RESUMEN
OBJECTIVE: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa). METHODS: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis. RESULTS: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified. CONCLUSIONS: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa.
Asunto(s)
Neoplasias de la Próstata , Macrófagos Asociados a Tumores , Masculino , Humanos , Pronóstico , Neoplasias de la Próstata/metabolismo , Macrófagos , Fenotipo , Microambiente TumoralRESUMEN
π-Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main-group electron-donating carbazolyl moieties or the π-expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure-of-eight topology as a result of the conjugation patterns of 2,2',7,7'-spirobifluorenyl in 1 and triarylamine-coupled aza[7]helicene-based building blocks in 2. This electronic nature of redox-active, carbazole-rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open-shell cyclophanes. Their redox-dependent electronic states of the resulting multispin polyradicals have been characterized by VT-ESR, UV/Vis-NIR absorption and spectroelectrochemical measurements. The singlet (ΔES-T=-1.29â kcal mol-1) and a nearly degenerate singlet-triplet ground state (ΔES-T(calcd)=-0.15â kcal mol-1 and ΔES-T(exp)=0.01â kcal mol-1) were proved for diradical dications 12+2â and 22+2â , respectively. Our work provides an experimental proof for the construction of electron-donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors.
RESUMEN
PURPOSE: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. METHODS: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. RESULTS: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.
Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Radioisótopos de Galio , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Terapia Neoadyuvante , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
Nanozymes have been relatively well explored, and bimetal-doped nanozymes have attracted much exploration due to their superior catalytic activity. We developed bimetallic FeCu/NPCs and Cu/NPCs nanozymes, which have good catalytic properties due to the coordination of Fe and Cu with N and P. The nanozymes acted as sensing elements in a cascade reaction system to effectively recognize seven terpenoids, including menthol (Men), paeoniflorin (Pae), camphor (Cam), paclitaxel (Pac), andrographolide (Andro), ginkgolide A (Gin A), and piperone (Pip). Terpenoids act as inhibitors of acetylcholinesterase (AChE) and reduce the hydrolysis of acetylcholine (ATCh), providing insight into establishing a simple and distinct assay for terpenoids. Notably, the sensor array distinguished seven terpenoids with concentrations as low as 10 ng/mL and achieved high-precision detection of mixed samples with different molar ratios and 21 unknown samples. Finally, the sensor array successfully distinguished and identified multiple terpenoids in herbal samples.
Asunto(s)
Acetilcolinesterasa , Terpenos , Humanos , Colorimetría , AcetilcolinaRESUMEN
OBJECTIVE: To identify CD8+ T cell-related molecular clusters and establish a novel gene signature for predicting the prognosis and efficacy of immunotherapy in bladder cancer (BCa). METHODS: Transcriptome and clinical data of BCa samples were obtained from the Cancer Genome Atlas (TCGA) and GEO databases. The CD8+ T cell-related genes were screened through the CIBERSORT algorithm and correlation analysis. Consensus clustering analysis was utilized to identified CD8+ T cell-related molecular clusters. A novel CD8+ T cell-related prognostic model was developed using univariate Cox regression analysis and Lasso regression analysis. Internal and external validations were performed and the validity of the model was validated in a real-world cohort. Finally, preliminary experimental verifications were carried out to verify the biological functions of SH2D2A in bladder cancer. RESULTS: A total of 52 CD8+ T cell-related prognostic genes were screened and two molecular clusters with notably diverse immune cell infiltration, prognosis and clinical features were developed. Then, a novel CD8+ T cell-related prognostic model was constructed. The patients with high-risk scores exhibited a significantly worse overall survival in training, test, whole TCGA and validating cohort. The AUC was 0.766, 0.725, 0.739 and 0.658 in the four cohorts sequentially. Subgroup analysis suggested that the novel prognostic model has a robust clinical application for selecting high-risk patients. Finally, we confirmed that patients in the low-risk group might benefit more from immunotherapy or chemotherapy, and validated the prognostic model in a real-world immunotherapy cohort. Preliminary experiment showed that SH2D2A was capable of attenuating proliferation, migration and invasion of BCa cells. CONCLUSIONS: CD8+ T cell-related molecular clusters were successfully identified. Besides, a novel CD8+ T cell-related prognostic model with an excellent predictive performance in predicting survival rates and immunotherapy efficacy of BCa was developed.
