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OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein-protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Bases de Datos Factuales , Análisis Multivariante , Pronóstico , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIaRESUMEN
Lipid metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Lipid accumulation affects cellular energy homeostasis, biofilm synthesis, lipid signal transduction, and phenotypic transformation in ccRCC. Herein, a prognostic-related model was constructed, and the prognostic utility of AUP1, a lipid droplet-regulating very low-density lipoprotein assembly factor, in ccRCC was determined through multiparameter analysis. AUP1 expression was significantly higher in clinical samples than in normal tissues and was closely associated with the clinical stage. The inhibition of AUP1 expression impaired the proliferation, migration, and invasion of ACHN and A498 ccRCC cells in vitro and in vivo. RNA-seq analysis revealed that AUP1 inhibition can significantly reduce the contents of intracellular triglyceride and cholesterol and regulate cell growth by cell cycle arrest, promoting apoptosis and reversing epithelial-mesenchymal transition. AUP1 regulated the synthesis of cholesterol esters and fatty acids (FAs) in ccRCC cells by targeting sterol O-acyltransferase 1 and partially promoted the progression of ccRCC. AUP1 also induced lipid accumulation in ccRCC by promoting the de novo synthesis of FAs (inhibiting protein kinase AMP-activated catalytic subunit alpha 2), inhibiting the rate-limiting enzyme of FA ß oxidation (carnitine palmitoyltransferase 1A), regulating the key enzyme of lipolysis (monoglyceride lipase, MGLL), and inhibiting the lipid transporter StAR-related lipid transfer domain containing 5 (STARD5). However, it did not affect the intracellular cholesterol synthesis pathway. The differential expression and prognostic significance of MGLL and STARD5 in ccRCC should be further studied. AUP1 may serve as a new and effective potential target and prognostic marker for ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Proteínas de la Membrana , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular , Colesterol , Ácidos Grasos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/patología , Metabolismo de los Lípidos , Proteínas de la Membrana/metabolismoRESUMEN
How to make a controller robust and stable to reject the disturbance of uncertainty is an inevitable challenge. Aiming at addressing the lateral control problem for an autonomous road sweeper, a heading-error-based first order linear active disturbance rejective controller (HFO-LADRC) is proposed in this paper. To eliminate the lateral error and the heading error at the same time, a new model, called the heading-error-based model, is proposed for lateral motion, and the Lyapunov function was employed to explore the convergence ability of the heading error and lateral error. Since the heading-error-based model is first order, the ADRC is designed as first order and linear, and each module of the HFO-LADRC has been devised in detail. To ensure solution accuracy, the fourth order Runge-Kutta method was adopted as the differential system solver, and a typical ring scenario and a double lane-changing scenario were designed referencing the standard. Considering the obvious influence, wheelbase uncertainty, steering ratio uncertainty and Gaussian white noise disturbance were taken into account for the tests. The results illustrate that, in the case of both wheelbase uncertainty and steer ratio uncertainty, the HFO-LADRC has strong robustness and stability compared with a typical pure pursuit controller and classical SO-LADRC.
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According to the existing mainstream automatic parking system (APS), a parking path is first planned based on the parking slot detected by the sensors. Subsequently, the path tracking module guides the vehicle to track the planned parking path. However, since the vehicle is non-linear dynamic, path tracking error inevitably occurs, leading to inclination and deviation of the parking. Accordingly, in this paper, a reinforcement learning-based end-to-end parking algorithm is proposed to achieve automatic parking. The vehicle can continuously learn and accumulate experience from numerous parking attempts and then learn the command of the optimal steering wheel angle at different parking slots. Based on this end-to-end parking, errors caused by path tracking can be avoided. Moreover, to ensure that the parking slot can be obtained continuously in the process of learning, a parking slot tracking algorithm is proposed based on the combination of vision and vehicle chassis information. Furthermore, given that the learning network output is hard to converge, and it is easy to fall into local optimum during the parking process, several reinforcement learning training methods in terms of parking conditions are developed. Lastly, by the real vehicle test, it is proved that using the proposed method can achieve a better parking attitude than using the path planning and path tracking-based method.
