Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infiltration.

This research aims to identify the key fatty acid beta-oxidation (FAO) genes that are altered in kidney renal clear cell carcinoma (KIRC) and to analyze the role of these genes in KIRC. The Gene Expression Omnibus (GEO) and FAO datasets were used to identify these key genes. Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain (ACADM) between KIRC and non-cancer samples. The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features. The diagnostic performance of ACADM for KIRC was assessed using a diagnostic receiver operating characteristic (ROC) curve. The co-expressed genes of ACADM were identified in LinkedOmics database, and their function and pathway enrichment were analyzed. The correlation between ACADM expression level and immune infiltration was analyzed by Gene Set Variation Analysis (GSVA) method. Additionally, the proliferation, migration, and invasion abilities of KIRC cells were assessed after overexpressing ACADM. Following differential analysis and intersection, we identified six hub genes, including ACADM. We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic effect (AUC = 0.916). Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis. According to correlation analysis, a variety of clinical features were associated with the expression level of ACADM. By analyzing the infiltration level of immune cells, we found that ACADM may be related to the enrichment of immune cells. Finally, ACADM overexpression inhibited proliferation, migration, and invasion of KIRC cells. In conclusion, our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis. These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC, offering a reference for clinicians in diagnosis and treatment.

Factors associated with balance impairments in the community-dwelling elderly in urban China.

BACKGROUND: Identification of factors relevant to balance performance impairments in the elderly population was critical for developing effective interventions and preventions. However, there have been very limited data available based on large scale studies. The present study identified factors that independently contributed to performance impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and individual items. METHODS: A total of 1984 community-dwelling Chinese elderly from urban areas of Shanghai were recruited. Information on demographic characteristic, exercise, and health status were collected with a face-to-face interview. Balance performances were assessed on site by trained investigators based on the X16 balance testing scale. To identify the effectors, ordinal logistic regression analysis was applied for overall balance, static balance, postural stability, and dynamic balance. Binary logistic regression analysis was used for 16 items. RESULTS: The community-dwelling elderly residents were aged from 60 to 97 years old. With increases of age, risks of impairments in overall balance increased gradually (ORs from 1.26 to 3.20, all P < 0.01). In the elderly with overweight and obesity, there was higher proportion of balance impairments compared to the elderly with normal BMI (OR = 1.26, P < 0.001). Regular exercise every week was associated with reduced risks of balance impairments (ORs from 0.63 to 0.73, all P < 0.001). Presences with vision lesion (ORs from 1.28 to 1.59, all P < 0.001), moderate hearing impairment (OR = 1.54, P < 0.001), somesthesis dysfunction (ORs from 1.59 to 13.26, all P < 0.001), and cerebrovascular disease (OR = 1.45, P = 0.001) were related to increased risks of balance impairments. Likewise, age, exercise, vision, hearing, somesthesis, and cerebrovascular disease were significantly associated with static balance, postural stability, and dynamic balance. Both overweight and obesity and underweight were associated with higher proportions of dynamic balance impairments. Regular exercise was significantly related to reduced risks of impairments in 15 out of the 16 items. CONCLUSIONS: In the elderly, age, overweight and obesity, exercise, vision, hearing, somesthesia, and cerebrovascular disease were dominant factors associated with impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and most individual items. TRIAL REGISTRATION: Not applicable.

High C1QTNF1 expression mediated by potential ncRNAs is associated with poor prognosis and tumor immunity in kidney renal clear cell carcinoma.

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.

Three-dimensional Ni foam supported NiCoO2@Co3O4 nanowire-on-nanosheet arrays with rich oxygen vacancies as superior bifunctional catalytic electrodes for overall water splitting.

Earth abundant transition metal oxide (EATMO)-based bifunctional catalysts for overall water splitting are highly desirable, but their performance is far from satisfactory due to low intrinsic activities of EATMOs toward electrocatalysis of both oxygen and hydrogen evolution reactions and poor electron transfer and transport capabilities. A three-dimensional (3-D) Ni-foam-supported NiCoO2@Co3O4 nanowire-on-nanosheet heterostructured array with rich oxygen vacancies has been synthesized, showing OER activity superior to most reported catalysts and even much higher than Ru and Ir-based ones and HER activity among the highest reported for non-noble-metal-based catalysts. The excellent activities are ascribed to the highly dense, ultrathin nanowire arrays epitaxially grown on an interconnected layered nanosheet array greatly facilitating electron transfer and providing numerous electrochemically accessible active sites and the high content of oxygen vacancies on nanowires greatly promoting OER and HER. When adopted as bifunctional electrodes for overall water splitting, this heterostructure shows an overvoltage (at 10 mA cm-2) lower than most reported electrolyzers and high stability. This work not only creates a 3-D EATMO-based integrated heterostructure as a low-cost, highly efficient bifunctional catalytic electrode for water splitting, but also provides a novel strategy to use unique heteronanostructures with rich surface defects for synergistically enhancing electrocatalytic activities.