Asunto(s)
Inmunoterapia , Neoplasias de la Vejiga Urinaria , Humanos , Linfocitos T CD8-positivos , Pronóstico , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.
Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Investigadores , Análisis por Conglomerados , Bases de Datos Factuales , PacientesRESUMEN
Nanozymes have both the high catalytic activity of natural enzymes and the stability and economy of mimetic enzymes. Research on nanozymes is rapidly emerging, and the continuous development of highly catalytic active nanozymes is of far-reaching significance. This work reports heteroatomic nitrogen (N) and phosphorus (P) double-doped mesoporous carbon structures and metallic Fe coordination generated sponge-like nanozymes (Fe/NPCs) with good peroxidase activity. On this basis, we constructed a highly sensitive colorimetric sensor with cysteine and phenol as simulated analytes using Fe/NPCs nanozymes, and the response limits reached 53.6 nM and 5.4 nM, respectively. Besides, the method has high accuracy in the detection of cysteine and phenol at low concentrations in serum and tap water, which lays a foundation for application in the fields of environmental protection and biosensors.
Asunto(s)
Colorimetría , Fenol , Catálisis , Cisteína , Peróxido de Hidrógeno/química , Peroxidasas/química , FenolesRESUMEN
Concerns are growing over time on the adverse health effects of air pollution. However, the association between ambient air pollution and blood sex hormones in men is poorly understood. We included 72,917 men aged 20-55 years from February 2014 to December 2019 in Beijing, China in this study. Blood testosterone, follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin levels of each participant were measured. We collected exposure data of daily ambient levels of particulate matter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), nitrogen dioxide, sulfur dioxide (SO2), carbon monoxide, and ozone. Generalized linear mixed models were used to analyze the potential association between ambient air pollution exposure and blood sex hormone levels. The results showed that both immediate and short-term cumulative PM2.5, PM10, and SO2 exposure was related to altered serum sex hormone levels in men, especially testosterone. An increase of 10 µg/m3 in PM2.5 and PM10 in the current day was related to a 1.6% (95% confidence interval [CI]: 0.9%-2.3%) and 1.1% (95% CI: 0.5%-1.6%) decrease in testosterone, respectively, and a decreasing tendency of accumulated effects persisted within lag 0-30 days. The present study demonstrated that it is important to control ambient air pollution exposure to reduce effects on the reproductive health of men.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China , Exposición a Riesgos Ambientales/análisis , Humanos , Masculino , Dióxido de Nitrógeno/análisis , Ozono/análisis , Material Particulado/análisis , Dióxido de Azufre/análisis , TestosteronaRESUMEN
A sustainable and transition metal-free approach for C3 chalcogenation and chalcogenocyanation of imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was performed in the presence of catalytic iodine in aqueous medium, which afforded either chalcogenated or chalcogenocyanated imidazopyridines under temperature control. The current protocol featured a broad substrate scope, transition metal-free and organic solvent-free conditions, operational convenience, and gram-scale production.
RESUMEN
An efficient Cu-catalyzed direct sulfonylation of indolines with easily accessible sulfonyl chlorides has been realized under an air atmosphere via a chelation-assisted strategy. This protocol exhibits several unique characteristics, including broad substrate scope, good functional group tolerance, and operational convenience, which enable a regioselective access to a variety of C-7 functionalized indoline scaffolds in moderate to good yields. The mechanistic study reveals that the sulfonyl radical might be involved in this transformation.