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Freezing is an effective way of food preservation. However, traditional freezing methods have the disadvantages of low freezing efficiency and generation of large ice crystals, leading to possible damage of food quality. Power ultrasound assisted freezing as a novel technique can effectively reduce the adverse effects during freezing process. This paper gives an overview on recent researches of power ultrasound technique to accelerate the food freezing processes and illustrates the main principles of power ultrasound assisted freezing. The effects of power ultrasound on liquid food, model solid food as well as fruit and vegetables are discussed, respectively, from the aspects of increasing freezing rate and improving microstructure. It is shown that ultrasound assisted freezing can effectively improve the freezing efficiency and promote the formation of small and evenly distributed ice crystals, resulting in better food quality. Different inherent properties of food samples affect the effectiveness of ultrasound application and optimum ultrasound parameters depend on the nature of the samples. The application of ultrasound to the food industry is more likely on certain types of food products and more efforts are still needed to realize the industrial translation of laboratory results.
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Análisis de los Alimentos , Conservación de Alimentos/métodos , Congelación , Calidad de los Alimentos , UltrasonidoRESUMEN
1,2-Bifuctional thiocyanodiphenylphosphinoylation of alkenes is established through the phosphinoyl radical addition followed by Cu-catalyzed thiocyanation. This one-pot reaction is applicable to a range of aromatic, aliphatic, and cyclic alkenes to afford thiocyanodiphenylphosphinoylated compounds in satisfactory yields.
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A new series of mixed valence perovskites, La0.75K0.25AMnTiO6 (A = Sr and Ba) nanocubes, have been synthesized by a mild hydrothermal route. From powder X-ray diffraction (XRD) analysis, the crystal structure of La0.75K0.25AMnTiO6 was solved as the orthorhombic symmetry (space group Pbnm) with a random A-site or B-site arrangement. The phase purity of the products was confirmed by ICP, SEM, and EDS analyses, and the oxidation states of the B-site metal atoms were determined to be +4 for Ti and +3/+4 for Mn from XPS results. The soft ferromagnetic behavior is present in both samples. The Curie point TC has been detected as high as 309 K in La0.75K0.25SrMnTiO6 and 217 K in La0.75K0.25BaMnTiO6. A Griffiths phase can be observed at the high temperature region, which is related to the magnetic inhomogeneity induced by the existence of short-range ferromagnetic clusters. The resistivity measurements indicate that the semiconducting properties of the samples can be depicted better by variable range hopping (VRH) due to a diluted double-exchange interaction of Mn3+-O-Mn4+ with Ti4+ doping.
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Rare earth nanomaterials, which feature long-lived intermediate energy levels and intraconfigurational 4f-4f transitions, are promising supporters for photon upconversion. Owing to their unique optical properties, rare earth upconversion nanomaterials have found applications in bioimaging, theranostics, photovoltaic devices, and photochemical reactions. Here, we review recent advances in the photon upconversion processes of these nanomaterials. We start by considering energy transfer models involved in the study of upconversion emissions, as well as well-established synthesis strategies to control the size and shape of rare earth upconversion nanomaterials. Progress in engineering energy transfer pathways, which play a dominant role in determining upconversion emission outputs, is then discussed. Lastly, representative optical applications of these materials are considered. The aim of this review is to provide inspiration for researchers to explore novel upconversion nanomaterials and extended optical applications.
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Air oxidative radical oxysulfurization of alkynes initiated by 0.5 mol % tert-butyl hydroperoxide with arylthiols is described. The reaction proceeded at room temperature in the presence of 5% mol water to afford selective α-thioaldehydes.
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Herein we report a new way to identify chemical elicitors that induce resistance in rice to herbivores. Using this method, by quantifying the induction of chemicals for GUS activity in a specific screening system that we established previously, 5 candidate elicitors were selected from the 29 designed and synthesized phenoxyalkanoic acid derivatives. Bioassays confirmed that these candidate elicitors could induce plant defense and then repel feeding of white-backed planthopper Sogatella furcifera.
