Genetic characterization of 2 Ceutorhynchus (Coleoptera: Curculionidae) weevils with mitogenomes and insights into the phylogeny and evolution of related weevils.

The rape stem weevil (Ceutorhynchus asper Roel.) and its close relatives primarily breed on cruciferous plants and cause severe damage to rapeseed production. However, their genetic and molecular information is still scarce. Here, we generated mitogenomes for both C. asper and Ceutorhynchus albosuturalis. The lengths of the 2 mitochondrial genomes are 14,207 bp (C. asper) and 15,373 bp (C. albosuturalis), and both weevils exhibit identical numbers of protein-coding genes with the absence of trnI. A + T contents for both mitogenomes are high (80% and 79.9%, respectively). Haplotype and genetic distance analyses showed that the genetic differentiation of C. asper populations in northwestern China is low. Based on 5 datasets from mitogenomes, phylogenetic analyses with maximum-likelihood and Bayesian methods show that both species (C. asper and C. albosuturalis) fall in the CCCMS clade (Curculioninae, Conoderinae, Cossoninae, Molytinae, and Scolytinae) of Curculionidae and belong to clades H and I of the genus Ceutorhynchus, respectively. Larvae of the clade H weevils mainly are borers in petioles or stems of cruciferous plants, while larvae of the clade I weevils mainly inhabit the fruits of the same plants, suggesting that ecological niche specialization can play a critical role in the diversification of Ceutorhynchus species. This study generates baseline molecular and genetic information for future research of Ceutorhynchus-related taxa and provides insights into the phylogeny and evolution of Curculionidae.

Effect of Interfacial Modification on the Low-Temperature Fatigue Properties of Polymer/MXene Flexible Pressure Sensors.

Maintaining an excellent force-electric response under cyclic bending at low temperatures is still challenging for resistive-type electrically conductive polymer composite-based pressure sensors. In this study, the effect of low temperature on the fatigue failure of flexible MXene/polymer pressure sensors was systematically investigated through the silane functionalization of MXene nanosheets embedded with different polymer matrixes. The results show that the MXene/polymer interfaces are the primary factors affecting the temperature-dependent bending fatigue of the Cu/MXene/polymer/Cu sensor. Using finite element analysis and theoretical calculations, we reveal that the MXene/polymer interfaces are affected by free volume changes and the molecular chain motion under different temperatures. At room temperature, the well-distributed free volume in the polydimethylsiloxane (PDMS) matrix permits local segmental mobility that promotes the affinity between the polymer and MXene. As the temperature decreases, the free volume in the matrix shrinks with less space left for molecular chains to slide relatively, weakening the polymer/MXene interfacial bonding strength. However, for PDMS/MXene sensors with the interface modified using the silane coupling agent KH550, the nanoconstrained structure formed by strong hydrogen bonds and covalent bonds at the PDMS/MXene interface can hinder the mobility of polymer chains, which greatly helps to dissipate the inter/intrachain friction. It thus alleviates the debonding energy dissipation during cyclic bending at subzero temperatures.

The causal relationship between gut microbiota and leukemia: a two-sample Mendelian randomization study.