Comprehensive analysis of the role of CXCL family members in clear cell renal cell carcinoma.

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.

Current development of biosensing technologies towards diagnosis of mental diseases.

The biosensor is an instrument that converts the concentration of biomarkers into electrical signals for detection. Biosensing technology is non-invasive, lightweight, automated, and biocompatible in nature. These features have significantly advanced medical diagnosis, particularly in the diagnosis of mental disorder in recent years. The traditional method of diagnosing mental disorders is time-intensive, expensive, and subject to individual interpretation. It involves a combination of the clinical experience by the psychiatrist and the physical symptoms and self-reported scales provided by the patient. Biosensors on the other hand can objectively and continually detect disease states by monitoring abnormal data in biomarkers. Hence, this paper reviews the application of biosensors in the detection of mental diseases, and the diagnostic methods are divided into five sub-themes of biosensors based on vision, EEG signal, EOG signal, and multi-signal. A prospective application in clinical diagnosis is also discussed.

Sphingosine kinase 1 regulates lipid metabolism to promote progression of kidney renal clear cell carcinoma.

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.

Comparison of the effects of endoscopic submucosal dissection and laparoscopic distal radical surgery on the rehabilitation and quality of life of patients with early gastric cancer.

OBJECTIVE: This study was designed to compare the effects of endoscopic submucosal dissection (ESD) and laparoscopic distal radical surgery (LDRS) on patient rehabilitation and quality of life (QoL) in patients with early gastric cancer (GC). METHODS: The clinical data of 52 patients with early GC admitted to Wuhan Union Hospital from January 2018 to December 2020 were retrospectively analyzed. Among them, 32 patients who underwent LDRS were assigned to the laparoscopic group, and the rest of the 20 patients who underwent ESD were assigned to the endoscopic group. The two groups were compared in clinical efficacy, intraoperative blood loss, operation time, postoperative hospitalization time, gastrointestinal ventilation time and postoperative complications, and the postoperative recurrence and postoperative QoL of the two groups were evaluated and recorded. Independent risk factors for recurrence of gastric cancer were analyzed by logistics regression. RESULTS: The laparoscopic group showed a significantly lower complete resection rate than the endoscopic group (P=0.030). The endoscopic group experienced notably less intraoperative blood loss and operation time, significantly earlier time for the first anal exhaust and shorter hospitalization time in contrast to the laparoscopic group (all P<0.05). Six months after operation, the endoscopic group had notably higher MOS 36-Item Short-Form Health Survey (SF-36) scores than the laparoscopic group (P<0.001). In addition, the laparoscopic group had a notably higher total incidence rate of complications than the endoscopic group (P<0.05). Among the 52 patients, 8 patients had recurrence. According to Logistics regression analysis, tumor diameter and invasion depth were independent risk factors for recurrence (both P<0.05). CONCLUSION: With significantly better efficacy than that of LDRS, ESD is beneficial to postoperative rehabilitation and can improve the QoL of patients, and both schemes cause no significant effect on the recurrence of patients.

Meta-analysis of the efficacy and adverse drug reactions of adrenergic alpha-antagonists in treating children with ureteral calculi.

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 "<5 mm" or "5-10 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.

Establishment of a new prognostic risk model of MAPK pathway-related molecules in kidney renal clear cell carcinoma based on genomes and transcriptomes analysis.

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.

Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma.

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.

Suspension culture strategies to enrich colon cancer stem cells.

How to efficiently obtain high-purity cancer stem cells (CSCs) has been the basis of CSC research, but the optimal conditions for serum-free suspension culture of CSCs are still unclear. The present study aimed to define the optimal culture medium composition and culture time for the enrichment of colon CSCs via suspension culture. Suspension cell cultures of colon cancer DLD-1 cells were prepared using serum-free medium (SFM) containing variable concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to produce spheroids. Culture times were set at 10, 20 and 30 days. A total of nine different concentrations of EGF and bFGF were added to SFM to generate nine experimental groups. The proportions of CD44+, CD133+, and CD44+CD133+ double-positive spheroid cells were detected via flow cytometry. mRNA expression of stemness-, epithelial-mesenchymal transition- and Wnt/ß-catenin pathway-associated genes was determined via reverse transcription-quantitative PCR. Self-renewal ability was evaluated by a sphere-forming assay. Tumorigenesis was studied in vitro using a colony formation assay and in vivo via subcutaneous cell injection in nude mice. It was found that the highest expression proportions of CD133+ and CD44+ spheroid cells were observed in group (G)9 (20 ng/ml EGF + 20 ng/ml bFGF) at 30 days (F=123.554 and 99.528, respectively, P<0.001), CD133+CD44+ cells were also observed in G9 at 30 days (and at 10 days in G3 and 20 days in G6; F=57.897, P<0.001). G9 at 30 days also displayed the highest expression of Krüppel-like factor 4, leucine-rich repeat-containing G protein-coupled receptor 5, CD44, CD133, Vimentin and Wnt-3a (F=22.682, 25.401, 3.272, 7.852, 13.331 and 17.445, respectively, P<0.001) and the lowest expression of E-cadherin (F=10.851, P<0.001). G9 at 30 days produced the highest yield of cell spheroids, as determined by a sphere forming assay (F=19.147, P<0.001); colony formation assays also exhibited the greatest number of colonies derived from G9 spheroids at 30 days (F=60.767, P<0.01), which also generated the largest mean tumor volume in the subcutaneous tumorigenesis xenograft model (F=12.539, P<0.01). In conclusion, 20 ng/ml EGF + 20 ng/ml bFGF effectively enriched colon CSCs when added to suspension culture for 30 days, and conferred the highest efficiency compared with other combinations.

