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Abstract Purpose Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, a key cancer factor, suggests a potential target for treating metastatic cancer. However, a complete understanding of the link between propionate metabolism-related genes (PMRGs) and bladder cancer is lacking. Methods From the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival and pathway analyses were conducted between these clusters. The PMRGs model, created through univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, was assessed for prognostic significance using Kaplan–Meier and receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, and immunotherapy analyses. Finally, the expression of HSD17B1 essential genes was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation through Transwell, wound healing, colony-formation, and EDU assays. Results We discovered two distinct subcategories (CA and CB) within BLCA using NMF analysis, with CA demonstrating significantly better overall survival compared to CB. Additionally, six PMRGs emerged as critical factors associated with propionate metabolism and prognosis. Kaplan–Meier analysis revealed that high-risk PMRGs were correlated with a poorer prognosis in BLCA patients. Moreover, significant differences were observed between the two groups in terms of infiltrated immune cells, immune checkpoint expression, TME scores, and drug sensitivity. Notably, we found that suppressing HSD17B1 gene expression inhibited the invasion of bladder cancer cells. Conclusion Our study proposes molecular subtypes and a PMRG-based score as promising prognostic indicators in BLCA. Additionally, cellular experiments underscore the pivotal role of HSD17B1 in bladder cancer metastasis and invasion, suggesting its potential as a novel therapeutic target.

The utilisation of aluminium-based silicon carbide composites (SiCp/Al) is on the rise. However, during the grinding process, where abrasive particles compel SiC particles into the aluminium matrix, stress concentration occurs near the interface between the two phases. This phenomenon results in adverse surface deformation accompanied by residual compressive stress (RCS). Consequently, a pulsed laser-ultrasonic-assisted grinding method (PL-UAG) has been proposed. The effectiveness of the method is verified through grinding experiments. Moreover, the influence process of the thermal effect of pulsed laser and the evolution mechanism of microscopic RS near the SiCp/Al two-phase interface are revealed through molecular dynamics simulation. The experimental results show that the surface RCS of SiCp/Al gradually decreases and transforms into residual tensile stress (RTS) with the increase of laser power. The RCS increases with the grinding depth. The RCS is reduced to 17 Mpa and the surface roughness Sa value is reduced to 0.110 μm with the laser power is 40 W and the grinding depth is 1 μm. The simulation results show that the energy dissipation process of pulsed laser helps to reduce thermal deformation and damage. The laser-induced thermal effect reduces the deformation of the aluminium matrix caused by particle extrusion and inhibits the formation and slip of dislocations in the aluminium matrix. In addition, the ultrasonic shock effect effectively weakens the RTS generated by the laser.

The present study aimed to observe the combined effect of auricular pressure bean and compound tung leaf burn oil on postoperative incision healing in patients who have undergone circumcision. Total 160 patients who have undergone circumcision with disposable circumcision anastomosis at The First Affiliated Hospital of Nanchang University between August 2023 and October 2023, were recruited as participants for the study. They were divided into two groups, i.e., the control group and the observation group, using the randomised numerical table method. Each group consisted of 80 participants. The control group had received standard postoperative care, whereas the observation group had received additional treatment, i.e., the application of auricular pressure beans along with compound tung leaf burn oil along with routine care. Comparative analyses performed for various parameters such as postoperative 24-h pain score, initial changes in pain scores, duration of oedema subsidence, time of anastomotic nail dislodgement, the manual removal rate of anastomotic nails, incision healing time, the incidence of complications, and patient satisfaction statistically significant difference (p < 0.05) were observed in all parameters except the manual removal rate of anastomotic nails and the complication rate. In these two parameters, no statistically significant difference (p > 0.05) was observed. The application of auricular pressure bean along with compound tung leaf burn oil in patients who had undergone circumcision can significantly reduce the postoperative oedema duration, accelerate anastomotic nail removal and incision healing, reduce post-circumcision pain, and effectively promote overall patient recovery, thereby improving patient satisfaction.

Abstract The time-varying temperature distributions on bridge structures may remarkably change structural performance, which may result in differential strain/stress responses on structural members compared with the design conditions. Therefore, it is crucial to have a comprehensive understanding of temperature distributions and its effects on bridges. In this study, taking advantage of structural health monitoring technology, 1-year field monitoring data collected from a long-span suspension bridge were used to investigate the temperature distributions and their effects on the steel box girder. Specifically, the distributions and probability statistics of temperatures on the top and bottom plates were firstly analyzed. Based on which, the transverse and vertical temperature differences on the box girder were further examined, moreover, the representative values of temperature differences for various return periods were calculated by exceedance probability method. At end, a temperature prediction method was proposed to simulated the temperature field distributions during bridge life cycle, to provide substantial temperature data for estimating future operation condition. The results of this study were beneficial to structural evaluation of in-service bridges to ensure their serviceability and integrity in the life cycle.

Abstract Background Mucopolysaccharidosis type I (MPS‐I) is a rare autosomal recessive genetic lysosomal storage disorder that is caused by pathogenic variants of the α‐L‐iduronidase (IDUA) gene. This study aimed to identify the genetic causes of MPS‐I in a Chinese patient and construct a minigene of IDUA to analyze its variants upon splicing. Methods Whole‐exome sequencing (WES) and Sanger sequencing were used to confirm the potential causative variants. Single‐nucleotide polymorphism (SNP) array was subsequently performed to confirm uniparental disomy (UPD). Minigene assay was performed to analyze the effect on splicing of mRNA. We meanwhile explored the conservative analysis and protein homology simulation. Results A novel homozygous splicing mutation of IDUA, c.159‐9T>A, was identified in an individual presenting with overlapping features of MPS‐I. Interestingly, only the father and sisters, but not the mother, carried the variant in a heterozygous state. WES and SNP array analyses validated paternal UPD on chromosome 4. Minigene splicing revealed two aberrant splicing events: exon 2 skipping and intron 1 retention. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. Conclusions This study describes a rare autosomal recessive disorder with paternal UPD of chromosome 4 leading to the homozygosity of the IDUA splicing variant in patients with MPS‐I for the first time. This study expands the variant spectrum of IDUA and provides insights into the splicing system, facilitating its enhanced diagnosis and treatment.

Abstract Background Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. Method We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. Results 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09–1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17–2.51) in 1975–1979 to 0.99(0.89–1.1) in 2015–2019 (Ptrend 0.05). The cumulative suicide mortality during 1975–1994 was distinctly higher than in 1995–2019(P

Abstract Background This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive. Methods This study was cross-sectional, and the data were obtained from the 2011–2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis. Results Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19–0.47, P

Abstract The key role of RNA-binding proteins (RBPs) in posttranscriptional regulation of gene expression is intimately tied to their subcellular localization. Here, we show a subcellular-specific RNA labeling method for efficient enrichment and deep profiling of nuclear and cytoplasmic RBPs. A total of 1221 nuclear RBPs and 1333 cytoplasmic RBPs were enriched and identified using nuclear/cytoplasm targeting enrichment probes, representing an increase of 54.4% and 85.7% compared with previous reports. The probes were further applied in the omics-level investigation of subcellular-specific RBP-RNA interactions upon ferroptosis induction. Interestingly, large-scale RBPs display enhanced interaction with RNAs in nucleus but reduced association with RNAs in cytoplasm during ferroptosis process. Furthermore, we discovered dozens of nucleoplasmic translocation candidate RBPs upon ferroptosis induction and validated representative ones by immunofluorescence imaging. The enrichment of Tricarboxylic acid cycle in the translocation candidate RBPs may provide insights for investigating their possible roles in ferroptosis induced metabolism dysregulation.

Abstract Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1’s effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.