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Resistencia a la Enfermedad , Hemípteros , Oryza , Fenoxiacetatos , Plantas Modificadas Genéticamente , Animales , Femenino , Fenoxiacetatos/química , Fenoxiacetatos/farmacología , Plantas Modificadas Genéticamente/genéticaRESUMEN
Soft pneumatic actuators (SPAs) are commonly used in various applications because of their structural compliance, low cost, ease of manufacture, high adaptability, and safe human-robot interaction. The traditional approach for achieving proportional control of soft pneumatic robots requires the use of industrial proportional valves or syringe drivers, which are not only rigid and bulky but also hard to be integrated into the body of soft robots. In our previous research, we developed a Magnetorheological elastomer (MRE)-based soft valve that showed advantages for controlling SPAs due to its compliance, compactness, robustness, and compatibility for continuous pressure modulation. Modern soft robots with multiple chambers require more MRE valves onboard for their control. However, merely packing more MRE valves for soft robots can cause problems like magnetic interference, flow rate deviation, and overheating. Therefore, in this study, we proposed a two-dimensional MRE valve array design to solve issues of magnetic interference and overheating when expanding from a single MRE proportional valve into an integrated array. The magnetic interference and the overheating problem were investigated through multiphysics simulation, bringing the optimal choice of valve spacing (1.2 times the single valve diameter), magnetic coil pole arrangement (same pole), and the cooling system design (internal cooling chamber with flowing water). Physical experiments showed that our MRE valve array maintained its original flowrate performance with low magnetic interference (0.89 mT) and low coil temperature (under 73.9°C for 5 min).
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Mulching practices have been used to improve peach growth and production across the globe. However, the impact of mulching on the physiochemical properties and soil characteristics of orchards remains largely unknown. This study aimed to decipher the impacts of various mulching patterns on the soil environment and the quality of Prunus persica fruit in "Zijinhuangcui". Three treatments were set up, which included black ground fabric mulch (BF) and two living grass mulch treatments (HV: hairy vetch and RG: ryegrass). The results showed that different mulching treatments have different effects on soil, plant growth, and fruit quality. Living grass mulch treatments, especially the HV treatment, significantly improved soil nutrients by enhancing nitrogen-related indicators. Of note, the BF treatment had higher total phosphorus and available phosphorus contents than the HV and RG treatments. The HV treatment had the highest relative abundance of Proteobacteria (33.49%), which is associated with symbiotic nitrogen fixation, followed by RG (25.62%), and BF (22.38%) at the young fruit stage. Similarly, the abundance of Terrimonas, which has a unique nitrogen fixation system at the genus level, was significantly higher in the living grass mulch (HV, 1.30-3.13% and RG, 2.27-4.24%) than in the BF treatment. Living grass mulch also promoted tree growth, increased fruit sugar content, sugar-related components, and sugar-acid ratio, and reduced the acid content. Collectively, the findings of this study show that living grass mulch can promote tree growth and improve fruit quality by improving soil fertility, bacterial diversity, and richness.
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Background: Kidney renal clear cell carcinoma (KIRC) originates from proximal tubular cells and is the most common subtype of renal cell carcinoma. KIRC is characterized by changes in lipid metabolism, and obesity is a risk factor for it. C1q And TNF Related 1 (C1QTNF1), a novel adipokine and member of the C1q and TNF-related protein (CTRP) family, has been shown to affect the progression of various cancers. However, the role of C1QTNF1 in KIRC has not been studied. Methods: The Wilcoxon rank sum test was used to analyze the expression of C1QTNF1 in KIRC tissues and normal tissues. The relationship between clinicopathological features and C1QTNF1 levels was also examined by logistic regression and the Wilcoxon rank sum test. In addition, the effect of C1QTNF1 on the prognosis of KIRC patients was analyzed by Kaplan-Meier (KM). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the potential signaling pathways and biological functions of differential genes. A nomogram was constructed to predict the prognosis of KIRC patients. Spearman correlation analysis was performed to determine the association between C1QTNF1 expression and immune cell infiltration and immune checkpoint genes. The upstream miRNAs and lncRNAs of C1QTNF1 were predicted by the ENCORI online tool. Finally, we examined the proliferation, invasion, and migration abilities of KIRC cells after C1QTNF1 knockdown. Results: The expression of C1QTNF1 in KIRC tissues was significantly higher than in normal renal tissues. Patients with higher C1QTNF1 expression had a poor prognosis, a finding supported by Kaplan-Meier survival analysis. C1QTNF1 expression was significantly correlated with TNM and pathologic stages, age, and gender (p < 0.05). The C1QTNF1 expression level was significantly correlated with immune cell infiltration and immune checkpoint genes in KIRC. Additionally, high C1QTNF1 expression was associated with poor prognosis in stage I and II, T1 and T2, T3 and T4, N0, and M0 patients (HR > 1, p < 0.05). The calibration diagram shows that the C1QTNF1 model has effective predictive performance for the survival of KIRC patients. Knockdown of C1QTNF1 inhibited KIRC cell proliferation, cell migration, and cell invasion. In addition, CYTOR and AC040970.1/hsa-miR-27b-3p axis were identified as the most likely upstream ncRNA-related pathways of C1QTNF1 in KIRC. Conclusion: In conclusion, our study suggests that high expression of C1QTNF1 is associated with KIRC progression and immune infiltration. The increased expression of C1QTNF1 suggests a poor prognosis in KIRC patients.