RESUMEN
RATIONALE: Maleic acid is an industrial-grade chemical that is often used in adhesives, stabilizers, and preservatives. It is unknown whether long-term consumption of maleic acid modified starch is harmful to humans. However, many studies have indicated that maleic acid causes renal tubular damage in animal models, even as the associated pathways remain unclear. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) is the most innovative of the label-free quantitative technologies which have better quantification performance. Therefore, SWATH technology was used to investigate the effect of maleic acid on the rat kidney proteome in this study. METHODS: Sprague-Dawley(SD) rats were treated with 0 mg/kg (control), 6 mg/kg (low-dose), 10 mg/kg (medium-dose), and 60 mg/kg (high-dose) of maleic acid. After kidney protein extraction, 28% SDS-PAGE was used, followed by in-gel digestion and desalting. Next, the samples were analyzed with ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS), and data-dependent acquisition (DDA) and SWATH technology were also used. The gene ontology and pathway analysis were accomplished. Ultimately, these protein biomarkers were validated by using scheduled high-resolution multiple reaction monitoring (sMRMHR ). RESULTS: Comparisons of the control group with the other three groups revealed that 95, 130, and 103 proteins were expressed at significantly different levels in the control group and in the low-dose, medium-dose, and high-dose groups, respectively. According to the gene ontology analysis, the major processes that these proteins were involved in were metabolic processes, biological regulation, cellular processes, and responses to stimuli; the major functions that these proteins were involved in were binding, hydrolase activity, catalytic activity, and oxidoreductase activity; and the major cellular components hat they were involved in were the cytoplasm, extracellular region, membrane, and mitochondria. According to the KEGG pathway analysis, these proteins were involved in 35 pathways, five of which, the carbohydrate metabolism, folate biosynthesis, renal tubular resorption, amino acid metabolism, and Ras signaling pathways, are discussed in this study. Ultimately, 19 proteins involved in 12 important pathways were validated by sMRMHR . CONCLUSIONS: It was demonstrated that maleic acid caused insufficient energy production, which might lead to a decrease in the activity of the sodium-potassium ATP pump and hydrogen ion ATP pump, which could in turn have caused renal tubular resorption and hydrogen ion regulation to be blocked, thus leading to the accumulation of hydrogen ions in the renal tubules, which would then result in renal tubular acidification followed finally by Fanconi syndrome.
Asunto(s)
Riñón/efectos de los fármacos , Maleatos/farmacología , Proteoma/metabolismo , Animales , Riñón/química , Riñón/metabolismo , Maleatos/efectos adversos , Espectrometría de Masas/métodos , Proteoma/análisis , Proteómica/métodos , Ratas Sprague-DawleyRESUMEN
Introduction: In the face of an increasingly challenging and rapidly evolving business environment, not all the employees exhibit the requisite resilience necessary to recover from adversity. From both the individual and organizational perspectives, enhancing employee resilience emerges as a critical issue not only in the practical and academic fields. In the Chinese culture, this research aims to investigate how and why collectivism-oriented human resource management (C-HRM) fosters employee resilience. Drawing on the group engagement model, we propose a serial mediating effect of perceived overall fairness and three dimensions of social identity between C-HRM and employee resilience. Methods: Using a sample of frontline employees in the hospitality industry, we conducted a field survey among 342 employees (study 1) and a two-wave online survey among 294 hospitality employees (study 2). Results: Findings from empirical analysis indicated that C-HRM significantly increases overall fairness perception of hospitality frontline employees and in turn, their identification and respect, which further fertilize employee resilience. In addition, the indirect effect of C-HRM on employee resilience through perceived overall fairness and pride was not statistically significant. Discussion: These important findings are expected to help employees cope with the workplace pressures caused by ongoing challenges and change, and contribute to sustainable career development.
RESUMEN
OBJECTIVES: In this real-world approach, we examined the serum Anti-Mullerian Hormone (AMH) level and the relationship with serum IgG subclass in the infertile women. METHODS: A total of 574 female participants were recruited for this study. The serum AMH, IgG subclass(IgG1, IgG2, IgG3, IgG4) and immunoglobulin (Ig) GãIgMãIgAãIgE as well as complement C3, C4 were analyzed. The difference in serum AMH level was assessed according categorized as above or below the median of the ratio of serum IgG subclass(IgG1, IgG2, IgG3, IgG4) to total IgG (RIgG subclass/IgG). RESULTS: The serum AMH level of the low RIgG1/IgG group is significantly decreased than that high RIgG1/IgG group (p < 0.05). The Spearman correlation analysis showed that the serum AMH level was significantly negatively correlated with age and significantly positively correlated with serum IgG1 levels respectively (p < 0.05). GLMMs multivariate model showed that after adjusting the covariate and possible mixed factors including age, serum immunoglobulin, complement C3 and C4, the serum AMH level was significantly positively correlated with IgG1 level (p < 0.01). CONCLUSIONS: Decreased serum IgG1 may significantly affect the ovarian reserve function of women. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.