Background: Studies have shown that the stimulator of interferon genes (STING) is critical in tumorigenesis, and development. This study aimed to investigate the immune profile and prognostic significance of STING-mediated immune senescence in bladder cancer (BLCA). Methods: We identified differential genes between tumor and normal tissue based on the Cancer Genome Atlas database, and used consensus clustering to identify BLCA subtypes. The genes most associated with overall survival were screened by further analysis and used to construct risk models. Then, comparing the immune microenvironment, tumor mutational load (TMB), and microsatellite instability (MSI) scores between different risk groups. Eventually, a nomogram was constructed based on clinical information and risk scores. The model was validated using receiver operating curves (ROC) and calibration plots. Results: We identified 160 differential genes, including 13 genes most associated with prognosis. Three subtypes of bladder cancer with different clinical and immunological features were identified. Immunotherapy was more likely to benefit the low-risk group, which had higher TMB and MSI scores. The nomogram was found to be highly predictive based on ROC analysis and calibration plots. Conclusion: The risk model and nomogram not only predict the prognosis of BLCA patients but also can guide the treatment.

Abstract Purpose To investigate prognostic values of prostatic urethra involvement (PUI) and construct a prognostic model that estimates the probability of cancer-specific survival for T1 bladder cancer patients. Method and materials We investigated the national Surveillance, Epidemiology, and End Results (SEER) database (2004–2015) to get patients diagnosed with T1 bladder cancer. An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Kaplan–Meier method with the log-rank test was applied to assess cancer-specific survival (CSS) and overall survival (OS). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were performed. All patients were randomly divided into the development cohort and validation group at the ratio of 7:3. The performance of the model was internally validated by calibration curves and the concordance index (C-index). Results The PUI group had a lower survival rate of both CSS and overall survival OS before and after PSM when compared to non-involved patients (All P

Abstract Background Androgen receptor (AR) activation and repression dual-functionality only became known recently and still remains intriguing in prostate cancer (PCa). MYC is a prominent oncogene that functionally entangles with AR signaling in PCa. Further exploration of AR regulatory mechanisms on MYC gene transcription bears clinical and translation significance. Methods Bioinformatics analysis of PCa cell line and clinical RNA-Seq and ChIP-Seq (chromatin immunoprecipitation-sequencing) datasets to anchor interactions of AR and MYC transcriptional networks. ChIP-qPCR and 3C (chromosome conformation capture) analyses to probe MYC distal regulation by AR binding sites (ABSs). CRISPR/Cas9-mediated genome-editing to specify functions of ABS within the 8q24-MYC locus on androgen-mediated MYC transcription. Global FoxA1 and HoxB13 distribution profiling to advance AR transcriptional mechanisms. Results Here we recognize AR bi-directional transcription mechanisms by exploiting the prominent 8q24-MYC locus conferring androgen hyper-sensitivity. At ~ 25 Kb downstream of the MYC gene, we identified an undefined ABS, P10. By chromatin analyses, we validated androgen-dependent spatial interaction between P10 and MYC-Promoter (MYC-Pro) and temporal epigenetic repression of these MYC-proximal elements. We next designed a CRISPR/Cas9-mediated double genomic knock-out (KO) strategy to show that P10-KO slightly lessened androgen-elicited MYC transrepression in LNCaP-AR cells. In similar genomic editing assays, androgen-mediated MYC repression became slightly deepened upon KO of P11, an ABS in the PVT1 gene locus highly enriched in AR-binding motifs and peaks. We also investigated multiple ABSs in the established PCAT1 super-enhancer that distally interacts with MYC-Pro for transactivation, with each KO pool consistently shown to relieve androgen-elicited MYC repression. In the end, we systemically assessed androgen effects in the 8q24-MYC locus and along PCa genome to generalize H3K27ac and BRD4 re-distribution from pioneer factors (FoxA1 and HoxB13) to AR sites. Conclusion Together, we reconciled these observations by unifying AR dual-functions that are mechanistically coupled to and equilibrated by co-factor redistribution. Graphical Abstract

Background: Studies have shown that glucocorticoid receptor (GR) has inconsistent effects on the proliferation of prostate cancer cells, we found dexamethasone inhibited the proliferation of androgen receptor-negative prostate cancer cells, but the underlying mechanisms remain to be illustrated. Methods: GR expression and its prognosis role were analyzed based on the TCGA dataset. Bioinformatic analysis was performed to identify the candidate of GR downstream, which includes FOXO3a. After overexpressing FOXO3a in PC-3 cells, cell counting kit-8 (CCK-8) and migration assays were performed to evaluate cell proliferation and migration ability. Regulation of FOXO3a on GAS5 was also analyzed by JASPAR and PCR. Results: GR had low expression in prostate cancer and predicted poor prognosis. FOXO3a was identified as the downstream of GR to inhibit the proliferation of prostate cancer cells. Moreover, FOXO3a directly induces GAS5 expression, forming the GR-FOXO3a-GAS5 signaling pathway. Conclusion: Our study showed that GR played a role as a tumor suppressor gene in androgen receptor-negative prostate cancer cells via the GR-FOXO3a-GAS5 axis. Our results suggested patients with prostate cancer should be classified and develop a treatment plan according to the expression of AR and GR.

Background COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated. Methods We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases. Results We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan. Conclusion This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.

BackgroundDARS2 is a pivotal member of the Aminoacyl-tRNA synthetases family that is critical for regulating protein translation. However, the biological role of DARS2 in bladder cancer remains elusive.MethodsWe analyzed the correlation between DARS2 expression and prognosis, tumor stage, and immune infiltration in bladder cancer using The Cancer Genome Atlas (TCGA) database. We validated findings in clinical samples from The First Affiliated Hospital of Nanchang University and explored the biological functions of DARS2 using cell and animal models.ResultsWe found DARS2 to be upregulated in bladder cancer, associated with tumor progression and poor prognosis. Immune infiltration analysis suggested that DARS2 may facilitate immune evasion by modulating PD-L1. Cell and animal experiments validated that DARS2 knockdown and overexpress can inhibit or increase cancer cell proliferation, metastasis, tumorigenesis, immune escape, and PD-L1 levels.ConclusionsOur study reveals DARS2 as a potential prognostic biomarker and immunotherapy target in BLCA.

Background: CSMD2 has been reported as a potential prognostic factor in several cancers. However, whether CSMD2 affects bladder cancer (BC) remains unclear. Methods: Public data were obtained from the TCGA (https://cancergenome.nih.gov) databases. CSMD2expression and its prognostic value were analyzed using bioinformatics methods. CSMD2 mRNA level in patients with BC and BC cell lines was evaluated via quantitative reverse transcriptase polymerase chain reaction. CSMD2 protein level in patients with BC was evaluated via immunohistochemistry. BC cell lines T24 and UMUC-3 were selected for loss-of-function assays targeting CSMD2. Cell viability was determined by CCK8 and clone formation experiments. Cell migration and invasion were evaluated using Transwell assays. Furthermore, the transcriptome of UMUC-3 with CSMD2 knockdown was sequenced to analyze potential signaling network pathways. Finally, the TIMER2.0 database was employed to identify the correlation between CSMD2 and immune cells in the tumor microenvironment. Results: CSMD2 expression was up-regulated in BC tissues compared to adjacent tissues. High CSMD2 expression was associated with poor survival and could serve as an independent predictor for survival in patients with BC. Furthermore, down-regulation of CSMD2 notably restrained the viability, migration, and invasion abilities of T24 and UMUC-3 cells. Moreover, transcriptomic sequencing after CSMD2 knockdown in UMUC-3 cells revealed its involvement in the regulation of the malignant phenotype in BC. Finally, public databases suggest a connection between CSMD2 and immune cell infiltration in BC. Conclusions: These findings suggest that CSMD2 may promote proliferation and tumorigenicity, and could represent a potential target for improving the prognosis of BC.

