Integrated single-cell and bulk characterization of branched chain amino acid metabolism-related key gene BCAT1 and association with prognosis and immunogenicity of clear cell renal cell carcinoma.

BACKGROUND: The relationship between clear cell renal cell carcinoma (ccRCC) and branched-chain amino acids (BCAA) metabolism has yet to be thoroughly explored. METHODS: The BCAA metabolism-related clusters were constructed using non-negative matrix factorization (NMF). The features of BCAA metabolism in ccRCC were evaluated by building a prognostic model using least absolute shrinkage and selection operator (LASSO) regression algorithm. Real-time quantitative PCR (RT-qPCR) was employed to analyze differential expression of branched-chain amino acid transaminase 1 (BCAT1) between cancer and paracancer tissues and between different cell lines. Cell counting kit-8, wound healing and Transwell chamber assays were conducted to determine changes in proliferative and metastatic abilities of A498 and 786-O cells. RESULTS: Two BCAA metabolism-related clusters with distinct prognostic and immune infiltration characteristics were identified in ccRCC. The BCAA metabolic signature (BMS) was capable of distinguishing immune features, tumor mutation burden, responses to immunotherapy, and drug sensitivity among ccRCC patients. RT-qPCR revealed overexpression of BCAT1 in ccRCC tissues and cell lines. Additionally, single-gene RNA sequencing analysis demonstrated significant enrichment of BCAT1 in macrophages and tumor cells. BCAT1 played tumor-promoting role in ccRCC and was closely associated with immunosuppressive cells and checkpoints. BCAT1 promoted ccRCC cell proliferation and metastasis. CONCLUSIONS: The BMS played a crucial role in determining the prognosis, tumor mutation burden, responses to immunotherapy and drug sensitivity of ccRCC patients, as well as the immune cell infiltration features. BCAT1 was linked to immunosuppressive microenvironments and may offer new sights into ccRCC immunotherapeutic targets.

Identification of Crotonylation Metabolism Signature Predicting Overall Survival for Clear Cell Renal Cell Carcinoma.

Background: Immunotherapy shows promise in treating cancer by leveraging the immune system to combat cancer cells. However, the influence of crotonylation metabolism on the prognosis and tumor environment in ccRCC patients is not fully understood. Methods: We conducted various systematic analyses, including prognosis and cluster analyses, to investigate the role of KAT2A in immunotherapy. We used qRT-PCR to compare KAT2A expression in cancer and adjacent tissues and among different cell lines. Additionally, we employed Cell Counting Kit-8, wound healing, and Transwell chamber assays to assess changes in the proliferative and metastatic ability of A498 and 786-O cells. Results: We identified three clusters related to crotonylation metabolism, each with distinct prognosis and immune characteristics in ccRCC. We categorized CT1 as immune-inflamed, CT2 as immune-excluded, and CR3 as immune-desert. A new system, CRS, emerged as an effective predictor of patient outcomes with differing immune characteristics. Moreover, qRT-PCR revealed elevated KAT2A levels in ccRCC tissues and cell lines. KAT2A was found to promote ccRCC and correlate significantly with immunosuppressive elements and checkpoints. Reducing KAT2A expression hindered ccRCC cell growth and metastasis. Conclusion: Our study highlights the critical role of crotonylation metabolism in cancer development and progression, particularly its link to poor prognosis. CRS proves to be an accurate predictor of patient outcomes and immune features in ccRCC. KAT2A shows strong associations with clinical factors and the immunosuppressive environment, suggesting potential for innovative immunotherapies in ccRCC treatment.

Identification and validation of DLX4 as a prognostic and diagnostic biomarker for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a lethal cancer, and biomarkers for exact diagnosis and predicting prognosis are urgently needed. The present study aimed to determine the roles of distal-less homeobox (DLX) family genes in ccRCC. The clinicopathological and mRNA expression data of patients with ccRCC were derived from The Cancer Genome Atlas database. Kaplan-Meier curves, univariate and multivariate Cox hazard analyses, in addition to receiver operator characteristic curves were used to evaluate the prognostic and diagnostic values. A single-sample gene set enrichment analysis was used to quantify the infiltration levels of immune cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were conducted to examine the expression levels of DLX4 in tumor and adjacent tissue; the results demonstrated that DLX4 was highly expressed in ccRCC tissues compared with normal renal tissues. Furthermore, DLX4 expression was associated with tumor stage and grade. High proportions of males, advanced pathological stage, higher tumor grade and T, N and M stage were also observed in the high DLX4 expression group. Patients with the high DLX4 expression levels tended to have lower overall survival and disease-free survival rates compared with those with low DLX4 expression. DLX4 expression also showed favorable diagnostic efficiency in ccRCC patients. Based on functional enrichment analysis, cell cycle related pathways, epithelial-mesenchymal transition, glycolysis and inflammatory response were associated with the expression levels of DLX4. Furthermore, DLX4 expression was revealed to be associated with tumor immunosuppressive microenvironment. Overall, the expression level of DLX4 may be considered a novel prognostic indicator in ccRCC and a specific diagnostic biomarker for patients with ccRCC.

