 or siRNA of negative control. Chromatin immunoprecipitation and Luciferase reporter assay were conducted to evaluate the interaction between SETD2 and miR-10b. Functional and drug experiments in vitro and in vivo were performed to verify the role of SETD2, miR-10b and MAP4K4. The results showed that loss of SETD2 mediated downregulation of intracellular and exosomal microRNA-10b. MAP4K4 were relevant to oncogenesis of ccRCC caused by loss of SETD2 and miR-10b. SETD2 could directly target miR-10b and regulate the expression of multidrug resistance (MDR)-1 (P-gp170) through JNK pathway, which was one of the downstream pathways of MAP4K4. The coordinated expression of SETD2/H3K36me3/miR-10b/MAPKs/JNK/MDR pathway was revealed to the progression of ccRCC.

Robust H-Infinity Tracking Control for a Valve-Controlled Hydraulic Motor System with Uncertain Parameters in the Complex Load Environment.

A valve-controlled hydraulic motor system operating in a complex environment is subject to complex load changes. In extreme cases, the load can be regarded as a disturbance signal with complex frequency and strong amplitude fluctuations, which greatly affects the speed stability of the hydraulic motor and reduces the operating efficiency. In this paper, the structure of valve-controlled hydraulic motor systems is analyzed, and a valve-controlled hydraulic motor system model with uncertain parameters is established after considering the actual target parameter error and model linearization error. Different from the common H-infinity control, which regards the load disturbance as external disturbance, this paper presents a robust H-infinity tracking control strategy, which considers uncertain parameters and the load torque of the valve-controlled hydraulic motor system as internal disturbances. The simulation results show that the proposed control scheme has better control characteristics and robustness than the traditional PID control.

Three-dimensional printing - Assisted planning for complete and safe resection of retroperitoneal tumor.

BACKGROUND: Surgery is usually recommended to treat retroperitoneal tumors. However, complete surgical resections often remain challenging. OBJECTIVE: To assess the assistant role of three-dimensional (3D) imaging and printing model in retroperitoneal tumor resection, as well as compare the difference between 3D printing and computed tomography (CT) in preoperative planning and confidence building. METHODS: We admitted a patient with retroperitoneal mass (13.0×6.4×14.8 cm) adjacent to important abdominal blood vessels whose surgery was thought to be difficult. 3D printing and CT was arranged. A novel questionnaire and scoring system consisting of surgery difficulty and safety were designed to compare doctors understanding and confidence for surgery based on 3D printing and CT. Twenty-four doctors completed the scoring table based on CT and then 3D imaging, respectively. Paired t-test was applied for statistics analysis. RESULTS: Preoperative evaluation based on 3D printing indicated that the tumor could be removed completely. The operation lasted 120 minutes to successfully remove the tumor and the estimated blood loss was less than 100 ml. Scores based on 3D printing is significantly higher than CT in difficulty and safety of surgery (p < 0.001). Interestingly, the junior doctors seem to benefit more from 3D printing than the senior doctors. CONCLUSIONS: 3D imaging and printing model provides greater help for preoperative planning and confidence building than using CT in resection of retroperitoneal tumor, especially for the junior doctors.

lncRNA GAS5 promotes M1 macrophage polarization via miR-455-5p/SOCS3 pathway in childhood pneumonia.

OBJECTIVES: We herein aimed to explore whether growth arrest-specific 5 (GAS5) promotes M1 macrophage polarization in childhood pneumonia and to investigate the underlying mechanism. METHODS: Relative GAS5 and miR-455-5p expression and suppressor of cytokine signaling 3 (SOCS3) messenger RNA level were examined using quantitative reverse transcription polymerase chain reaction. Protein expression of SOCS3 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway-related proteins was detected using western blot analysis. Luciferase activity assay was performed to test whether miR-455-5p could bind to GAS5 or SOCS3. The macrophage phenotype was determined using flow cytometry analysis and enzyme-linked immunosorbent assay. RESULTS: The macrophage polarization toward the M2 phenotype was observed in peripheral blood from pneumonia children. Furthermore, GAS5 and SOCS3 expression were upregulated but miR-455-5p downregulated in human monocyte-derived macrophages from pneumonia children compared with the control group. Furthermore, GAS5 acted as a sponge for miR-455-5p to facilitate SOCS3 expression. Moreover, miR-455-5p mimic and SOCS3 knockdown significantly reversed the GAS5 overexpression-mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization. CONCLUSION: GAS5 promotes M1 macrophage polarization by acting as a competing endogenous RNA of miR-455-5p to facilitate SOCS3 expression in childhood pneumonia.