Water–air two-phase flow has been the theoretical basis of traditional building drainage systems. However, with the popularization of water saving devices, more research investigations need to be performed on the impact of solid waste on drainage systems. Through experiments under the solid waste scenario, the effects of drainage volume, diameter, and slope of the pipeline on the hydraulic performances of the horizontal main drain were investigated. The results showed that the drainage volume, diameter, and slope of the pipeline did not affect the location of the hydraulic jump on the horizontal main drain. The heights of the hydraulic jump were proportional to the discharge volumes and diameters of the pipeline, but inversely proportional to the slopes of the pipeline. The depth ratio was mainly responsible for the change of positive pressure value in the horizontal main drain. The depth ratios were proportional to the drainage volumes and inversely proportional to the diameters and slopes of the pipeline. The final deposition distances of solid wastes in the horizontal main drain were proportional to the discharge volumes and the pipeline slopes. The self-cleaning lengths of the clear water were 1.2∼1.6 times of the real final deposition distances of solid wastes. HIGHLIGHTS The change of depth ratio caused the variation of positive pressure in horizontal main drain.; The location of hydraulic jump was not affected by the drainage volume, the diameter or the slope.; The height of the hydraulic jump was affected by the drainage volume, the diameter and the slope.; The depth ratio was affected by the drainage volume, the diameter and the slope.; The final deposition distance of solid wastes was affected by the drainage volume, the diameter and the slope.;

Abstract Objectives To construct and validate unfavorable pathology (UFP) prediction models for patients with the first diagnosis of bladder cancer (initial BLCA) and to compare the comprehensive predictive performance of these models. Materials and Methods A total of 105 patients with initial BLCA were included and randomly enrolled into the training and testing cohorts in a 7:3 ratio. The clinical model was constructed using independent UFP‐risk factors determined by multivariate logistic regression (LR) analysis in the training cohort. Radiomics features were extracted from manually segmented regions of interest in computed tomography (CT) images. The optimal CT‐based radiomics features to predict UFP were determined by the optimal feature filter and the least absolute shrinkage and selection operator algorithm. The radiomics model consist with the optimal features was constructed by the best of the six machine learning filters. The clinic‐radiomics model combined the clinical and radiomics models via LR. The area under the curve (AUC), accuracy, sensitivity, specificity, positive and negative predictive value, calibration curve and decision curve analysis were used to evaluate the predictive performance of the models. Results Patients in the UFP group had a significantly older age (69.61 vs. 63.93 years, p = 0.034), lager tumor size (45.7% vs. 11.1%, p = 0.002) and higher neutrophil to lymphocyte ratio (NLR; 2.76 vs. 2.33, p = 0.017) than favorable pathologic group in the training cohort. Tumor size (OR, 6.02; 95% CI, 1.50–24.10; p = 0.011) and NLR (OR, 1.50; 95% CI, 1.05–2.16; p = 0.026) were identified as independent predictive factors for UFP, and the clinical model was constructed using these factors. The LR classifier with the best AUC (0.817, the testing cohorts) was used to construct the radiomics model based on the optimal radiomics features. Finally, the clinic‐radiomics model was developed by combining the clinical and radiomics models using LR. After comparison, the clinic‐radiomics model had the best performance in comprehensive predictive efficacy (accuracy = 0.750, AUC = 0.817, the testing cohorts) and clinical net benefit among UFP‐prediction models, while the clinical model (accuracy = 0.625, AUC = 0.742, the testing cohorts) was the worst. Conclusion Our study demonstrates that the clinic‐radiomics model exhibits the best predictive efficacy and clinical net benefit for predicting UFP in initial BLCA compared with the clinical and radiomics model. The integration of radiomics features significantly improves the comprehensive performance of the clinical model.

Abstract Background TUBA1C is an α-tubulin isoform involved in mitosis, and its dysregulation has been implicated in tumor progression. There is still no clear understanding of its role in bladder urothelial carcinoma (BLCA). Methods This study examined the differential expression of TUBA1C and its prognostic significance in bladder cancer based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and also assessed the correlation of TUBA1C expression level with immune cell infiltration and immune checkpoint gene expression levels and the half-inhibitory concentration (IC50) of different chemotherapeutic agents. Immunotherapy response was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We detected TUBA1C expression in BLCA cells using PCR and Western blotting. Functional assays, including CCK-8, colony formation, transwell, apoptosis and cell cycle assays, were also performed to assess the oncogenic role of TUBA1C in BLCA. Result In three independent public cohorts, TUBA1C was significantly upregulated in bladder tumor tissues, and high TUBA1C expression in bladder cancer was associated with a poorer outcome than low expression. TUBA1C was an independent prognostic risk factor for bladder cancer, and numerous immune checkpoint genes and infiltrating immune cells were associated with TUBA1C. TIDE analysis revealed that TUBA1C showed great potential for predicting the immunotherapy response in bladder cancer patients. In addition, drug sensitivity analysis revealed that high TUBA1C expression indicated sensitivity to multiple chemotherapeutic agents. Functional assays revealed that silencing TUBA1C significantly inhibited the proliferation, migration and invasion of BLCA cells and induced apoptosis and cell cycle arrest. Conclusion The overexpression of TUBA1C in bladder cancer predicts a poor prognosis and may also be a potential immunotherapeutic target. As a prognostic marker, TUBA1C influences tumor progression by regulating the cell cycle.

The accurate characterization of typhoon wind profile properties is of great importance in the field of wind engineering and wind design of high-rise structures. In this paper, the average typhoon wind profile characteristics are investigated using the 930 m height measurement data of Typhoon Lekima 2019 obtained from the observations of the mobile acoustic profiling radar deployed in the coastal area. Specifically, this paper adopts a cohesive hierarchical cluster analysis method to classify the mean wind profiles of Super Typhoon Lekima 2019, and the optimal number of clusters is obtained as two classes by the profile coefficient with the sum of squares of clustering errors, the Calinski–Harabasz index, and the Davies–Bouldin index, and the two classes of typical wind profiles are named as cluster 1 type and cluster 2 type. The model fitting analysis of the two types of typical wind profiles was carried out in the height range of 0~300 m after classification, and the effects of fitting the cluster 1-type mean wind profiles with the Vickery model and the Snaiki and Wu model and the cluster 2-type mean wind profiles with the Power-law model, the Log-law model, and the Deaves–Harris and Gryning models were discussed. The results show that the cohesive hierarchical cluster analysis method used in this paper can effectively categorize the mean typhoon profiles. In addition, this paper has some reference significance for future research on the characteristics of measured typhoon wind profiles and engineering applications such as the wind-resistant design of high-rise structures.

Surfactants play a pivotal role in daily life owing to their commendable performance. The outbreak of the COVID-19 pandemic notably escalated surfactant usage. Upon entering building drainage systems with wastewater, surfactants profoundly influence hydraulic performance, an aspect that has garnered limited scholarly attention. This study employs an equally proportioned drainage test device to meticulously examine the variances in physical properties between surfactants, such as sodium dodecyl benzene sulfonate (SDBS) and alkyl ethoxylate-9 (AEO-9), and their repercussions on the hydraulic dynamics of building drainage horizontal main drains. Our findings reveal that the introduction of surfactants leads to the following: (1) an augmentation in water velocity and deposition distances of the solid simulant in the building drainage horizontal main drain with concentrations exacerbating this effect. The deposition distance of the solid simulation surged by up to 527% under experimental conditions compared to no surfactant; (2) there was a suppression of hydraulic jump and full degree of the horizontal main drain, with the concentration amplifying this suppression; and (3) an exacerbation of positive pressure in the horizontal main drain was found with increasing concentration, reaching a staggering 235.3% elevation compared to no surfactant. Moreover, SBDS foam outperformed AEO-9, demonstrating a 17.70–36.04% higher positive pressure in the horizontal main pipes. SBDS exhibits lower starting and ultimate viscosity, along with smaller colloid particle sizes, resulting in a 0.9–2.0% reduction in hydraulic jump and full degree. However, its inferior drag-reduction capability leads to a 17.48–36.44% decrease in the final deposition distances of solid simulant in the building drainage horizontal main drain compared to AEO-9.