Asunto(s)
Hormona Antimülleriana , Infertilidad Femenina , Femenino , Humanos , Inmunoglobulina G , Estudios Retrospectivos , SueroRESUMEN
KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S2MMAM). S2MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2MF-CN). S2MMAM facilitates the execution of the classification task by transferring the useful information captured in SMF-SN to the S2MF-CN to improve the model prediction accuracy. In SMF-SN, we propose a Triple Attention-guided Feature Aggregation module for obtaining segmentation features that incorporate high-level semantic abstract features and low-level semantic detail features. Segmentation features provide pre-guidance and key information expansion for S2MF-CN. S2MF-CN shares the encoder and decoder parameters of SMF-SN, which enables S2MF-CN to obtain rich classification features. S2MF-CN uses the proposed Intra and Inter Mutual Guidance Attention Fusion (I2MGAF) module to first guide segmentation and classification feature fusion to extract hidden multi-scale contextual information. I2MGAF then guides the multidimensional fusion of genetic data and CT image data to compensate for the lack of information in single modality data. S2MMAM achieved 83.27% AUC and 81.67% accuracy in predicting KRAS gene mutation status in NSCLC. This method uses medical image CT and genetic data to effectively improve the accuracy of predicting KRAS gene mutation status in NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Biopsia , Mutación , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Although many excellent nanozymes have been developed, designing and synthesizing highly active nanozymes is still challenging. Here, we developed a metal-based nanozyme (metal = Co, Fe, Cu, Zn) with a three-dimensional network structure. It possesses excellent peroxidase activity and catalyzes the reaction between H2O2 and TMB to produce blue oxTMB, while antioxidants have different reducing power on the oxidation product of TMB (oxTMB), which leads to different absorbance and color changes. Using these color reactions, different nanozymes were used to form a colorimetric sensor array with seven antioxidants, and seven antioxidants were sensitively identified. And the differences between the three nanozymes were compared by density functional theory calculations and enzyme kinetic curve results. In conclusion, the colorimetric sensor array based on metal-based nanozymes provides a good strategy for the identification and detection of antioxidants, which has a broad application prospect.
Asunto(s)
Antioxidantes , Colorimetría , Peróxido de Hidrógeno , Metales , FísicaRESUMEN
Background: Many imaging scoring models have been developed for tumor surgery to provide critical guidance for the selection of surgical methods. However, little research has been aimed at developing scoring models for adrenal tumors and retroperitoneal laparoscopic adrenal surgery (RLAS), which has become the primary technique for treating adrenal tumors. The study set out to establish a computed tomography (CT)-based adrenal tumor scoring model for predicting perioperative outcomes in patients with adrenal tumors who have undergone RLAS. Methods: The retrospective analysis included 306 patients with adrenal tumors diagnosed by preoperative unenhanced or enhanced CT from January 2014 to August 2018 in the First Affiliated Hospital of Fujian Medical University. CT images were used to quantify the tumor location and size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the adhesion of periadrenal fat (PF); and the tumor CT enhancement value. We conducted multivariate ordinal logistic regression analysis to screen variables and performed principal component analysis to construct a novel scoring model for RLAS. The perioperative outcomes of RLAS were evaluated according to postoperative length of stay, operative time (OT), intraoperative blood loss (IBL), and postoperative complications. Results: The final scoring model included tumor size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the tumor CT enhancement value; the adhesion of the PF; and the functional status of adrenal tumors. The total score had positive correlations with the OT (rs=0.431), IBL (rs=0.446), and postoperative length (rs=0.180) (all P values <0.001). Compared to any single metric, the total score provided better prediction of OT and IBL. The grading system for RLAS based on the scoring model also performed well in predicting the complexity and difficulty of RLAS. The coincidence rate for these factors was good (all P values <0.001). Conclusions: The developed model is feasible and repeatable in the prediction of the perioperative outcomes, complexity, and difficulty of RLAS.
