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Jiacheng Wu,1,2,* Haifei Xu,1,* Hao Ji,1 Baoqian Zhai,2 Jinfeng Zhu,1 Mingde Gao,3 Haixia Zhu,2 Xiaolin Wang1 1Department of Urology, Tumor Hospital Affiliated to Nantong University, Nantong University, Nantong 226361, People’s Republic of China; 2Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong University, Nantong 226361, People’s Republic of China; 3Department of Urology, Medical College of Nantong University, Nantong 226019, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixia ZhuCancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong University, No. 30 Tongyang Bei Road, Tongzhou District, Nantong 226361, People’s Republic of ChinaTel +86 138 6290 6771Fax +86 513 8671 2287Email zhx19891027@163.comXiaolin WangDepartment of Urology, Tumor Hospital Affiliated to Nantong University, Nantong University, No. 30 Tongyang Bei Road, Tongzhou District, Nantong 226361, People’s Republic of ChinaTel +86 159 5086 8500Fax +86 513 8672 9043Email cxhwyc2010@163.comObjective: To investigate the association between KRT17 and the prognosis in bladder cancer patients.Methods: The clinical data of 101 patients with bladder cancer from May 2013 to May 2015 were retrospectively analyzed. At the same time, the expression of KRT17 and its correlation with clinicopathological factors were examined by immunohistochemistry. We search the prognostic value of KRT17 in bladder cancer from the cancer genome map (TCGA) online database. To explore the possible cellular mechanism, gene set enrichment analysis (GSEA) was used. The patients were divided into two groups: high expression of KRT17 and low expression of KRT17. The patients were followed up for 5 years to observe the survival. Kaplan–Meier method and Log rank test were used for univariate survival analysis, and Cox regression analysis was used for multivariate analysis. Finally, a nomogram was constructed on this basis for internal verification.Results: Among the 101 patients, 46 (45.5%) were in the KRT17 low expression group and 55 (54.5%) in the high KRT17 expression group. After 5 years of follow-up, 79 patients survived with a survival rate of 78.2% and 22 patients died with a mortality rate of 21.8%. Kaplan–Meier survival analysis showed that OS and PFS of patients with high expression of KRT17 were significantly higher than those of patients with low expression of KRT17 (p< 0.001, p=0.005). Cox multivariate analysis showed that KRT17 expression was an independent risk factor for tumor progression (p=0.019). And tumor size, vascular tumor thrombus, and T stage also affected tumor progression (p< 0.05). In the internal validation, the c-index of nomogram was 0.898 (95% CI: 0.854– 0.941).Conclusion: The decreased expression of KRT17 is associated with poor prognosis in patients with bladder cancer. KRT17 can be used as a novel predictive biomarker to provide a new therapeutic target for bladder cancer patients.Keywords: keratin17, bladder cancer, overall survival, prognosis, progression-free survival, risk factors, nomograph

High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.

Background Evidence indicates that preoperative fibrinogen/prealbumin (FPR), neutrophil lymphocyte ratio/prealbumin ratio (NLR/PA) and platelet distribution width-to-platelet count ratio (PDW/PLT) possess prognostic potential in numerous malignancies. However, their roles in bladder cancer remain unclear. In this study, we investigated the association between FPR, NLR/PA versus PDW/PLT and the prognosis in bladder cancer patients. Methods The clinical data of 147 patients with bladder cancer treated in Nantong cancer hospital from January 2009 to August 2014 were retrospectively analyzed. According to ROC curve, the optimal critical value of FPR, NLR/PA and PDW/PLT were 0.1084, 0.1045 and 0.1210 respectively. The patients were followed up for 5 years to observe the survival of the patients, and the clinicopathological data were statistically analyzed. Cox regression analysis was used for univariate and multivariate analysis. Finally, on this basis, the nomogram is constructed for internal verification. Results All patients were followed up for 5 years. A total of 102 patients survived with a survival rate of 69.4%, 45 patients died with a mortality rate of 30.6%. Further stratified analysis showed that the group with low FPR, low NLR/PA and low PDW/PLT had the best prognosis, while the group with high FPR, high NLR/PA and high PDW/PLT had the worst prognosis. Cox multivariate analysis showed that preoperative FPR, NLR/PA and PDW/PLT were independent risk factors for tumor progression (p = 0.007, p = 0.013, p = 0.000). The decrease of FPR, NLR/PA and PDW/PLT can significantly prolong OS and PFS in patients with bladder cancer. In internal validation, the c-index of the nomogram was 0.8140 (95% CI: 0.7577–0.8703). Conclusions Preoperative FPR and NLR/PA versus PDW/PLT can be an independent prognostic factor in bladder cancer patients and are associated with clinicopathological characteristics. They have a specific value in assessing the prognosis of bladder cancer patients.