Accumulation of Galactinol and ABA Is Involved in Exogenous EBR-Induced Drought Tolerance in Tea Plants.

Drought stress severely limits growth and causes losses in the yield of tea plants. Exogenous application of 24-epibrassinolide (EBR) positively regulates drought responses in various plants. However, whether EBR could contribute to drought resistance in tea plants and the underlying mechanisms has not been investigated. Here, we found that EBR application is beneficial for the drought tolerance of tea plants. The transcriptome results revealed that EBR could contribute to tea plant drought resistance by promoting galactinol and abscisic acid (ABA) biosynthesis gene expression. The content of galactinol was elevated by EBR and EBR-responsive CsDof1.1 positively regulated the expression of the galactinol synthase genes CsGolS2-1 and CsGolS2-2 to contribute to the accumulation of galactinol by directly binding to their promoters. Moreover, exogenous EBR was found to elevate the expression of genes related to ABA signal transduction and stomatal closure regulation, which resulted in the promotion of stomatal closure. In addition, EBR-responsive CsMYC2-2 is involved in ABA accumulation by binding to the promoters CsNCED1 and CsNCED2 to activate their expression. In summary, findings in this study provide knowledge into the transcriptional regulatory mechanism of EBR-induced drought resistance in tea plants.

A higher TyG index is related with a higher prevalence of erectile dysfunction in males between the ages 20-70 in the United States, according to a cross-sectional research.

Objective: This study aims to investigate the relationship between triglyceride glucose index (TyG) and erectile dysfunction (ED) among United States (US) adult males. Methods: A logistic regression analysis, subgroup analysis, and the computation of the dose-response curve were used to investigate the relationship between TyG index and ED prevalence among participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) database. Results: After adjusting for all confounders, each unit increase in TyR index was associated with a 25 percent increase in ED prevalence (OR=1.25, 95%CI:1.03, 1.52), and stratified analysis showed that elevated TyG index was associated with increased ED prevalence in the 50-year old group (OR=1.35, 95% CI:1.05, 1.74), the Mexican-American group (OR=1.50, 95% CI:1.00, 2.23) and BMI 25-29.9 kg/m2 (OR=1.48, 95% CI:1.08, 2.01). The dose-response curve demonstrated a positive linear connection between the TyG index and the risk of ED. Conclusion: It has been shown that a higher TyG index is associated with a higher prevalence of erectile dysfunction. Although the causal relationship is not clear, it still deserves clinical attention.

AC010973.2 promotes cell proliferation and is one of six stemness-related genes that predict overall survival of renal clear cell carcinoma.

Extensive research indicates that tumor stemness promotes tumor progression. Nonetheless, the underlying roles of stemness-related genes in renal clear cell carcinoma (ccRCC) are unclear. Data used in bioinformatics analysis were downloaded from The Cancer Genome Atlas (TCGA) database. Moreover, the R software, SPSS, and GraphPad Prism 8 were used for mapping and statistical analysis. First, the stemness index of each patient was quantified using a machine learning algorithm. Subsequently, the differentially expressed genes between high and low stemness index were identified as stemness-related genes. Based on these genes, a stable and effective prognostic model was identified to predict the overall survival of patients using a random forest algorithm (Training cohort; 1-year AUC: 0.67; 3-year AUC: 0.79; 5-year AUC: 0.73; Validation cohort; 1-year AUC: 0.66; 3-year AUC: 0.71; 5-year AUC: 0.7). The model genes comprised AC010973.2, RNU6-125P, AP001209.2, Z98885.1, KDM5C-IT1, and AL021368.3. Due to its highest importance evaluated by randomforst analysis, the AC010973.2 gene was selected for further research. In vitro experiments demonstrated that AC010973.2 is highly expressed in ccRCC tissue and cell lines. Meanwhile, its knockdown could significantly inhibit the proliferation of ccRCC cells based on colony formation and CCK8 assays. In summary, our findings reveal that the stemness-related gene AC01097.3 is closely associated with the survival of patients. Besides, it remarkably promotes cell proliferation in ccRCC, hence a novel potential therapeutic target.

Exposure to Dibutyl Phthalate and Reproductive-Related Outcomes in Animal Models: Evidence From Rodents Study.