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BACKGROUND: The ability to translate concrete manipulatives into abstract mathematical formulas can aid in the solving of mathematical word problems among students, and metacognitive prompts play a significant role in enhancing this process. AIMS: Based on the concept of semantic congruence, we explored the effects of metacognitive prompts and numerical ordinality on information searching and cognitive processing, throughout the process of solving mathematical word problems among primary school students in China. SAMPLE: Participants included 73 primary school students (38 boys and 35 girls) with normal or corrected visual acuity. METHODS: This study was based on a 2 (prompt information: no-prompt, metacognitive-prompt) × 2 (number attribute: cardinal number, ordinal number) mixed experimental design. We analysed multiple eye-movement indices, such as fixation duration, saccadic amplitude, and pupil size, since they pertained to the areas of interest. RESULTS: When solving both types of problems, pupil sizes were significantly smaller under the metacognitive-prompt condition compared with the no-prompt condition, and shorter dwell time for specific sentences, conditional on metacognitive prompts, indicated the optimization of the presented algorithm. Additionally, the levels of fixation durations and saccadic amplitudes were significantly higher when solving ordinal number word problems compared with solving ordinal number problems, indicating that primary school students were less efficient in reading and faced increased levels of difficulty when solving ordinal number problems. CONCLUSIONS: The results indicate that for Chinese upper-grade primary school students, cognitive load was lower in the metacognitive prompting condition and when solving cardinal problems, and higher when solving ordinal problems.
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Cognición , Metacognición , Masculino , Femenino , Humanos , Tecnología de Seguimiento Ocular , Solución de Problemas , LenguajeRESUMEN
In recent years, more attention has been paid to expanding the abundance of Circular RNAs (circRNAs), while the circRNAs that have been found to have significant functions have not been studied in different diseases. CircFNDC3B is one of the most researched circRNAs generated from fibronectin type III domain-containing protein 3B (FNDC3B) gene. Accumulating researches have reported the multiple functions of circFNDC3B in different cancer types and other non-neoplastic diseases, and predicted that circFNDC3B might be a potential biomarker. Notably, circFNDC3B can play roles in different diseases by binding to various microRNAs (miRNAs), binding to RNA-binding proteins (RBPs), or encoding functional peptides. This paper systematically summarizes the biogenesis and function of circRNAs, reviews and discusses the roles and molecular mechanisms of circFNDC3B and its target genes in different cancers and non-neoplastic diseases, which will do favor to broaden our comprehension of the function of circRNAs and facilitate subsequent research on circFNDC3B.
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This meta-analysis investigated the efficacy and adverse drug reactions (ADRs) of three different adrenergic alpha-antagonists during the treatment of pediatric ureteral stones. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry until January 2022. We identified 7 articles, including six RCTs and one cohort study. 610 children received either adrenergic alpha-antagonists or placebo. The results confirmed that the three different adrenergic alpha-antagonists could significantly increase the ureteral calculi expulsive rate and shorten the ureteral calculi expulsive time, regardless of the size of the stone "<5â mm" or "5-10â mm". Subgroup analysis suggested that all three adrenergic alpha-antagonists increased the ureteral calculi expulsive rate. Tamsulosin and silodosin also have the effect of shortening ureteral calculi expulsive time, while doxazosin has an insignificant effect on ureteral calculi expulsive time. Besides, tamsulosin and silodosin obviously reduced the number of pain episodes caused by ureteral calculi in children. We analyzed the treatment-emergent adverse events (TEAEs) caused by the treatment of three different adrenergic alpha-antagonists to explore their ADRs. The probability of ADRs was increased after treatment with adrenergic alpha-antagonists. Further subgroup analysis revealed the application of tamsulosin was positively correlated with ADRs in children with ureteral calculi, while the application of doxazosin and silodosin had no statistically significant effect on the probability of TEAEs. In a conclusion, this article systematically analyzed the efficacy and ADRs of three different adrenergic alpha-antagonists, and provided reference and guidance for the application of adrenergic alpha-antagonists to treat children ureteral calculi.