RESUMEN
PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.
Asunto(s)
Imagen por Resonancia Magnética , Terapia Neoadyuvante , Nomogramas , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Resultado del Tratamiento , Curva ROC , RadiómicaRESUMEN
Aberrant activation of the epithelial-mesenchymal transition (EMT) pathway drives the development of solid tumors, which is precisely regulated by core EMT-related transcription factors, including Twist1. However, the expression pattern and regulatory mechanism of Twist1 in the progression of bladder cancer is still unclear. In this study, we explore the role of Twist1 in the progression of bladder cancer. We discovered that the EMT regulon Twist1 protein, but not Twist1 mRNA, is overexpressed in bladder cancer samples using RT-qPCR, western blot and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation (Co-IP) coupled with liquid chromatography and tandem mass spectrometry identified USP5 as a binding partner of Twist1, and the binding of Twist1 to ubiquitin-specific protease 5 (USP5) stabilizes Twist through its deubiquitinase activity to activate the EMT. Further studies found that USP5 depletion reduces cell proliferation, invasion and the EMT in bladder cancer cells, and ectopic expression of Twist1 rescues the adverse effects of USP5 loss on cell invasion and the EMT. A xenograft tumor model was used to reconfirmed the inhibitor effect of silencing USP5 expression on tumorigenesis in vivo. In addition, USP5 protein levels are significantly elevated and positively associated with Twist1 levels in clinical bladder cancer samples. Collectively, our study revealed that USP5-Twist1 axis is a novel regulatory mechanism driving bladder cancer progression and that approaches targeting USP5 may become a promising cancer treatment strategy.
Asunto(s)
Proteína 1 Relacionada con Twist , Neoplasias de la Vejiga Urinaria , Humanos , Animales , Proteína 1 Relacionada con Twist/genética , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria , Transformación Celular Neoplásica , Modelos Animales de Enfermedad , Proteasas Ubiquitina-EspecíficasRESUMEN
Underground mine fires are a threat to the safety and health of mine workers. The timely determination of the location and size of an underground fire is of great importance in developing firefighting strategies and reducing the risk of any injuries. Machine learning was used in this paper to develop a predictive model for fire location and fire size in an underground mine. The ventilation data were obtained by simulating different mine fire scenarios with MFire. The ventilation data of all airways were used as features to predict the fire location. Based on the feature importance, five airways were selected to monitor, and the airflow data of the selected airways were used to predict the fire location and fire size. An accuracy score of 0.920 was obtained for the prediction of fire location. In addition, in-depth analyses were conducted to characterize the wrong predictions with the purpose of improving the performance of the random forest model. The results show that the occurrence of fire at closely connected airways at some locations can generate misleading ventilation data for each other and the model performance can be further improved to 0.962 by grouping them. Fire size is another factor affecting the model performance and the model accuracy increases with increasing fire size. The result from this study can help mine safety personnel make informed decisions during a mine fire emergency.
RESUMEN
Green innovation (GI) is an important way to build an ecological civilization and an innovative country. The study on urban green innovation (UGI) is of great significance for enriching the research on GI and rationally formulating high-quality urban development policies. The green patent data obtained using a web crawler was used to represent the level of UGI. The spatiotemporal evolution and influencing factors of UGI in China were analyzed by standard deviation ellipses, spatial autocorrelation, and Geodetector. The research shows that: From 2005 to 2020, the level of UGI in China tended to rise rapidly. The center of gravity of UGI in China was located in the southeast of China's geometric center and tended to move to the south and west. The standard deviation ellipse was distributed in a "northeast-southwest" pattern, the area was gradually shrinking, and the length of the two semi-axes was shortening. UGI in China showed obvious global and local spatial autocorrelations. The degree of global spatial autocorrelation was gradually increasing. Among the types of local spatial autocorrelation, the largest number of low-low agglomeration cities was mainly located in the northwest and southwest part of China, while high-high agglomeration cities were distributed in Beijing-Tianjin-Hebei, Yangtze River Delta, and Pearl River Delta. The government intervention expressed by the proportion of scientific and technological expenditure in fiscal expenditure and environmental regulation is the dominant factor affecting UGI.