Many cities in coastal areas are prone to typhoon disasters due to their location on the Pacific storm path, and the direct effect of catastrophic winds can lead to the destruction of low-rise buildings and severe damage to high-rise structures. The purpose of this study was to enhance the understanding of boundary layer wind profiles of strong typhoons in coastal areas and reduce property losses and casualties caused by wind disasters. Based on the field measurements of wind profile acoustic radar in coastal areas, the variation characteristics of the boundary layer wind profile during the passage of super typhoon Lekima were first studied in depth, and the evolution law of the typhoon boundary layer profile was summarized. Then, the effects of typhoon horizontal structure, topography, wind speed, and time distance on the characteristics of the typhoon profile were discussed, respectively. Finally, the evolution characteristics of wind profile parameters were obtained by fitting three wind profile theoretical models. Due to the strong variability of typhoon profile morphology, the theoretical model of wind profile is only applicable to the wind profile from the bottom to the low-level jet height of typhoons, while wind parameters are closely related to the spatial location of the typhoon wind field.

Recently, the frequent occurrence of droughts has caused a serious impact on vegetation growth and progression. This research is based upon the normalized difference vegetation index (NDVI) from 2001 to 2020. The correlation between the NDVI and standardized precipitation evapotranspiration index (SPEI) at disparate time scales was used to assess the response of vegetation growth to drought in the Yinshanbeilu region. The drought levels of SPEI1, SPEI3, SPEI6, and SPEI12 increased prominently in the eastern region of the country, while the NDVI decreased significantly from east to west in spring, summer, and autumn but was reversed in the winter. The area with an upward trend (33.86%) was slightly lower than that with a downward trend (66.14%). The correlation coefficients between the NDVI and SPEI over the entire year increased with the SPEI timescale. The elevated values were concentrated in the southeastern and western regions of the survey region. Additionally, the best correlation timescales were SPEI6 and SPEI12. Grassland was the most sensitive vegetation type to the SPEI response in the NDVI. The correlation coefficients of NDVI and SPEI1–12 were 0.313, 0.459, 0.422, and 0.406. Both spring and summer were more responsive to SPEI12, whereas autumn and winter were more responsive to SPEI3. The correlation of disparate time scales exhibited complex soil texture features with respect to different seasonal scales, and the soil texture showed a strong response to vegetation in both summer and autumn. Loam, sandy loam, and silty loam all exhibited the highest response to SPEI12, with coefficients of 0.509, 0.474, and 0.403, respectively.

Abstract There is evidence from multiple studies that dysregulation of the Eyes Absent (EYA) protein plays multiple roles in many cancers. Despite this, little is known about the prognostic significance of the EYAs family in clear cell renal cell carcinoma (ccRCC). We systematically analyzed the value of EYAs in Clear Cell Renal Cell Carcinoma. Our analysis included examining transcriptional levels, mutations, methylated modifications, co-expression, protein–protein interactions (PPIs), immune infiltration, single-cell sequencing, drug sensitivity, and prognostic values. We based our analysis on data from several databases, including the Cancer Genome Atlas database (TCGA), the Gene Expression Omnibus database (GEO), UALCAN, TIMER, Gene Expression Profiling Interactive Analysis (GEPIA), STRING, cBioPortal and GSCALite. In patients with ccRCC, the EYA1 gene was significantly highly expressed, while the expression of EYA2/3/4 genes showed the opposite trend. The level of expression of the EYA1/3/4 gene was significantly correlated with the prognosis and clinicopathological parameters of ccRCC patients. Univariate and multifactorial Cox regression analyses revealed EYA1/3 as an independent prognostic factor for ccRCC, establishing nomogram line plots with good predictive power. Meanwhile, the number of mutations in EYAs was also significantly correlated with poor overall survival (OS) and progression-free survival (PFS) of patients with ccRCC. Mechanistically, EYAs genes play an essential role in a wide range of biological processes such as DNA metabolism and double-strand break repair in ccRCC. The majority of EYAs members were related to the infiltration of immune cells, drug sensitivity, and methylation levels. Furthermore, our experiment confirmed that EYA1 gene expression was upregulated, and EYA2/3/4 showed low expression in ccRCC. The increased expression of EYA1 might play an important role in ccRCC oncogenesis, and the decreased expression of EYA3/4 could function as a tumor suppressor, suggesting EYA1/3/4 might serve as valuable prognostic markers and potential new therapeutic targets for ccRCC.

Abstract Background Renal cell carcinoma (RCC) survival has improved due to recent developments in RCC treatment. Therefore, other co-morbid conditions may have a more critical role. This study aims to explore the common causes of death in patients with RCC to improve the management and survival of RCC. Method We used the Surveillance, Epidemiology, and End Results (SEER) (1992–2018) database to get patients with RCC. We calculated the percentage of total deaths of six kinds of the cause of death (COD) and the cumulative incidence of death for each selected cause over survival time. The joinpoint regression was utilized to present the trend of mortality rate by COD. Results We enrolled 107,683 cases with RCC. RCC was the leading cause of death in patients with RCC [25376(48.3%)], followed by cardiovascular diseases [9023(17.2%)], other cancers [8003 (15.2%)], other non-cancer diseases [4195 (8%)], non-disease cause [4023 (7.7%)], and respiratory diseases [1934 (3.6%)]. The proportion of patients who died of RCC decreased gradually over survival time, and this value decreased from 69.71% in 1992–1996 to 38.96% in 2012–2018. The non-RCC cause mortality rate showed an increasing trend, whereas a slight decrease was observed in RCC specific mortality rate. The distribution of such conditions varied across different patient populations. Conclusion RCC was still the primary COD of patients with RCC. However, non-RCC cause death was increasingly important among RCC patients in recent two decades. Cardiovascular disease and other cancers were crucial co-morbidities that required significant attention in the management of RCC patients.

BackgroundHypoxia and metabolism are closely correlated with the progression of cancer. We aimed to construct a combined hypoxia- and metabolism-related genes (HMRGs) prognostic signature to predict survival and immunotherapy responses in patients with clear cell renal cell carcinoma (ccRCC).MethodsThe RNA-seq profiles and clinical data of ccRCC were acquired from the TCGA and the ArrayExpress (E-MTAB-1980) databases. Least absolute shrinkage and selection operator (LASSO) and univariate and multivariate Cox regression analyses were applied to establish a prognostic signature. The E-MTAB-1980 cohort was selected for validation. The effectiveness and reliability of the signature were further evaluated by Kaplan–Meier (K-M) survival and time-dependent receiver operating characteristic (ROC) curves. Further analyses, including functional enrichment, ssGSEA algorithm, CIBERSORT algorithm, and expression of immune checkpoints, were explored to investigate immune status and immunotherapy responses.ResultsWe constructed a prognostic eight-gene signature with IRF6, TEK, PLCB2, ABCB1, TGFA, COL4A5, PLOD2, and TUBB6. Patients were divided into high-risk and low-risk groups based on the medium-risk score. The K-M analysis revealed that patients in the high-risk group had an apparently poor prognosis compared to those in the low-risk group in the TCGA (p < 0.001) and E-MTAB-1980 (p < 0.005). The area under ROC curve (AUC) of the prognostic signature was 0.8 at 1 year, 0.77 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.82 at 1 year, 0.74 at 3 years, and 0.75 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis confirmed the risk score as a separate prognostic factor in ccRCC patients (p < 0.001). The results of ssGSEA showed not only a high degree of immune cell infiltration but also high scores of immune-related functions in the high-risk group. The CIBERSORT analysis further confirmed that the abundance of immune cells was apparently different between the two risk groups. The risk score was significantly correlated with the expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and programmed cell death protein 1 (PD-1).ConclusionThe HMRGs signature could be used to predict clinical prognosis, evaluate the efficacy of immunotherapy, and guide personalized immunotherapy in ccRCC patients.