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Background CXCLs are a group of low-molecular-weight growth factors secreted by cells, mainly through G protein-coupled receptors for signal transduction and induction of cell chemotactic motility. Their abnormal expression is linked to immune cell activity in cancer and tumor growth and progression. However, the differential expressions of CXCLs in ccRCC, prognostic prospects, and immune infiltration have not been clearly explored. Objective This study aimed to analyze the expression profile of CXCL family members in clear cell renal cell carcinoma, its prognostic significance, and the correlation between CXCL family members and tumor immunity. Methods The expression difference of CXCLs between ccRCC and normal renal tissues was analyzed by the TCGA database. The prognostic value of CXCLs in ccRCC was analyzed by the Kaplan-Meier Plotter. The copy number variation (CNV) of CXCLs in ccRCC was explored through the GSCA website. The cBioPortal online tool was used to screen out 355 co-expressed genes significantly related to CXCLs. The protein-protein interaction network of co-expressed genes was constructed using the STRING database, and the pathways that significantly enriched these genes were explored using Metascape. We then used the least absolute shrinkage and selection operator (LASSO) regression analysis to develop a predictive risk model for ccRCC patients. The relationship between CXCLs and tumor immune cell infiltration was analyzed. Finally, drugs interacting with CXCLs were analyzed using the DGIdb database. Results It was observed that mRNA expression levels of CXCL-2,-3,-4,-5,-9,-10,-11,-13, and -16 in the tissue of KIRC were higher than normal KIRC tissue. In contrast, CXCL12 expression decreased. Furthermore, CXCL5,-9,-10,-11,-12, and -13 mRNA expression was significantly correlated with the clinical stage. In KIRC patients, elevated CXCL1,-2,-5, and -13 expression was associated with shorter overall survival, while elevated CXCL14 expression was associated with a better prognosis. Through LASSO regression analysis, we obtained a 5-gene prognostic signature. This prognostic feature is associated with the infiltration of multiple immune cells. Conclusion In this study, we evaluated the expression levels of CXCL genes in KIRC and their prognostic potential in KIRC. CXCL-5,-9,-10,-11,-12, and -13 may be associated with ccRCC progression, and CXCL-1,-2,-5,-13, and -14 may be potential prognostic markers.
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A hard issue in the field of microrobots is path planning in complicated situations with dense obstacle distribution. Although the Dynamic Window Approach (DWA) is a good obstacle avoidance planning algorithm, it struggles to adapt to complex situations and has a low success rate when planning in densely populated obstacle locations. This paper suggests a multi-module enhanced DWA (MEDWA) obstacle avoidance planning algorithm to address the aforementioned issues. An obstacle-dense area judgment approach is initially presented by combining Mahalanobis distance, Frobenius norm, and covariance matrix on the basis of a multi-obstacle coverage model. Second, MEDWA is a hybrid of enhanced DWA (EDWA) algorithms in non-dense areas with a class of two-dimensional analytic vector field methods developed in dense areas. The vector field methods are used instead of the DWA algorithms with poor planning performance in dense areas, which greatly improves the passing ability of microrobots over dense obstacles. The core of EDWA is to extend the new navigation function by modifying the original evaluation function and dynamically adjusting the weights of the trajectory evaluation function in different modules using the improved immune algorithm (IIA), thus improving the adaptability of the algorithm to different scenarios and achieving trajectory optimization. Finally, two scenarios with different obstacle-dense area locations were constructed to test the proposed method 1000 times, and the performance of the algorithm was verified in terms of step number, trajectory length, heading angle deviation, and path deviation. The findings indicate that the method has a smaller planning deviation and that the length of the trajectory and the number of steps can both be reduced by about 15%. This improves the ability of the microrobot to pass through obstacle-dense areas while successfully preventing the phenomenon of microrobots going around or even colliding with obstacles outside of dense areas.