Background: Dibutyl phthalate (DBP) was an endocrine disruptor, which may lead to cancer and affects reproductive function when accumulated in the body. But the precise role of DBP in the reproductive system remained controversial. Objective: We employed the meta-analysis to explore the relationship between DBP and reproductive-related outcomes. Methods: We searched relevant literature in PubMed, EMBASE, and Web of Science databases. The standardized mean differences (SMDs) and their 95% CIs were measured by random-effects models. Funnel plots and Egger's regression test were applied to assess publication bias. Results: Finally, 19 literatures were included in this research. The outcomes revealed that DBP was negatively correlated with reproductive organs weight (testis weight: SMD: -0.59; 95% Cl: -1.23, -0.23; seminal vesicles weight: SMD: -0.74; 95% Cl: -1.21, -0.27; prostate weight: SMD: -0.46; 95% Cl: -0.76, -0.16) and sperm parameters (sperm morphology: SMD: 1.29; 95% Cl: 0.63, 1.94; sperm count: SMD: -1.81; 95% Cl: -2.39, -1.23; sperm motility: SMD: -1.92; 95% Cl: -2.62, -1.23). Conclusion: Our research demonstrated that DBP may be negatively associated with reproductive-related indicators, especially at Gestation exposure period and middle dose (100-500 mg/kg/day).

Knowledge, attitudes, clinical practice and perceived barriers with nutrition support among physicians and nurses in the emergency department: A national cross-sectional survey.

OBJECTIVE: To explore the current status of knowledge, attitudes, clinical practice and barriers in nutrition support amongst physicians and nurses working in Chinese Emergency Departments (EDs), and the relationship between their demographic characteristics and knowledge and attitudes regarding nutrition support. METHODS: A 34 item survey was developed, validated and distributed nationally to ED physicians and nurses from 1st April to 1st May 2018. RESULTS: A total of 1234 respondents completed and returned the survey. Knowledge of nutrition support was moderate (mean: 6.70/10) and differed significantly based on demographic characteristics (e.g. age, staff type). Attitudes was very positive (4.15/5), more so among nurses compared to physicians. Only few (5.6%) respondents reportedly assessed nutritional condition for all patients. The most common barriers to optimize nutrition support were being too busy, lack of standardized protocol specific to ED, and lack of teamwork and coordination. CONCLUSION: In a subset of physicians and nurses working in Chinese EDs, limited knowledge but positive attitudes toward nutrition support was evident. Recommendations to optimize evidence-based nutritional support practice in the ED include initiating, implementing and sustaining training regarding nutrition support, establishing, implementing and evaluating a standardized protocol, and enhancing interdisciplinary coordination.

Correlation between crowdedness in emergency departments and anxiety in Chinese patients.

BACKGROUND: Emergency department (ED) overcrowding is a severe health care concern, while anxiety and depression rates among ED patients have been reported to be substantially higher compared to the general population. We hypothesized that anxiety due to over crowdedness may lead to adverse events in EDs. AIM: To investigate correlations between crowdedness in EDs and anxiety of patients and nurses, and to identify factors affecting their anxiety. METHODS: In this prospective observational study, a total 43 nurses and 389 emergency patients from two tier III hospitals located in Beijing were included from January 2016 to August 2017. Patients were grouped into inpatients when they were hospitalized after diagnoses, or into outpatients when they were discharged after treatments. The State Trait Anxiety Inventory (STAI Form Y) questionnaire was used to investigate patient and nurse anxieties, while crowdedness of EDs was evaluated with the National Emergency Department Over Crowding Score. RESULTS: The present results revealed that state anxiety scores (49.50 ± 6.00 vs 50.80 ± 2.80, P = 0.005) and trait anxiety scores (45.40 ± 5.70 vs 46.80 ± 2.70, P = 0.002) between inpatients (n = 173) and outpatients (n = 216) were significantly different, while the state anxiety of nurses (44.70 ± 5.80) was different from those of both patient groups. Generalized linear regression analysis demonstrated that multiple factors, including crowdedness in the ED, were associated with state and trait anxieties for both inpatients and outpatients. In addition, there was an interaction between state anxiety and trait anxieties. However, multivariable regression analysis showed that while overcrowding in the ED did not directly correlate with patients' and nurses' anxiety levels, the factors that did correlate with state and trait anxieties of inpatients were related to crowdedness. These factors included waiting time in the ED, the number of patients treated, and the number of nurses in the ED, whereas for nurses, only state and trait anxieties correlated significantly with each other. CONCLUSION: Waiting time, the number of patients treated, and the number of nurses present in the ED correlate with patient anxiety in EDs, but crowdedness has no effect on nurse or patient anxiety.

PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer: Evidence from meta-analysis.

Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (-842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity.

[Variation of nestin expression in SD rat eyes in different stages of postnatal development].

OBJECTIVE: To observe the position and quantity of nestin expression in SD rat eyes in different stages of postnatal development. METHODS: Immunocytochemical method was used to identify nestin expression in the eyes of SD rats of 1 to 30 days old. RESULTS: Nestin expression was detected in the retina and extraocular muscles of SD rats. The expression varied with the time of postnatal development, distributing in the entire retina layers in earlier stages and confined in the nerve fiber layer in later stages. The quantities of nestin expression in the extraocular muscles decreased gradually with growth. CONCLUSION: Nestin expression in the retinas and extraocular muscles of SD rats decreases during the postnatal development.