The southeastern Tibetan Plateau, which profoundly affects East Asia by helping to maintain the stability of climate systems, biological diversity and clean water, is one of the regions most vulnerable to water erosion, wind erosion, tillage erosion, freeze–thaw erosion and overgrazing under global climate changes and intensive human activities. Spatial variations in soil erosion in terraced farmland (TL), sloping farmland (SL) and grassland (GL) were determined by the 137Cs tracing method and compared with spatial variations in soil organic carbon (SOC) and total nitrogen (total N). The 137Cs concentration in the GL was higher in the 0–0.03 m soil layer than in the other soil layers due to weak migration and diffusion under low precipitation and temperature conditions, while the 137Cs concentration in the soil layer of the SL was generally uniform in the 0–0.18 m soil layer due to tillage-induced mixing. Low 137Cs inventories appeared at the summit and toe slope positions in the SL due to soil loss by tillage erosion and water erosion, respectively, while the highest 137Cs inventories appeared at the middle slope positions due to soil accumulation under relatively flat landform conditions. In the GL, the 137Cs data showed that higher soil erosion rates appeared at the summit due to freeze–thaw erosion and steep slope gradients and at the toe slope position due to wind erosion, gully erosion, freeze–thaw erosion and overgrazing. The 137Cs inventory generally increased from upper to lower slope positions within each terrace (except the lowest terrace). The 137Cs data along the terrace toposequence showed abrupt changes in soil erosion rates between the lower part of the upper terrace and the upper part of the immediate terrace over a short distance and net deposition on the lower and toe terraces. Hence, tillage erosion played an important role in the soil loss at the summit slope positions of each terrace, while water erosion dominantly transported soil from the upper terrace to the lower terrace and resulted in net soil deposition on the flat lower terrace. The SOC inventories showed similar spatial patterns to the 137Cs inventories in the SL, TL and GL, and significant correlations were found between the SOC and 137Cs inventories in these slope landscapes. The total N inventories showed similar spatial patterns to the inventories of 137Cs and SOC, and significant correlations were also found between the total N and 137Cs inventories in the SL, TL and GL. Therefore, 137Cs can successfully be used for tracing soil, SOC and total N dynamics within slope landscapes in the southeastern Tibetan Plateau.

Abstract Background Numerous studies have shown that local therapy can improve long-term survival in patients with metastatic prostate cancer. However, it is unclear which patients are the potential beneficiaries. Methods We obtained information on prostate cancer patients from the Surveillance, Epidemiology, and End Results database and divided eligible patients into the local treatment group and non-local treatment group. Propensity score matching (PSM) was used to reduce the influence of confounding factors. In the matched local treatment (LT) group, if the median overall survival time (OS) was longer than the Nonlocal treatment (NLT) group, it was defined as a benefit group, otherwise, it was a non-benefit group. Then, univariate and multivariate logistic regression were used to screen out predictors associated with benefits, and a nomogram model was constructed based on these factors. The accuracy and clinical value of the models were assessed through calibration plots and decision curve analysis. Results The study enrolled 7255 eligible patients, and after PSM, each component included 1923 patients. After matching, the median OS was still higher in the LT group than in the NLT group [42 (95% confidence interval: 39–45) months vs 40 (95% confidence interval: 38–42) months, p = 0.03]. The independent predictors associated with benefit were age, PSA, Gleason score, T stage, N stage, and M stage. The nomogram model has high accuracy and clinical application value in both the training set (C-index = 0.725) and the validation set (C-index = 0.664). Conclusions The nomogram model we constructed can help clinicians identify patients with potential benefits from LT and formulate a reasonable treatment plan.

The microstructure, corrosion resistance, and phase-transition process of micro-arc oxidation (MAO) coatings prepared on LaFe11.6Si1.4 alloy surfaces in different electrolyte systems were systematically investigated. Research has demonstrated that various electrolyte systems do not alter the main components of the coatings. However, the synergistic action of Na2CO3 and Na2B4O7 more effectively modulated the ionization and chemical reactions of the MAO process and accelerated the formation of α-Al2O3. Moreover, the addition of Na2CO3 and Na2B4O7 improved the micromorphology of the coating, resulting in a uniform coating thickness and good bonding with the LaFe11.6Si1.4 substrate. The dynamic potential polarization analysis was performed in a three-electrode system consisting of a LaFe11.6Si1.4 working electrode, a saturated calomel reference electrode, and a platinum auxiliary electrode. The results showed that the self-corrosion potential of the LaFe11.6Si1.4 alloy without surface treatment was −0.68 V, with a current density of 8.96 × 10−6 A/cm2. In contrast, the presence of a micro-arc electrolytic oxidation coating significantly improved the corrosion resistance of the LaFe11.6Si1.4 substrate, where the minimum corrosion current density was 1.32 × 10−7 A/cm2 and the corrosion potential was −0.50 V. Similarly, after optimizing the MAO electrolyte with Na2CO3 and Na2B4O7, the corrosion resistance of the material further improved. Simultaneously, the effect of the coatings on the order of the phase transition, latent heat, and temperature is negligible. Therefore, micro-arc oxidation technology based on the in situ growth coating of the material surface effectively improves the working life and stability of La(Fe, Si)13 materials in the refrigeration cycle, which is an excellent alternative as a protection technology to promote the practical process of magnetic refrigeration technology.

The current paper verifies the asynchronous H∞ control and optimization problem for flight vehicles with a time-varying delay. The nonlinear dynamic model and Jacobian linearization establish the flight vehicle’s switched model. An asynchronous H∞ tracking controller is designed, considering the existing asynchronous switching between the controllers and corresponding subsystems. In order to promote transient efficiency, the tracking controller comprises the model-based part and the learning-based part. The model-based part guarantees stability and prescribed efficiency, and the learning-based part compensates for undesirable uncertainties. The multiple Lyapunov function (MLF) and mode-dependent average dwell time (MDADT) methods are utilized to guarantee stability and the specified attenuation efficiency. The existing conditions and the solutions of model-based sub-controllers are represented by linear matrix inequalities (LMIs). The deep Q learning (DQL) algorithm provides the learning-based part. Different from the conventional method, the controller parameters are scheduled online. Therefore, robustness, stability, and dynamic efficiency can be met simultaneously. A numerical example illustrates the efficiency and advantage of the presented approach.

Drought refers to a meteorological disaster that results in insufficient soil moisture due to a long-term lack of rainfall and disrupts the moisture balance of crops. Yinshanbeilu in Inner Mongolia is an arid and semi-arid region, and the onset of drought and its subsequent transmission is a key challenge in water resource management. This study takes Yinshanbeilu as the study area, analyses the changing characteristics of multi-timescale drought from 1971 to 2020 based on the Standardised Precipitation Index (SPI), and analyses the stochasticity and stability of the drought by using a cloud model. Finally, the cross-wavelet transform method and Pearson’s test are used to explore the correlation between atmospheric circulation factors, PRE and PET, and drought. The results indicate that (1) on the annual scale, the frequency of drought in Yinshanbeilu mainly ranges from 22% to 28%, with a high frequency of light droughts, a low frequency of severe droughts, a high frequency of droughts in the east and west, and a low frequency of droughts in the north and south; on the seasonal scale, the frequency of droughts in winter is the highest, with a rate of 34.6%, and the lowest frequency of droughts is in autumn, with a rate of 28.3%. (2) There is a decreasing trend in Entropy (En) and Hyper-Entropy (He), and an increasing trend in Expectation (Ex) for the inter-annual SPI-12 cloud model. Spatially, Ex and He are negatively correlated, while En and He are positively correlated. The inter-annual variation in cloud eigenvalues is greater than the inter-site variation, so the cloud model better reflects the spatial stochasticity and stability of regional inter-annual SPI. For the seasonal-scale SPI-3 cloud model, Ex is smaller in all seasons, En is also smaller, and He is larger. (3) Sunspot, PRE (precipitation), and PET (Potential Evapotranspiration) are all positively correlated with SPI and have the highest correlation. This study reveals the characteristics and causes of variations of drought in Yinshanbeilu, which can be applied to future research areas related to regional drought risk management.