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Purpose: The mitogen-activated protein kinase (MAPK) signaling pathway is often studied in oncology as the most easily mentioned signaling pathway. This study aims to establish a new prognostic risk model of MAPK pathway related molecules in kidney renal clear cell carcinoma (KIRC) based on genome and transcriptome analysis. Methods: In our study, RNA-seq data were acquired from the KIRC dataset of The Cancer Genome Atlas (TCGA) database. MAPK signaling pathway-related genes were obtained from the gene enrichment analysis (GSEA) database. We used "glmnet" and the "survival" extension package for LASSO (Least absolute shrinkage and selection operator) regression curve analysis and constructed a prognosis-related risk model. The survival curve and the COX regression analysis were used the "survival" expansion packages. The ROC curve was plotted using the "survival ROC" extension package. We then used the "rms" expansion package to construct a nomogram plot. We performed a pan-cancer analysis of CNV (copy number variation), SNV (single nucleotide variant), drug sensitivity, immune infiltration, and overall survival (OS) of 14 MAPK signaling pathway-related genes using several analysis websites, such as GEPIA website and TIMER database. Besides, the immunohistochemistry and pathway enrichment analysis used The Human Protein Atlas (THPA) database and the GSEA method. Finally, the mRNA expression of risk model genes in clinical renal cancer tissues versus adjacent normal tissues was further verified by real-time quantitative reverse transcription (qRT-PCR). Results: We performed Lasso regression analysis using 14 genes and created a new KIRC prognosis-related risk model. High-risk scores suggested that KIRC patients with lower-risk scores had a significantly worse prognosis. Based on the multivariate Cox analysis, we found that the risk score of this model could serve as an independent risk factor for KIRC patients. In addition, we used the THPA database to verify the differential expression of proteins between normal kidney tissues and KIRC tumor tissues. Finally, the results of qRT-PCR experiments suggested large differences in the mRNA expression of risk model genes. Conclusions: This study constructs a KIRC prognosis prediction model involving 14 MAPK signaling pathway-related genes, which is essential for exploring potential biomarkers for KIRC diagnosis.
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PURPOSE: To detect the expression of sphingosine kinase 1 (SPHK1) in clear cell renal cell carcinoma (ccRCC) and explore its biological role in the occurrence and development of ccRCC through regulation of fatty acid metabolism. METHODS: Using the Cancer Genome Atlas database, SPHK1 expression and its clinical significance were detected in clear cell renal cell carcinoma. Immunohistochemistry was performed to detect SPHK1 expression in RCC samples in our hospital. The connection between the SPHK1 levels and clinicopathological features of patients was assessed. Nile Red was used to detect fatty acids in cells. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to determine the effect of SPHK1 on renal cell viability and proliferation, respectively. Additionally, the effects of SPHK1 on the proliferation and metastasis of ccRCC were studied using wound healing and Transwell assays. Fatty acids were added exogenously in recovery experiments and western blotting was performed to determine the effect of SPHK1 on fatty acid metabolism in ccRCC. Finally, the effects of SPHK1 on tumor growth were investigated in a xenograft model. RESULTS: Bioinformatics analysis revealed that SPHK1 expression was upregulated in kidney RCC. OverSPHK1 expression was associated with poor prognosis for ccRCC patients. High SPHK1 expression was detected in human ccRCC. SPHK1 expression was related to clinicopathological features, such as tumor size and Furman grade. Additionally, cell proliferation, migration, and invasion were inhibited in ccRCC cells with low SPHK1 expression. In rescue experiments, proliferation, migration, and invasion were restored. In vivo, reduced SPHK1 levels correlated with lower expression of fatty acid synthase, stearoyl-CoA desaturase 1, and acetyl CoA carboxylase, and slowed tumor growth. CONCLUSIONS: SPHK1 is abnormally overexpressed in human ccRCC. Patients with ccRCC may benefit from treatments that target SPHK1, which may also serve as a prognostic indicator.