Background: The association between gut microbiota and leukemia has been established, but the causal relationship between the two remains unclear. Methods: A bidirectional two-sample Mendelian randomization (MR) was used to analyze the causal relationship between gut microbiota and leukemia. Microbiome data (n = 14,306) and leukemia (n = 1,145) data were both sourced from European populations. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on several criteria. We employed various MR methods, such as the inverse variance weighted (IVW) method, to evaluate the causal effect between exposure and outcomes and conducted sensitivity analyses to validate the heterogeneity and pleiotropy of the instrumental variables. Results: 5,742 qualified instrumental variables were included. In the primary MR results, a total of 10 gut microbial taxa were associated with leukemia risk. Genus Blautia and genus Lactococcus are risk factors for acute lymphoblastic leukemia [genus Blautia odds ratio (OR): 1.643, 95% confidence interval (CI): 1.592 ~ 1.695, Adjusted p < 0.001; genus Lactococcus OR: 2.152, 95% CI: 1.447 ~ 3.199, Adjusted p = 0.011]. Genus Rikenellaceae RC9 gut group, genus Anaerostipes, genus Slackia, and genus Lachnospiraceae ND3007 group are risk factors for acute myeloid leukemia [genus Rikenellaceae RC9 gut group OR: 1.964, 95% CI: 1.573 ~ 2.453, Adjusted p < 0.001; genus Anaerostipes OR: 2.515, 95% CI: 1.503 ~ 4.209, Adjusted p = 0.017; genus Slackia OR: 2.553, 95% CI: 1.481 ~ 4.401, Adjusted p = 0.022; genus Lachnospiraceae ND3007 group OR: 3.417, 95% CI: 1.960 ~ 5.959, Adjusted p = 0.001]. Genus Ruminococcaceae UCG011 and genus Ruminococcaceae UCG014 were risk factors for chronic myeloid leukemia (genus Ruminococcaceae UCG011 OR: 2.010, 95% CI: 1.363 ~ 2.963, Adjusted p = 0.044; genus Ruminococcaceae UCG014 OR: 3.101, 95% CI: 1.626 ~ 5.915, Adjusted p = 0.044). Genus Slackia was a protective factor for acute lymphoblastic leukemia (genus Slackia OR: 0.166, 95% CI: 0.062 ~ 0.443, Adjusted p = 0.017). Family Acidaminococcaceae was a protective factor for acute myeloid leukemia (family Acidaminococcaceae OR: 0.208, 95% CI: 0.120 ~ 0.361, Adjusted p < 0.001). Genus Desulfovibrio was a protective factor for chronic lymphoblastic leukemia (genus Desulfovibrio OR: 0.581, 95% CI: 0.440 ~ 0.768, Adjusted p = 0.020). Sensitivity analysis revealed no heterogeneity or pleiotropy between SNPs. Conclusion: This study revealed the causal relationship between the gut microbiota and leukemia, and identified potential pathogenic bacteria and probiotic taxa associated with the onset of leukemia. This research may aid in the early detection of various types of leukemia and offer a new direction for the prevention and treatment of leukemia.

Distinguishing anaerobic digestion from electrochemical anaerobic digestion: Metabolic pathways and the role of the microbial community.

In this study, we explored why electrochemical anaerobic digestion (EAD) results in higher methane conversion and lower CO2 emissions than anaerobic digestion (AD). Single-chamber AD and EAD reactors were used in this experiment, and the temperature was set as the disturbance factor. Current, pH, electrode potential, gas content, and microbial community were used as indicators for our analysis. Flux balance analysis (FBA) and high-pass next-generation sequencing (NGS) were used to explore the relationships between AD and EAD methane-producing metabolic fluxes and microorganisms. The results showed that the average methane fluxes were 22.27 (AD) and 29.65 (EAD). Compared with AD, EAD had improved hydrogen-dependent CO2 reduction pathway. Trichloromonas was the dominant electricity-producing microorganism on the EAD anode film, which was closely related to the H2 flux at the cathode. Oscillibacter and Syntrophomonas were the dominant bacteria in the fermentation broth, specific to EAD. The abundance of Oscillibacter was positively correlated with the H2 flux, and the presence of Oscillibacter enhanced CO2 reduction by hydrogen. Methanosaeta was the only dominant methanogenic bacterium in AD and EAD, and its abundance was higher in the experimental group with a greater methane flux.

Assessing the Land Reclamation Suitability of Beam Fabrication and Storage Yard in Railway Construction: An AHP-MEA Method.