Background: Lung metastatic tumor (LM) is one of testicular germ cell tumors' most common metastatic sites. Our study aimed to develop a nomogram for predicting the risk of LM among patients with testicular germ cell tumors (TGCTs). Methods: Clinicopathological information of 4078 patients with TGCT between 2010 and 2015 was obtained from SEER. Univariate and multivariate logistic regression analyses were performed to identify risk factors for LM, and a nomogram was developed based on these factors. Calibration curves, area under the receiver operating curve (AUC), and decision curve analysis (DCA) were used to evaluate the accuracy and discrimination of the model. Results: Study participants included 4078 people with TGCTs, including 305 people with LM. They were randomly divided into two groups (training cohort = 2854 and validation cohort = 1224) at a ratio of 7:3. The following variables were incorporated in the nomogram: marital status, tumor histological type, T stage, brain metastasis, liver metastasis, lactate dehydrogenase (LDH), and chemotherapy. Besides, the AUC of it was 0.922 in the training cohort, while was 0.930 in the validation cohort. Training and validation cohort calibrations showed that the nomogram had excellent predictive abilities. DCA suggested it was more clinically relevant than the traditional TN staging. Conclusion: We have established a nomogram to predict the risk of LM in patients with TGCTs. Doctors and patients can use this nomogram to monitor and identify lung metastasis of tumors through active monitoring and follow-up.

ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients.

BackgroundBoth lactylation and m6A modification have important implications for the development of clear cell renal cell carcinoma (ccRCC), and we aimed to use crosstalk genes of both to reveal the prognostic and immunological features of ccRCC.MethodsOur first step was to look for lactylation-related genes that differed between normal and tumor tissues, and then by correlation analysis, we found the genes associated with M6A. Following that, ccRCC subtypes will be identified and risk models will be constructed to compare the prognosis and tumor microenvironment among different subgroups. A nomogram was constructed to predict the prognosis of ccRCC, and in vitro, experiments were conducted to validate the expression and function of key genes.ResultsWe screened 100 crosstalk genes and identified 2 ccRCC subtypes. A total of 11 prognostic genes were screened for building a risk model. we observed higher immune scores, elevated tumor mutational burden, and microsatellite instability scores in the high-risk group. Therefore, individuals classified as high-risk would derive greater benefits from immunotherapy. The nomogram’s ability to predict overall survival with a 1-year AUC of 0.863 demonstrates its significant practical utility. In addition, HIBCH was identified as a potential therapeutic target and its expression and function were verified by in vitro experiments.ConclusionIn addition to developing a precise prognostic nomogram for patients with ccRCC, our study also discovered the potential of HIBCH as a biomarker for the disease.

BackgroundOxidative stress plays a significant role in the tumorigenesis and progression of tumors. We aimed to develop a prognostic signature using oxidative stress-related genes (ORGs) to predict clinical outcome and provide light on the immunotherapy responses of clear cell renal cell carcinoma (ccRCC).MethodsThe information of ccRCC patients were collected from the TCGA and the E-MTAB-1980 datasets. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were conducted to screen out overall survival (OS)-related genes. Then, an ORGs risk signature was built by multivariate Cox regression analyses. The performance of the risk signature was evaluated with Kaplan-Meier (K-M) survival. The ssGSEA and CIBERSORT algorithms were performed to evaluate immune infiltration status. Finally, immunotherapy responses was analyzed based on expression of several immune checkpoints.ResultsA prognostic 9-gene signature with ABCB1, AGER, E2F1, FOXM1, HADH, ISG15, KCNMA1, PLG, and TEK. The patients in the high risk group had apparently poor survival (TCGA: p < 0.001; E-MTAB-1980: p < 0.001). The AUC of the signature was 0.81 at 1 year, 0.76 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.8 at 1 year, 0.82 at 3 years, and 0.83 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis proved the stable clinical prognostic value of the signature (TCGA cohort: HR = 1.188, 95% CI =1.142-1.236, p < 0.001; E-MTAB-1980 cohort: HR =1.877, 95% CI= 1.377-2.588, p < 0.001). Clinical features correlation analysis proved that patients in the high risk group were more likely to have a larger range of clinical tumor progression. The ssGSEA and CIBERSORT analysis indicated that immune infiltration status were significantly different between two risk groups. Finally, we found that patients in the high risk group tended to respond more actively to immunotherapy.ConclusionWe developed a robust prognostic signature based on ORGs, which may contribute to predict survival and guide personalize immunotherapy of individuals with ccRCC.

The Shuangjianzishan super-large Ag-Pb-Zn deposit is situated in the southern Great Xing’an Range (SGXR), which is part of the eastern Central Asian Orogenic Belt (CAOB) and the northeastern Xing’an-Mongolia Orogenic Belt (XMOB). The host rock of this deposit is the Dashizhai Formation, characterized by a widely distributed, extremely thick slate in the Shuangjianzishan basin. Petrographically, the slate contains secondary minerals such as secondary quartz, biotite, sphalerite, pyrite, galena, and chalcopyrite, in addition to primary quartz, feldspar, and rock fragment. The whole-rock geochemical analysis indicates that the slate was deposited in an oxygen-deficient shale basin, influenced by calcium-rich volcanic ash and magmatic-hydrothermal fluids. The mineralogical characteristics of sulfide minerals and the in-situ sulfur isotopic composition of pyrites suggest that the sulfide minerals were likely formed before the primary metallogenic epoch, indicating pre-enrichment of metals. The color variation from black to green observed in the drilling core of the slate is attributed to differences in feldspar content, with the denser “black” slate marking the metallogenic horizon. Based on previous research, it is inferred that the slate is a product of the post-orogenic extensional tectonic setting of the XMOB in the Late Carboniferous, and it underwent alteration by epithermal magmatic-hydrothermal fluids during the Mesozoic metallogenic episode.

BackgroundGlycyl-tRNA synthetase 1 (GARS1) belongs to the aminoacyl-tRNA synthetase family, playing a crucial role in protein synthesis. Previous studies have reported a close association between GARS1 and various tumors. However, the role of GARS1 in human cancer prognosis and its impact on immunology remain largely unexplored.MethodsIn this study, we comprehensively analyzed GARS1 expression at the mRNA and protein levels, examined genetic alterations, and assessed its prognostic implications in pan-cancer, with a specific emphasis on the immune landscape. Furthermore, we investigated the functional enrichment of genes related to GARS1 and explored its biological functions using single-cell data. Finally, we conducted cellular experiments to validate the biological significance of GARS1 in bladder cancer cells.ResultsIn general, GARS1 expression was significantly upregulated across multiple cancer types, and it demonstrated prognostic value in various cancers. Gene Set Enrichment Analysis (GSEA) revealed the association of GARS1 expression with multiple immune regulatory pathways. Moreover, GARS1 exhibited significant correlations with immune infiltrating cells (such as DC, CD8+T cells, Neutrophils, and Macrophages), immune checkpoint genes (CD274, CD276), and immune regulatory factors in tumors. Additionally, we observed that GARS1 could effectively predict the response to anti-PD-L1 therapy. Notably, Ifosfamide, auranofin, DMAPT, and A-1331852 emerged as potential therapeutic agents for GARS1-upregulated tumors. Our experimental findings strongly suggest that GARS1 promotes the proliferation and migration of bladder cancer cells.ConclusionGARS1 holds promise as a potential prognostic marker and therapeutic target for pan-cancer immunotherapy, offering valuable insights for the development of more precise and personalized approaches to tumor treatment in the future.