Mini-Percutaneous Nephrolithotomy with Ureter Catheter: A Safe and Effective form of mPCNL Offers Better Quality of Life.

OBJECTIVE: To compare outcomes and postoperative quality of life (QoL) among patients with kidney stone who received mini-percutaneous nephrolithotomy (mPCNL), partial tubeless mPCNL or mPCNL with ureter catheter in a prospective randomized clinical trial. METHODS: From May 2017 to December 2017, 60 patients with kidney stone who underwent mPCNL were randomized into 3 groups: Group I (mPCNL), Group II (partial tubeless mPCNL), Group III (mPCNL with ureter catheter). We evaluated perioperative characteristics, stone clearance, analgesic requirements and QoL by using the Wisconsin Stone QOL questionnaire. RESULTS: The age, gender, stone diameter, body mass index, length of operation, drop in hemoglobin and stone-free rates for the 3 groups were similar among these groups. However, the postoperative visual analog scale and the analgesic requirement in Group II were significantly the lowest (p < 0.05). According to Wisconsin Stone QOL questionnaire, compared to Group I, statistical significant difference in the QoL was seen in Group II and III, indicating a meaningful and immediate improvement in the postoperative QoL following mPCNL. CONCLUSION: Compared with standard and partial tubeless mPCNL, mPCNL with ureter catheter is a safe and useful form of mPCNL, which can offer better QoL and is more cost effective.

Complete resection of adult prostatic rhabdomyosarcoma with 3D video and printing model: A case report and literature review.

Prostatic rhabdomyosarcoma (RMS) is a subtype of prostate sarcoma which is rarely reported in adults and usually huge in size. Although there is no consensus on the standard therapy to prostatic RMS, complete resection with negative margin is identified as the best way for maximum survival time. However, to remove a much enlarged prostate completely from a RMS patient is still a very difficult task for a skilled urologist so far. As three-dimension (3D) technology becomes more widely used in medicine, surgeons have the opportunity to challenge previously impossible surgery. In this paper, we reported a 36-year-old male patient with a 9.6*5.3*7.6 cm prostatic RMS. With the aid of 3D reconstructed video and printing model, the giant tumor was entirely removed without surgery complications and adjacent organs injury. The patient was alive and had no recurrence after 18 months from surgery. This case revealed that 3D reconstruction technology could help in the preoperative assessment and gave benefits to both patients and surgeons.

Pure Small Cell Carcinoma of Prostate: A Report of 8 Cases.

PURPOSE: To describe characteristics of pure small cell carcinoma of prostate (SCCP) and assess the prognostic factors. PATIENTS AND METHODS: We summarized data of pure SCCP from published studies and ours and made Kaplan-Meier analysis and Cox regression to evaluate prognosis factors. RESULTS: A total of 2,213 patients with prostate cancer was identified, of which eight (0.36%) patients were pure SCCP. The mean age at diagnosis was 61 years old. And there were 2 patients diagnosed at 34 and 50 years old respectively. Symptoms of these patients were similar to patients with prostate adenocarcinoma. Serum prostate specific antigen of 7 patients was at normal level. Five patients received chemotherapy, average overall survival (OS) was 9.75 months; 3 only received conservative treatment, average OS was 4 months. By univariate and multivariate Cox analysis, chemotherapy is an independent predictor of survival. Kaplan-Meier analysis demonstrated that chemotherapy was associated with longer OS. CONCLUSION: Clinical characteristics, examination and treatment strategy of pure SCCP are very different from prostate adenocarcinoma. According to the data from published studies and from our studies, the average survival of patients receiving chemotherapy is longer than those who received other treatment modalities.