Railway construction contributes to socio-economic development but causes the occupation and destruction of land resources. How to effectively restore the temporary land and achieve efficient and rational reuse therefore becomes particularly important. The beam fabrication and storage yard (BFSY), as a large temporary facility during railway construction, occupies a large area of land. However, BFSYs damage the land in the way of pressing and may harden the ground to a high degree due to the use of high-density pile foundations, adversely affecting the soil properties. Therefore, this research aims to develop a model for evaluating the land reclamation suitability (LRS) of BFSY. The LRS evaluation indicator system of BFSY was firstly constructed based on the literature review and expert interviews. Then, an indicator-based model for assessing the LRS of BFSY was developed by integrating the analytic hierarchy process (AHP) model and the matter-element analysis (MEA) model. A case project in China was chosen to demonstrate and validate the developed model, and results show that the proposed model can rationally evaluate the LRS of BFSY in railway construction. The findings of this research enrich the knowledge system of sustainable railway construction and guide construction managers to conduct practical suitability assessments of land reclamation.

Relationship between serum fibroblast growth factor 19 and vascular endothelial growth factor and soluble klotho protein in type 1 diabetic children.

BACKGROUND: Fibroblast growth factor 19 (FGF19) takes part in maintaining the balance of glycolipids and may be involved in complications of type 1 diabetes(T1D) in children. This study aimed at at evaluating the relationship among the levels of serum FGF19 and vascular endothelial growth factor(VEGF)and soluble klotho protein(sklotho) in type 1 diabetic children. METHODS: In a cross-section single center study samples were obtained from 96 subjects: 66 T1D and 30 healthy children.Serum FGF19 and VEGF and sklotho concentrations were measured by ELISA. And 66 type 1 diabetes participants were divided into two groups according to T1D duration or three groups according to HbA1c.Furthermore,we compared the serum levels of FGF19 and VEGF and sklotho in different groups. RESULTS: The concentration of FGF19 was lower in T1D than in the controls(226.52 ± 20.86pg/mu vs.240.08 ± 23.53 pg/L, p = 0.03),while sklotho was also lower in T1D than in the controls (2448.67 ± 791.92pg/mL vs. 3083.55 ± 1113.47pg/mL, p = 0.011). In contrast, VEGF levels were higher in diabetic patients than in controls (227.95 ± 48.65pg/mL vs. 205.92 ± 28.27 pg/mL, p = 0.016). In T1D, FGF19 and VEGF and sklotho was not correlated with the duration of diabetes. FGF19 and VEGF and sklotho were correlated with HbA1c (r=-0.349, p = 0.004 and r = 0.302, p = 0.014 and r=-0.342, p = 0.005, respectively), but not with blood glucose and lipid. Among subjects in the T1D group, concentrations of FGF19,VEGF and sklotho protein were different between different groups according to the degree of HbA1c(P < 0.005).Furthermore, there was a positive correlation between the serum FGF19 concentration and sklotho levels (r = 0.247,p = 0.045), and a negative correlation between the serum FGF19 concentration and VEGF level(r=-0.335,P = 0.006). CONCLUSIONS: The serum FGF19 levels have a close relation with serum VEGF levels and sklotho levels among T1D subjects. FGF19 may be involved in the development of complications in children with type 1 diabetes through interaction with VEGF and sklotho.

MicroRNA-708 suppresses the proliferation, migration, and invasion of human retinoblastoma cells by targeting RAP2B, a member of the RAS oncogene family.

Retinoblastoma generally affects children and causes permanent vision failure or even death. MicroRNAs (miRs) have recently gained much attention during recent years. The miR-708 acts as a tumor suppressor in several human cancers, but the former has not been functionally characterized in human retinoblastoma. The present study was designed to investigate the role of miR-708 in human retinoblastoma. The results showed that miR-708 is significantly (P<0.05) downregulated in retinoblastoma cell lines. MiR-708 overexpression significantly (P<0.05) inhibited retinoblastoma cell growth and proliferation by inducing apoptosis. Furthermore, retinoblastoma cells overexpressing miR-708 exhibited a markedly lower migratory rate and invasiveness compared to negative control cells. The bioinformatics and dual luciferase assay revealed a RAS oncogene family protein, RAP2B, which acts as the regulatory target and functional mediator of the molecular role of miR-708 in retinoblastoma. Together, the present study revealed the tumor suppressor role of miR-708 and pointed to the therapeutic implications of miR-708/RAP2B in the treatment of retinoblastoma.