BackgroundThe aim of this study was to develop a comprehensive and effective nomogram for predicting overall survival (OS) rates in postoperative patients with high-grade bladder urothelial carcinoma.MethodsPatients diagnosed with high-grade urothelial carcinoma of the bladder after radical cystectomy (RC) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. We randomly split (7:3) these patients into the primary cohort and the internal validation cohort. Two hundred eighteen patients from the First Affiliated Hospital of Nanchang University were collected as the external validation cohort. Univariate and multivariate Cox regression analyses were carried out to seek prognostic factors of postoperative patients with high-grade bladder cancer (HGBC). According to these significant prognostic factors, a simple-to-use nomogram was established for predicting OS. Their performances were evaluated using the concordance index (C-index), the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsThe study included 4,541 patients. Multivariate Cox regression analysis demonstrated that T stage, positive lymph nodes (PLNs), age, chemotherapy, regional lymph nodes examined (RLNE), and tumor size were correlated with OS. The C-index of the nomogram in the training cohort, internal validation cohort, and external validation cohort were 0.700, 0.717, and 0.681, respectively. In the training, internal validation, and external validation cohorts, the ROC curves showed that the 1-, 3-, and 5-year areas under the curve (AUCs) were higher than 0.700, indicating that the nomogram had good reliability and accuracy. The results of calibration and DCA showed good concordance and clinical applicability.ConclusionA nomogram was developed for the first time to predict personalized 1-, 3-, and 5-year OS in HGBC patients after RC. The internal and external validation confirmed the excellent discrimination and calibration ability of the nomogram. The nomogram can help clinicians design personalized treatment strategies and assist with clinical decisions.

PurposeMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier for patients in the prostate-specific antigen gray zone are to be developed and compared, identifying valuable predictors. Predictive models are to be integrated into actual clinical decisions.MethodsPatient information was collected from December 01, 2014 to December 01, 2022 from the Department of Urology, The First Affiliated Hospital of Nanchang University. Patients with a pathological diagnosis of prostate hyperplasia or prostate cancer (any PCa) and having a prostate-specific antigen (PSA) level of 4–10 ng/mL before prostate puncture were included in the initial information collection. Eventually, 756 patients were selected. Age, total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), fPSA/tPSA, prostate volume (PV), prostate-specific antigen density (PSAD), (fPSA/tPSA)/PSAD, and the prostate MRI results of these patients were recorded. After univariate and multivariate logistic analyses, statistically significant predictors were screened to build and compare machine learning models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier to determine more valuable predictors.ResultsMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier exhibit higher predictive power than individual metrics. The area under the curve (AUC) (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of the LogisticRegression machine learning prediction model were 0.932 (0.881–0.983), 0.792, 0.824, 0.919, 0.652, 0.920, and 0.728, respectively; of the XGBoost machine learning prediction model were 0.813 (0.723–0.904), 0.771, 0.800, 0.768, 0.737, 0.793 and 0.767, respectively; of the GaussianNB machine learning prediction model were 0.902 (0.843–0.962), 0.813, 0.875, 0.819, 0.600, 0.909, and 0.712, respectively; and of the LGBMClassifier machine learning prediction model were 0.886 (0.809–0.963), 0.833, 0.882, 0.806, 0.725, 0.911, and 0.796, respectively. The LogisticRegression machine learning prediction model has the highest AUC among all prediction models, and the difference between the AUC of the LogisticRegression prediction model and those of XGBoost, GaussianNB, and LGBMClassifier is statistically significant (p < 0.001).ConclusionMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier algorithms exhibit superior predictability for patients in the PSA gray area, with the LogisticRegression model yielding the best prediction. The aforementioned predictive models can be used for actual clinical decision-making.​

Objective: To explore the combined uses of central vein isolation-based laparoscopic technique and tubeless cardiovascular interventional technique (CVIT) in laparoscopic adrenalectomy. Methods: 31 subject patients with adrenal tumors were recruited and treated from January 2020 to November 2021. Regarding tumor size, the average transverse diameter of the adrenal tumor was (2.2 ± 1.0) cm and the average longitudinal diameter of the tumor was (3.1 ± 1.5) cm, respectively. All subject patients were operated on through the abdominal approach. The ''central vein isolation'' based laparoscopic technique was adopted to complete the operation. No drainage tube was placed in the patients. For this study, selected performance parameters, including the operation time, intraoperative bleeding, postoperative hospital stays, and postoperative complications were recorded and analyzed. Results: All the tumors were removed laparoscopically without any conversion to open surgery. All 31 recruited subjects were treated successfully with preservation of adrenocortical function. The mean operation time was 30 min (range from 25 to 63 min); the mean amount of intraoperative bleeding was approximately 3 mL (ranges from 0 to 10 mL); the mean postoperative hospital stay was 3 days (range from 2 to 6 days). Of note, no complications were recorded, such as adjacent organ injury, large vessel injury, infection, and secondary bleeding that occurred during and after the operation. Conclusion: The combined use of central-vein isolation laparoscopic technique and tubeless treatment ensures a facile, safe, and robust laparoscopic adrenalectomy operation in clinical practice.

Background Previous studies have confirmed the higher risk of bladder cancer (BC) and rectal cancer (RC) development among prostate cancer (PCa) patients receiving radiotherapy. In this study, we intend to explore the long-term trend in second BC and RC incidence among PCa patients undergoing radiotherapy. Method We identified first primary PCa patients diagnosed between 1975 and 2014 from the Surveillance, Epidemiology, and End Results (SEER)-9 cancer registries. Standardized incidence ratios (SIRs) were calculated by calendar year of diagnosis among PCa patients receiving radiotherapy and not. P trends were evaluated using Poisson regression. 10-year cumulative incidence of BC and RC was calculated utilizing competing risk regression model. Result Of PCa patients treated with radiotherapy, SIRs of BC increased from .82 (95% CI: .35- 1.61) in 1980–1984 to 1.58 (95% CI: 1.48–1.68) in 2010-2014 ( Ptrend =.003). SIRs of RC increased from 1.01 (95% CI: .27-2.58) in 1980–1984 to 1.54 (95% CI: 1.31–1.81) in 2010-2014 ( Ptrend =.025). No statistically significant change in both BC and RC incidence was observed. The 10-year cumulative incidence of BC increased from 1975–1984 (.04%) to 2005–2014 (.15%) among PCa treated with radiotherapy. Simultaneously, the 10-year cumulative incidence of RC was demonstrated to range from 1975–1984 (.02%) to 2005–2014 (.11%). Conclusion we have observed an increasing trend in second BC and RC incidence in PCa patients receiving radiotherapy. There was no significant change in the incidence of second BC and RC in PCa without radiotherapy. These results reflect the increasing clinical burden of second malignant tumors in PCa patients undergoing radiotherapy.

EIF4A3 (Eukaryotic translation initiation factor 4A3 (EIF4A3) was recently recognized as an oncogene; however, its role in BLCA (bladder cancer) remains unclear. We explored EIF4A3 expression and its prognostic value in BLCA in public datasets, including the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). Thereafter, the association between EIF4A3 expression and the infiltration of immune cells and immune-checkpoint expression was determined using TIMER2 (Tumor Immune Estimation Resource 2) tool. Additionally, the impact of EIF4A3 on cellular proliferation and apoptosis events in BLCA cell lines was determined by siRNA technology. In this study, EIF4A3 was found to be significantly upregulated in BLCA, upregulated expression of EIF4A3 was related to poor prognosis, advanced histologic grade, subtype, pathological stage, white race, and poor primary therapy outcome. The immune infiltration analysis revealed that EIF4A3 expression was negatively associated with CD8+ and CD4+ T cells and positively with myeloid-derived suppressor cells, macrophage M2, cancer-associated fibroblasts, and Treg cells. Moreover, EIF4A3 was coexpressed with PD-L1 (programmed cell death 1-ligand 1) and its expression was higher in patients responding to anti-PD-L1 therapy. EIF4A3 knockdown significantly inhibited proliferation and promoted apoptosis in 5,637 and T24 cells. In summary, BLCA patients with elevated EIF4A3 expression had an unfavorable prognosis and immunosuppressive microenvironment, and EIF4A3 may facilitate BLCA progression by promoting cell proliferation and inhibiting apoptosis. Furthermore, our study suggests that EIF4A3 is a potential biomarker and therapeutic target for BLCA.