Hydrostatic bearing groove multi-objective optimization of the gear ring housing interface in a straight-line conjugate internal meshing gear pump.

The lubrication performance of a straight-line conjugate internal meshing gear pump is poor under the low-speed, high-pressure operating conditions of the volumetric servo speed control system, and it is difficult to establish a full fluid lubricating oil film between the gear ring and the housing. This leads to significant wear and severe heating between the gear ring and the housing. The lubrication performance of the interface moving pair of the electro-hydraulic actuator pump gear ring housing can be improved by designing a reasonable lubrication bearing structure for the gear ring housing. In this study, a multi-field coupling multi-objective optimization model was established to improve lubrication performance and volumetric efficiency. The whole model consists of the dynamic model of the gear ring components, the fluid lubrication model of the gear ring housing interface, the oil film formation and sealing model considering the influence of temperature, and the multi-objective optimization model. The comprehensive performance of the straight-line conjugate internal meshing gear pump was verified experimentally using a test bench. The results show that the lubrication performance is improved, the mechanical loss is reduced by 31.52%, and the volumetric efficiency is increased by 4.91%.

Identification of metastasis-related genes for predicting prostate cancer diagnosis, metastasis and immunotherapy drug candidates using machine learning approaches.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients. Identifying novel and effective biomarkers is essential for understanding the mechanisms of metastasis in PCa patients and developing successful interventions. METHODS: Using the GSE8511 and GSE27616 data sets, 21 metastasis-related genes were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequent functional analysis of these genes was conducted on the gene set cancer analysis (GSCA) website. Cluster analysis was utilized to explore the relationship between these genes, immune infiltration in PCa, and the efficacy of targeted drug IC50 scores. Machine learning algorithms were then employed to construct diagnostic and prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression analysis highlighted the significant role of POLD1 and examined its association with DNA methylation. Finally, molecular docking and immunohistochemistry experiments were carried out to assess the binding affinity of POLD1 to PCa drugs and its impact on PCa prognosis. RESULTS: The study identified 21 metastasis-related genes using the WGCNA method, which were found to be associated with DNA damage, hormone AR activation, and inhibition of the RTK pathway. Cluster analysis confirmed a significant correlation between these genes and PCa metastasis, particularly in the context of immunotherapy and targeted therapy drugs. A diagnostic model combining multiple machine learning algorithms showed strong predictive capabilities for PCa diagnosis, while a transfer model using the LASSO algorithm also yielded promising results. POLD1 emerged as a key prognostic gene among the metastatic genes, showing associations with DNA methylation. Molecular docking experiments supported its high affinity with PCa-targeted drugs. Immunohistochemistry experiments further validated that increased POLD1 expression is linked to poor prognosis in PCa patients. CONCLUSIONS: The developed diagnostic and metastasis models provide substantial value for patients with prostate cancer. The discovery of POLD1 as a novel biomarker related to prostate cancer metastasis offers a promising avenue for enhancing treatment of prostate cancer metastasis.

Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches.

Background: Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated. Method: This study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3. Result: Overall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis. Conclusion: Our study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.

Multi-omics analysis and experimental validation of the value of monocyte-associated features in prostate cancer prognosis and immunotherapy.

Background: Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD. Method: Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. Result: Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis. Conclusion: Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.

JAM3: A prognostic biomarker for bladder cancer via epithelial­mesenchymal transition regulation

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial­mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-Cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.

A systematic review of the modelling of patient arrivals in emergency departments.