Emerging landscape of circFNDC3B and its role in human malignancies.

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.

NEK2 is associated with poor prognosis of clear cell renal cell carcinoma and promotes tumor cell growth and metastasis.

BACKGROUND: Never in Mitosis gene-A(NIMA)-related Kinase 2 (NEK2) is a critical player in themitotic processes. NEK2 is highly expressed in many kindsof human cancers and has been shown toparticipatein drug resistance, tumorigenesis, and tumor progression. However, the expression or function of NEK2 in clear cell renal cell carcinoma (ccRCC)hasnot yet been investigated. METHODS: Weused TCGA databaseto study the NEK2 expression in ccRCC. The expression of NEK2 in tumor tissuesand adjacent tissueswas examined by immunohistochemistry. We also analysed the correlation between NEK2 expression and clinical parametersofccRCC. The mRNA and protein level of NEK2 expression were semi-quantifiedby qRT-PCR and western blotting analysis. Following NEK2 knockdown by RNA interference in Caki-1cells, whileNEK2 overexpression in A489 cells, CCK8and transwell assay was used to confirmtheproliferation, migration and invasion, respectively.Finally, our in vivo study were carried out using nudemice to establish mouse model for kidney cancer. RESULTS: We observed elevated expression of NEK2 both in ccRCCtumor tissues and cell lines. Together with clinical and pathological features, our analysis indicated a clear association of clinical outcomes between ccRCC patients with high and lowNEK2expression. Our in vitro studies demonstratedthat NEK2 knockdowninhibits the proliferation,migrationand invasion of Caki-1cells, oppositely, overexpressionof NEK2 promotes the proliferation, migrationand invasion of A489cells.In the end, our animal study demonstrated that deletion of NEK2 expression could impair tumor growth. CONCLUSION: Our data suggestedthat NEK2wasimportant inregulating ccRCC cell proliferation and metastasis, and indicated NEK2as a potentially important target for the treatment ofccRCC.

Effectiveness of WeChat-group-based parental health education in preventing unintentional injuries among children aged 0-3: randomized controlled trial in Shanghai.

BACKGROUND: Unintentional injuries to children are a major public health problem. The online social media is a potential way to implement health education for caregivers in online communities. Using WeChat, a free and popular social media service in China, this study evaluated the effectiveness of social online community-based parental health education in preventing unintentional injuries in children aged 0-3. METHODS: We recruited 365 parents from two community health centers in Shanghai and allocated them into intervention and control groups randomly. Follow-up lasted for one year. The intervention group received and followed their WeChat group and a WeChat official account for dissemination of reliable medical information. The control group received only the WeChat group. RESULTS: Between the intervention and control groups, changes in unintentional injuries (OR = 1.71, 95% CI: 1.02-2.87, P = .04), preventability (ß = 0.344, 95% CI: 0.152-0.537, P < .001), daily supervision behavior (ß = 0.503, 95% CI: 0.036-0.970, P = .04), and behaviors for preventing specific injuries (ß = 2.198, 95% CI: 1.530-2.865, P < .001) were significantly different, and change in first-aid skills for treating a tracheal foreign body were nearly significant (P = .06). CONCLUSIONS: The WeChat-group-based parental health education can reduce the occurrence of unintentional child injuries by improving parents' skills, beliefs, and behaviors. Online social communities promote health education and reduce unintentional injuries among children. TRIAL REGISTRATION: ChiCTR1900020753. Registered on January 17, 2019.

The Role of ERBB Signaling Pathway-Related Genes in Kidney Renal Clear Cell Carcinoma and Establishing a Prognostic Risk Assessment Model for Patients.