Tropomyosin Is Potential Markers for the Diagnosis and Prognosis of Bladder Cancer.

Objective: To investigate the correlation between tropomyosin (TM) and clinical characteristics of bladder cancer. In addition, the relationship between TM and immune cell infiltration in bladder cancer was further analyzed. Methods: Based on The Cancer Genome Atlas (TCGA) database, the relationship between TM expression and clinicopathological features in bladder cancer was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of TM as a diagnostic marker for bladder cancer. Univariate and multivariate Cox regression was used to analyze the independent factors affecting the prognosis of patients with bladder cancer. The relationship between TM and immune cell infiltration was analyzed. Results: ROC curve showed that TPM1, TPM2, and TPM3 had significant diagnostic ability (AUC was 0.845, 0.848, and 0.873, respectively). The high expression of TPM1 and TPM2 is associated with poor overall and disease-specific survival in patients with bladder cancer (P < 0.05). Multivariate Cox analysis showed that age and TPM1 were independent prognostic factors. The expression levels of TPM1, TPM2, TPM3, and TPM4 in low grade bladder cancer were lower than those in high grade bladder cancer (P < 0.05). TPM1 and TPM2 are positively correlated with the infiltration of macrophages and NK cells in bladder cancer. TPM3 is positively associated with Th2. TPM4 is positively correlated with Th1 cells, macrophages, and neutrophils (P < 0.05). Conclusions: TPM1 and TPM2 are effective markers for the diagnosis of bladder cancer. TPM1 is an independent prognostic factor for bladder cancer. TM is also associated with the infiltration of various immune cells in bladder cancer. TM may have influenced the development of bladder cancer through immune inhibition.

[The relationship between methane production metabolic flux and microorganisms in a microbial electrolytic cell coupled anaerobic digestion].

In this study, voltage was used as a disturbance factor to investigate the relationship between microbial community and methane (CH4) production flux in a microbial electrolytic cell coupled anaerobic digestion (MEC-AD). Metabolic flux analysis (MFA) was used to explore the relationship between the CH4 metabolic flux produced and the microbes. The results showed that both methane production flux and hydrogen production flux changed significantly upon voltage disturbance, while the voltage disturbance had little effect on acetic acid production flux. The maximum CH4 production flux under 0.6 V disturbance was 0.522±0.051, which increased by 77% and 32%, respectively, compared with that of the control group under 1.0 V (0.295±0.013) and under 1.4 V (0.395±0.029). In addition, an average of 15.7%±2.9% of H2 (flux) was used to reduce CO2 to produce CH4 and acetic acid, and an average of 27.7%±6.9% of acetic acid (flux) was converted to CH4. Moreover, the abundance of Lachnospiraceae significantly affected the flux of acetic acid. The flux of CH4 production is positively correlated with the abundances of Petrimonas, Syntrophomonas, Blvii28, and Acinetobacter, and negatively correlated with the abundances of Tuzzerella and Sphaerochaeta. The species that affected the flux of H2 and CH4 were similar, mostly belonging to Bacteroides, Clostridium, Pseudomonas and Firmicutes. Furthermore, the interspecies interaction is also an important factor affecting the MEC-AD methanogenesis flux.

Improving Contractors' Participation of Resource Utilization in Construction and Demolition Waste through Government Incentives and Punishments.