Background: Accident and Emergency Department (AED) is the frontline of providing emergency care in a hospital and research focusing on improving decision-makings and service level around AED has been driving a rising number of attentions in recent years. A retrospective review among the published papers shows that related research can be classified according to six planning modules: demand forecasting, days-off scheduling, shift scheduling, line-of-work construction, task assignment and staff assignment. As patient arrivals demand forecasts enable smooth AED operational planning and help decision-making, this article conducted a systematic review on the statistical modelling approaches aimed at predicting the volume of AED patients' arrival. Methods: We carried out a systematic review of AED patient arrivals prediction studies from 2004 to 2021. The Medline, ScienceDirect, and Scopus databases were searched. A two-step screening process was carried out based on the title and abstract or full text, and 35 of 1,677 articles were selected. Our methods and results follow the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We categorise AED methods for modelling patient arrivals into four main classes: regression, time series, artificial intelligence and time series regression. Choice of prediction model, selection of factors and model performance are compared. Finally, we discuss the advantages and limitations of the models and suggest future research directions. Results: A total of 1,677 papers that fulfilled the initial searching criteria was obtained from the three databases. Based on the first exclusion criteria, 1,603 articles were eliminated. The remaining 74 full text articles were evaluated based on the second exclusion criteria. Finally, 35 articles were selected for full review. We find that the use of artificial intelligence-based model has risen in recent years, from the view of predictive model selection. The calendar-based factors are most commonly used compared with other types of dependent variables, from the view of dependent variable selection. Conclusions: All AEDs are inherently different and different covariables may have different effects on patient arrivals. Certain factors may play a key role in one AED but not others. Based on results of meta-analysis, when modelling patient arrivals, it is essential to understand the actual AED situation and carefully select relevant dominating factors and the most suitable modelling method. Local calibration is also important to ensure good estimates.

TMT-based proteomics analysis of growth advantage of triploid Apostichopus japonicus.

Polyploid breeding can produce new species with a faster growth rate, higher disease resistance, and higher survival rate, and has achieved significant economic benefits. This study investigated the protein differences in the body wall of triploid Apostichopus japonicus and diploid A. japonicus using isotope-labeled relative and absolute quantitative Tandem Mass Tag technology. A total of 21,096 independent peptides and 4621 proteins were identified. Among them, there were 723 proteins with significant expression differences, including 413 up-regulated proteins and 310 down-regulated proteins. The differentially expressed proteins (DEPs) were enriched in 4519 Gene Ontology enrichment pathways and 320 Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Twenty-two key DEPs related to important functions such as growth and immunity of triploid A. japonicus were screened from the results, among which 20 were up-regulated, such as cathepsin L2 cysteine protease and fibrinogen-like protein A. Arylsulfatase A and zonadhesin were down-regulated. The up-regulated proteins were mainly involved in oxidative stress response, innate immune response, and collagen synthesis in triploid A. japonicus, and the down-regulated proteins were mainly associated with the sterility of triploid A. japonicus. In addition, the transcriptome and proteome were analyzed jointly to support proteome data. In this study, the differences in protein composition between triploid and diploid A. japonicus were analyzed for the first time, and the results revealed the underlying reasons for the growth advantage of triploid A. japonicus.

Comprehensive analysis of integrin αvß3/α6ß1 in prognosis and immune escape of prostate cancer.

Integrin αvß3/α6ß1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvß3/α6ß1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvß3/α6ß1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvß3/α6ß1 in predicting prognosis, TP53 mutation and immune escape in PCa.

A new immune-related gene signature predicts the prognosis and immune escape of bladder cancer.

BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.

Iterative Learning Control for Output Tracking of Nonlinear Systems With Unavailable State Information.

This work presents a novel design framework of adaptive iterative learning control (ILC) approach for a class of uncertain nonlinear systems. By using the closed-loop reference model that can be viewed as an observer, the proposed adaptive ILC approach can be adapted to deal with the output tracking problem of nonlinear systems with unavailable system states. In the systems considered, two classes of uncertainties are taken into account, including parametric input disturbances and input distribution uncertainties. To facilitate the controller design and convergence analysis, the composite energy function (CEF) methodology is employed. The design framework in this brief is novel and widely applicable, which extends the CEF-based ILC approach to output tracking control of nonlinear systems without requiring full knowledge of state information and complicated observer design process. To show the effectiveness of the proposed design framework and control algorithms, two numerical examples are illustrated.

Erratum: Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.37628.].