Objective: We aimed to investigate the potential role of ERBB signaling pathway-related genes in kidney renal clear cell carcinoma (KIRC) and establish a new predictive risk model using various bioinformatics methods. Methods: We downloaded the KIRC dataset and clinicopathological information from The Cancer Genome Atlas database. Univariate Cox analysis was used to identify essential genes significantly associated with KIRC progression. Next, we used the STRING website to construct a protein-protein interaction network of ERBB signaling pathway-related molecules. We then used the least the absolute shrinkage and selection operator (LASSO) regression analysis to build a predictive risk model for KIRC patients. Next, we used multiple bioinformatics methods to analyze the copy number variation, single-nucleotide variation, and overall survival of these risk model genes in pan-cancer. At last, we used the Genomics of Drug Sensitivity in Cancer to investigate the correlation between the mRNA expression of genes associated with this risk model gene and drug sensitivity. Results: Through the LASSO regression analysis, we constructed a novel KIRC prognosis-related risk model using 12 genes: SHC1, GAB1, SOS2, SRC, AKT3, EREG, EIF4EBP1, ERBB3, MAPK3, transforming growth factor-alpha, CDKN1A, and PIK3CD. Based on this risk model, the overall survival rate of KIRC patients in the low-risk group was significantly higher than that in the high-risk group (p = 1.221 × 10-15). Furthermore, this risk model was associated with cancer metastasis, tumor size, node, stage, grade, sex, and fustat in KIRC patients. The receiver operating characteristic curve results showed that the model had better prediction accuracy. Multivariate Cox regression analysis showed that the model's risk score was an independent risk factor for KIRC. The Human Protein Atlas database was used to validate the protein expression of risk model-associated molecules in tumors and adjacent normal tissues. The validation results were consistent with our previous findings. Conclusions: We successfully established a prognostic-related risk model for KIRC, which will provide clinicians with a helpful reference for future disease diagnosis and treatment.

ARL4C Regulates the Progression of Clear Cell Renal Cell Carcinoma by Affecting the Wnt/ß-Catenin Signaling Pathway.

Purpose: To investigate the expression of the ADP-ribosylation factor (ARF)-like proteins (ARLs) and ARL4C in clear cell renal cell carcinoma (ccRCC) based on bioinformatics analysis and experimentally determine the effect and mechanism of ARL4C on cellular properties involved in ccRCC progression. Methods: After downloading the data of cancer patients from the TCGA database, we used various bioinformatics analysis websites and methods to analyze the expression and function of ARLs and ARL4C. The differential expression of ARL4C in clinical renal cancer tissues versus adjacent normal tissues was further verified using immunohistochemistry and real-time quantitative reverse-transcription (qRT-PCR). qRT-PCR was used to explore the expression of ARL4C mRNA in normal renal cells versus different ccRCC cell lines, and the protein expression of ARL4C was further verified using western blotting. CCK-8, colony formation, and EdU assays were used to determine the effect of ARL4C knockdown on ccRCC cell proliferation. We also used wound healing and Transwell assays to analyze the changes in ccRCC cell migration and invasion following ARL4C knockdown. Finally, we used western blotting to probe the molecular mode of action of ARL4C in ccRCC cells after exposure to Wnt signaling pathway agonists. Results: Biological function analysis showed that methylation of ARL4C and changes in immune cell infiltration and targeted drug sensitivity caused by altered ARL4C expression affected the prognosis of ccRCC. Further bioinformatics analysis suggested that the expression of ARL4C mRNA was increased in ccRCC, and this was associated with a poor prognosis in ccRCC patients. Increased expression of ARL4C was further verified using qRT-PCR and western blotting of human ccRCC tissue samples. Downregulation of ARL4C significantly inhibited the proliferation, migration, and invasion of ccRCC cells, and activation of the Wnt/ß-catenin pathway promoted the expression of ARL4C. As an essential downstream effector of the Wnt signaling pathway, ARL4C increased the expression of cyclin D1 and c-myc, thereby increasing the ability of the cells to undergo epithelial-mesenchymal transition (EMT) and ccRCC progression. Conclusions: As a critical factor in the Wnt/ß-catenin pathway, ARL4C regulates EMT and progression in ccRCC.

AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma.

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.

Au-Se bonded nanoprobe for prostate specific antigen detection in serum.

The detection of prostate specific antigen (PSA) in serum can realize early diagnosis of prostate cancer and prevent the occurrence of prostate tumors, as well as offering guidance during the therapy. Herein, a Au-Se bonded nanoprobes that can specifically detect PSA was designed and constructed. The peptide chains that can be specifically cleaved by PSA were firstly functionalized with fluorescent dye and selenol, and then bind to the Au nanoparticles to produce the probe. The dye's fluorescence was quenched due to the FRET effect, but recovered by PSA's cutting. The nanoprobe can detect PSA in serum with extraordinary anti-interference ability against other proteins (detection range 1-40 ng/mL). This work provides a new method for the detection of PSA in serum, and has potential guiding significance for clinical PSA detection.