This paper develops a simulation model for analyzing how government incentives and punishments improve contractors' participation in resource utilization of construction and demolition waste (RUCDW) based on system dynamics theory. The construction industry's long-term objective is to become more sustainable and resource-effective, and as part of this objective, generated construction and demolition waste should be recycled and resource utilized. However, most contractors have little willingness to engage in RUCDW because it increases their costs. The government thus plays a vital role in improving their participation in RUCDW through a range of educational tools such as advertisements, professional training, incentives, and punishments. Among these approaches, incentives and punishments are considered the most effective because they directly change project costs. We use the Vensim software package for numerical simulation and data collected from Suzhou, China are used to demonstrate and validate the developed model. Simulation results show that the government can improve contractors' participation in RUCDW through three kinds of incentives and punishments: (1) subsidizing RUCDW; (2) increasing landfill fees; and 3) issuing fines for illegal dumping. Comprehensive application of multiple policies has a stronger effect than single policies. The established model is therefore a valuable tool for assessing the dynamic effects of government incentives and punishments on RUCDW ahead of implementation, which can provide guidance for policymakers.

Introducing electrolysis to enhance anaerobic digestion resistance to acidification.

The phenomenon that the anaerobic system is inhibited by acid has always been a bottleneck hindering the application of anaerobic digestion (AD) technology. We tried to introduce electrolysis into AD to improve the acidification resistance, and eventually the productivity of the energy. In a batch fermentation device, the ability of electrochemical anaerobic digestion (EAD) to resist acidification was evaluated in current intensity, electrode potential, AC impedance, microbial community, pH value, and volatile fatty acids (VFAs). The results showed that the average concentration of VFAs in EAD was 32.9% lower than that in AD, the energy efficiency of EAD is 53.25% higher than AD, indicating that EAD has stronger anti-acidification ability and energy conversion efficiency than AD. When the EAD reaches a steady state, the current intensity fluctuates in the range of 7-12 mA, the electrode potential difference is maintained at 600 ± 5 mV, and the internal resistance decreases from 3333.3 ± 16Ω at startup to 68.9 ± 1.4Ω at the steady state, indicating that the EAD has stronger resistance to acidification may be due to the degradation of some VFAs on the electrode surface. Furthermore, the 16S rRNA sequencing analysis showed that the dominant electricity-producing bacteria on EAD anode surface were Clostridium, Hydrogenophaga and Trichloromonas, with a relative abundance of 40.32%, while the relative abundance of electrogenic bacteria in AD bulk solution and EAD bulk solution were about 1/2 and 1/4 that of EAD anode film, suggesting that the electricity-producing bacteria on the electrode surface play an important role in the degradation of VFAs.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

A system dynamic model for simulating the potential of prefabrication on construction waste reduction.

Prefabrication is a promising method for minimizing construction waste since it is conducted in a controlled environment. This paper develops a simulation model for quantitatively evaluating the potential of prefabrication on construction waste reduction by considering interaction behaviors among factors influencing the application of prefabrication and construction waste reduction during the design stage. The theory of planned behavior is applied to determine the system boundary, and a system dynamic model is applied for establishing the simulation model. A case project in Anhui, China, is selected for demonstrating the established model. Results show that the (1) Application of prefabrication method contributes to construction waste reduction by reducing material wastes and reworking due to design changes. (2) Impacts of prefabrication method on concrete waste reduction is the most significant. (3) Increasing investment on designers' professional training and strengthening policies is two efficient strategies to make full use of the potential of the prefabrication method on construction waste reduction during the design stage. The developed model can offer designers as well as policymakers with references for applying prefabrication method for construction waste reduction by comparing outcomes under various scenarios with different strategies and policies ahead of implementation.

Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with the tumorigenesis of gastric cancer. The aim of the present study was to identify the key regulator in H. pylori-related gastric cancer and to study the expression level and clinical value of the indicated key regulator in gastric cancer. METHODS: The GSE6143 dataset was used to identify differentially expressed genes (DEGs) with limma R package, and enrichment analysis was done using the Metascape web-based portal. The protein-protein interaction analysis was done using Search Tool for the Retrieval of Interacting Genes/Proteins. Gastric adenocarcinoma AGS and BGC-823 cells were treated with H. pylori strain 26695 to construct the in vitro H. pylori infection model, and quantitative reverse transcription polymerase chain reaction was used to analyze the mRNA levels of indicated genes. The correlation analysis between two genes in gastric cancer was done by GEPIA. Furthermore, the PTPRC expression by pathological features analysis was conducted in UALCAN, an easy to use, interactive web-portal (http://ualcan.path.uab.edu). The survival analysis for gastric cancer, based on PTPRC expression levels, was done using the Kaplan-Meier plotter. RESULTS: DEGs in gastric mucosa with or without H. pylori infection were identified and enriched in immune-related pathways and cancer pathways. The protein-protein interaction analysis confirmed the enrichment analysis of gene ontology. H. pylori strain 26695 exposure also confirmed the alteration of gene expression levels in AGS and BGC-823 cells. PTPRC was co-expressed with CSF2RB and TNFRSF7, indicating a significant positive correlation in gastric cancer. PTPRC was overexpressed in gastric cancer, and the overexpression of PTPRC was positively correlated with the progression of gastric cancer. Furthermore, the high expression of PTPRC could act as a poor prognostic factor for gastric cancer patients, especially for those at advanced stage. CONCLUSIONS: H. pylori-induced PTPRC is overexpressed in gastric cancer, and the overexpression of PTPRC is positively associated with the development of gastric cancer. The high expression of PTPRC could serve as poor prognostic biomarker for gastric cancer patients, especially for those at advanced stage. H. pylori-induced PTPRC is a prognostic biomarker for gastric cancer.

Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma.

Retinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

lncRNA PCAT14 Is a Diagnostic Marker for Prostate Cancer and Is Associated with Immune Cell Infiltration.

OBJECTIVE: To investigate the relationship between the long noncoding RNA (lncRNA) Prostate cancer-associated transcription factors 14 (PCAT14) and the clinical characteristics of prostate cancer and immune cell infiltration. METHODS: The relationship between PCAT14 expression and the clinicopathological characteristics of prostate cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC) curves were used to evaluate the value of PCAT14 as a diagnostic marker for prostate cancer. The relationship between PCAT14 and immune cell infiltration was analyzed to explore the effect of PCAT14 on the immune-related functions of prostate cancer. RESULTS: The ROC curve showed that PCAT14 had a significant diagnostic ability (area under curve = 0.818) for prostate cancer. A reduced expression of PCAT14 in prostate cancer was related to T stage, N stage, primary therapy outcome, residual tumor, Gleason score, and age. The expression of PCAT14 was independently associated with the progression-free interval in prostate cancer patients. The infiltration of immune cells in prostate cancer showed a significant negative correlation between the expression of PCAT14 and plasmacytoid dendritic cells, activated dendritic cells, regulatory T cells, and neutrophils. CONCLUSIONS: PCAT14 is highly expressed in prostate cancer and is expected to be a diagnostic marker. PCAT14 might promote the development of prostate cancer through chemokines, antimicrobials, and cytokines that affect the infiltration of immune cells.

MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1.

MicroRNAs (miRNAs) are dysregulated in many tumors and have been found to play crucial roles in cancer biology. Retinoblastoma is a rare tumor that develops rapidly from a malignant tumor of immature cells in the retina known as photoreceptor progenitors. Our study aimed to explore the role of miR-146a in the pathology of retinoblastoma. Potential target gene of miR-146a was predicted by Targetscan. Reverse transcription quantitative polymerase chain reaction (RT-PCR) showed that miR-146a was downregulated and ventral nerve tumor antigen 1 (Neuro - oncological ventral antigen 1, NOVA1) was upregulated in retinoblastoma. Luciferase assay confirmed that miR-146a directly target NOVA1. MiR-146a knockdown and overexpression experiments were performed and found that miR-146a could regulate the expression of NOVA1. The miR-146a knockdown and overexpression experiments were conducted to investigate the biological function of miR-146a. MiR-146a was found inhibited the viability, proliferation and invasion of retinoblastoma cell by MTT, EdU, and transwell assays. Flow cytometry was performed for the apoptosis analysis and miR-146a increased the apoptosis of retinoblastoma cell was found. Above phenomenon can be rescued by overexpression of NOVA1. In conclusion, these results suggest that miR-146a acts as a tumor suppressor and can act as a potential therapeutic target for retinoblastoma in the future.