BackgroundMitochondrial metabolic reprogramming (MMR)-mediated immunogenic cell death (ICD) is closely related to the tumor microenvironment (TME). Our purpose was to reveal the TME characteristics of clear cell renal cell carcinoma (ccRCC) by using them.MethodsTarget genes were obtained by intersecting ccRCC differentially expressed genes (DEGs, tumor VS normal) with MMR and ICD-related genes. For the risk model, univariate COX regression and K-M survival analysis were used to identify genes most associated with overall survival (OS). Differences in the TME, function, tumor mutational load (TMB), and microsatellite instability (MSI) between high and low-risk groups were subsequently compared. Using risk scores and clinical variables, a nomogram was constructed. Predictive performance was evaluated by calibration plots and receiver operating characteristics (ROC).ResultsWe screened 140 DEGs, including 12 prognostic genes for the construction of risk models. We found that the immune score, immune cell infiltration abundance, and TMB and MSI scores were higher in the high-risk group. Thus, high-risk populations would benefit more from immunotherapy. We also identified the three genes (CENPA, TIMP1, and MYCN) as potential therapeutic targets, of which MYCN is a novel biomarker. Additionally, the nomogram performed well in both TCGA (1-year AUC=0.862) and E-MTAB-1980 cohorts (1-year AUC=0.909).ConclusionsOur model and nomogram allow accurate prediction of patients’ prognoses and immunotherapy responses.

Abstract Background Penile squamous cell carcinoma (PSCC) survival had no significant improvement since 1990 in the United States. This study aims to get insight into the changing trend and distribution of death causes of PSCC. The epidemiology of PSCC is also investigated. Methods The Surveillance, Epidemiology, and End Results (SEER) (1992–2018) database is utilized to get patients diagnosed with penile squamous cell carcinoma. The trend of incidence, distribution of age, changing trend and distribution of death cause, and survival outcome are analyzed for all PSCC patients and each race. Results Three thousand four hundred and twenty‐three male patients with PSCC are enrolled in our study. The age‐adjusted incidence rate of the white has a slight increase (Annual percent change [APC] = 0.647%). American Indian/Alaska Native men have the highest average annual incidence, while Asian /Pacific Islander men have the lowest. PSCC patients aged 70–80 are the most common, and patients over 80 years have the highest 3‐year (50%) and 5‐year (63.93%) mortality rate. Non‐cancer disease, especially circulatory system disease, is the most common cause of death, whereas the proportion of patients who died of PSCC significantly increased from 21.17% (1992–2001) to 41.3% (2012–2017) in PSCC patients (p

Abstract Objective To investigate the clinical safety and efficacy of a modified early unclamping technique in robot-assisted laparoscopic partial nephrectomy (RAPN). Methods The clinical data of 38 patients with renal tumors who underwent the modified early unclamping technique in RAPN surgery admitted to the Department of Urology, the Third People's Hospital of Hangzhou and the First Affiliated Hospital of Nanchang University from January 2018 to April 2021 were retrospectively analyzed. The control group consisted of 78 patients with renal tumors who underwent standard clamping during the RAPN surgery completed by the same surgeon during the same period. The perioperative-related indicators and postoperative renal function recovery were analyzed and compared between the two groups. Results All patients (n = 116) finished the RAPN successfully, and none were transferred to radical or open surgery in either group. The warm ischemia time in the modified early unclamping group was significantly lower than that in the standard clamping group (P

Abstract Efficient and emergency data dissemination service in vehicular networks (VN) is very important in some situations, such as earthquakes, maritime rescue, and serious traffic accidents. Data loss frequently occurs in the data transition due to the unreliability of the wireless channel and there are no enough available UAVs providing data dissemination service for the large disaster areas. UAV with an adjustable active antenna can be used in light of the situation. However, data dissemination assisted by UAV with the adjustable active antenna needs corresponding effective data dissemination framework. A UAV‐assisted data dissemination method based on network coding is proposed. First, the graph theory to model the state of the data loss of the vehicles is used; the data dissemination problem is transformed as the maximum clique problem of the graph. With the coverage of the directional antenna being limited, a parallel method to find the maximum clique based on the region division is proposed. Lastly, the method's effectiveness is demonstrated by the simulation; the results show that the solution proposed can accelerate the solving process of finding the maximum clique and reduce the number of UAV broadcasts. This manuscript designs a novel scheme for the UAV‐assisted data dissemination in vehicular networks based on network coding. The graph theory is used to model the state of the data loss of the vehicles. With the coverage of the directional antenna being limited, then a parallel method is proposed to find the maximum clique of the graph based on the region division. The effectiveness of the method is demonstrated by the simulation.

BackgroundChemotherapy has been proven to bring survival benefit in patients with resected muscle-invasive bladder cancer (MIBC), which is increasingly recommended. Our objective was to establish an effective model for estimating the overall survival (OS) and cancer-specific survival (CSS) in these patients.Methods2,030 patients diagnosed with resected MIBC receiving chemotherapy were acquired from the Surveillance, Epidemiology, and End Result (SEER) database, which were randomized 7:3 into a primary set (1,421 patients) and an internal validation set (609 patients). Significant predictors for OS and CSS were identified by Cox regression models, which were then utilized to develop prognostic nomogram. The performance of the model was assessed by utilizing calibration, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA).ResultsSix independent prognostic factors, including age, race, histology, T stage, N stage and regional nodes examined, made up the nomogram. The AUCs of the primary cohort was 0.751 and 0.753 for 3- and 5- year OS and 0.751 and 0.754 for 3-and 5- year CSS, respectively. The calibration plots proved the nomograms' satisfactory discrimination. The results of DCA manifested that our models had an excellent clinical applicability. In addition, a risk stratification system was established according to the nomogram' risk score. Obvious difference was found in different groups (P

BackgroundTransforming growth factor (TGF)-β signaling is strongly related to the development and progression of tumor. We aimed to construct a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical prognosis and immunotherapy responses of patients with clear cell renal cell carcinoma (ccRCC).MethodsThe gene expression profiles and corresponding clinical information of ccRCC were collected from the TCGA and the ArrayExpress (E-MTAB-1980) databases. LASSO, univariate and multivariate Cox regression analyses were conducted to construct a prognostic signature in the TCGA cohort. The E-MTAB-1980 cohort were used for validation. Kaplan-Meier (K-M) survival and time-dependent receiver operating characteristic (ROC) were conducted to assess effectiveness and reliability of the signature. The differences in gene enrichments, immune cell infiltration, and expression of immune checkpoints in ccRCC patients showing different risks were investigated.ResultsWe constructed a seven gene (PML, CDKN2B, COL1A2, CHRDL1, HPGD, CGN and TGFBR3) signature, which divided the ccRCC patients into high risk group and low risk group. The K-M analysis indicated that patients in the high risk group had a significantly shorter overall survival (OS) time than that in the low risk group in the TCGA (p < 0.001) and E-MTAB-1980 (p = 0.012). The AUC of the signature reached 0.77 at 1 year, 0.7 at 3 years, and 0.71 at 5 years in the TCGA, respectively, and reached 0.69 at 1 year, 0.72 at 3 years, and 0.75 at 5 years in the E-MTAB-1980, respectively. Further analyses confirmed the risk score as an independent prognostic factor for ccRCC (p < 0.001). The results of ssGSEA that immune cell infiltration degree and the scores of immune-related functions were significantly increased in the high risk group. The CIBERSORT analysis indicated that the abundance of immune cell were significantly different between two risk groups. Furthermore, The risk score was positively related to the expression of PD-1, CTLA4 and LAG3.These results indicated that patients in the high risk group benefit more from immunotherapy.ConclusionWe constructed a novel TGF-β signaling-related genes signature that could serve as an promising independent factor for predicting clinical prognosis and immunotherapy responses in ccRCC patients.