MSK1 promotes cell proliferation and metastasis in uveal melanoma by phosphorylating CREB.

INTRODUCTION: Uveal melanoma is known as a frequent intraocular tumor, with high metastasis and poor prognosis. Mitogen- and stress-activated protein kinase 1 (MSK1) is a serine/threonine kinase that has been reported to be associated with tumor progression in several types of human cancer. However, the role of MSK1 has rarely been studied in uveal melanoma and the underlying mechanism remained unclear. MATERIAL AND METHODS: The expression level of MSK1 in human uveal melanoma tissues and normal uveal tissues was determined by qRT-PCR analysis, western blotting and immunohistochemistry (IHC). Subsequently, MTT assay, colony formation assay and flow cytometry assay were performed to assess the effects of MSK1 on cell proliferation. Wound-healing and transwell chamber assays were adopted to clarify the role of MSK1 in cell metastasis. Finally, the function of MSK1 was confirmed in vivo in a tumor-bearing mouse model. RESULTS: The expression levels of MSK1 and p-cyclic AMP-responsive element binding protein (CREB) were strongly up-regulated in human uveal melanoma tissues. MSK1 overexpression facilitated cell viability and clone formation, and promoted migration and invasion of uveal melanoma cells. However, mutation of cyclic AMP-responsive element binding protein (CREB) at Ser133 residues reversed the effect of MSK1 on uveal melanoma cell proliferation and metastasis. The in vivo experiment suggested that the tumor weight was lower and the tumor mass grew more slowly in the shMSK1 group as compared to the shNC group. CONCLUSIONS: MSK1 promotes proliferation and metastasis of uveal melanoma cells by phosphorylated CREB at Ser133 residues. Therefore, MSK1 could be a promising candidate for uveal melanoma therapy and especially has tremendous potential in the treatment of cancers in which the MSK1-CREB pathway is abnormally active.

miR-133a-3p promotes apoptosis and induces cell cycle arrest by targeting CREB1 in retinoblastoma.

INTRODUCTION: Retinoblastoma (RB) is a malignant tumor that is derived from photoreceptors. It is common in children under 3 years old with a family genetic predisposition. MicroRNA-133a-3p (miR-133a-3p) is one of the tumor-related miRNAs that interprets a critical function in the genesis and development of various tumors. This study investigated the effects and underlying mechanisms of miR-133a-3p in RB. MATERIAL AND METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was used to assess the miR-133a-3p expression in RB tissues and a cell model. MTT assay, western blot, flow cytometry and luciferase reporter assay were performed to evaluate the effect of miR-133a-3p on cell viability, apoptosis and the cell cycle. An RB xenograft model was established to assess the in vivo influence of miR-133a-3p on RB growth. RESULTS: MiR-133a-3p level was reduced in RB tissues and the cell model (p < 0.01 or p < 0.001). Addition of miR-133a-3p reduced cell viability, and increased apoptosis and cell cycle arrest (p < 0.001). Additionally, CREB1 was identified to be the target of miR-133a-3p in RB cell lines (p < 0.001). Cell viability reduction, apoptosis and cell cycle arrest increases mediated by miR-133a-3p were attenuated by CREB1 overexpression (p < 0.001). MiR-133a-3p inhibited tumor growth of RB in vivo (p < 0.001). CONCLUSIONS: Our results reveal that miR-133a-3p exhibits anti-cancer effects by targeting CREB1 in RB. This study provides a new direction for effective targeted treatment of this disease.