In dredging project, the $\gamma$ -ray based source densitometer is widely used to measure the concentration in solid-liquid two-phase flow, whereas it is radiant, polluted, and inaccurate. Recently, electric densitometers based on Electric Impedance Tomography(EIT) technology has developed to replace the $\gamma$ -ray source densitometer. However, the calibration and velocity of electrical densitometer is very difficult since complex working conditions cannot be uniformly tested and reconstructed. In this paper, a simple and effective device is designed to calibrate the results of the electrical densitometer. Experiments show that the device can reconstruct typical working conditions in dredging projects and accomplish quantitative analysis.

The deposition of Schistosoma japonicum (S. japonicum) eggs commonly induces inflammation, fibrosis, hyperplasia, ulceration, and polyposis in the colon, which poses a serious threat to human health. However, the underlying mechanism is largely neglected. Recently, the disorder of glucose and lipid metabolism was reported to participate in the liver fibrosis induced by the parasite, which provides a novel clue for studying the underlying mechanism of the intestinal pathology of the disease. This study focused on the metabolic reprogramming profiles of glucose and lipid in the colon of mice infected by S. japonicum. We found that S. japonicum infection shortened the colonic length, impaired intestinal integrity, induced egg-granuloma formation, and increased colonic inflammation. The expression of key enzymes involved in the pathways regulating glucose and lipid metabolism was upregulated in the colon of infected mice. Conversely, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and its downstream signaling targets were significantly inhibited after infection. In line with these results, in vitro stimulation with soluble egg antigens (SEA) downregulated the expression of PTEN in CT-26 cells and induced metabolic alterations similar to that observed under in vivo results. Moreover, PTEN over-expression prevented the reprogramming of glucose and lipid metabolism induced by SEA in CT-26 cells. Overall, the present study showed that S. japonicum infection induces the reprogramming of glucose and lipid metabolism in the colon of mice, and PTEN may play a vital role in mediating this metabolic reprogramming. These findings provide a novel insight into the pathogenicity of S. japonicum in hosts.

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC. Compelling evidence has highlighted the crucial role of long non-coding RNA (lncRNA) in ccRCC. Our current study aims to explore the regulatory mechanism of LINC01094 in the development of ccRCC. Dual-luciferase reporter experiment verified the targeting relationship among miR-184, LINC01094, and SLC2A3. Furthermore, the interaction between LINC01094 and miR-184 was confirmed by RNA immunoprecipitation (RIP) and RNA pull-down. Biological behaviors of ccRCC cells were investigated through cell counting kit-8 (CCK8), scratch test, Transwell, and flow cytometry. The effect of SLC2A3 on the tumorigenicity of nude mice was evaluated in vivo. In ccRCC cells and clinical tissues, LINC01094 and SLC2A3 were highly expressed while miR-184 was lowly expressed. Besides, miR-184 was verified to be a direct target of LINC01094. Silencing LINC01094, up-regulating miR-184, or reducing SLC2A3 inhibited the growth, migration, and invasion of ccRCC cells. Tumor growth was suppressed by silenced LINC01215 via reducing the expression of SLC2A3 via miR-184. Taken together, silencing LINC01094 inhibited SLC2A3 expression by up-regulating miR-184, thereby inhibiting the development of ccRCC.

Pancreatic cancer is one of the most malignant tumors worldwide, and pancreatic ductal adenocarcinoma is the most common type. In pancreatic cancer, glycolysis is the primary way energy is produced to maintain the proliferation, invasion, migration, and metastasis of cancer cells, even under normoxia. However, the potential molecular mechanism is still unknown. From this perspective, this review mainly aimed to summarize the current reasonable interpretation of aerobic glycolysis in pancreatic cancer and some of the newest methods for the detection and treatment of pancreatic cancer. More specifically, we reported some biochemical parameters, such as newly developed enzymes and transporters, and further explored their potential as diagnostic biomarkers and therapeutic targets.

Background Preoperative platelet distribution width-to-platelet count ratio (PDW/PLT) has been discussed about its prognostic value in several malignancies, whereas its role in bladder cancer remains unclear. In this study, we attempt to investigate the relationship between the PDW/PLT and the prognosis of patients with bladder cancer.Patients and Methods The clinical data of 115 cases of bladder cancer treated in urology department of Nantong tumor hospital from January 2009 to August 2014 were analyzed retrospectively. The best critical value of PDW/PLT was 0.09965 determined by ROC curve. The patients were divided into low PDW/PLT group and high PDW/PLT group. After 5 years of follow-up, survival was observed, and the clinicopathological data of patients were statistically analyzed. Kaplan Meier method and log rank test were used for single factor survival analysis, and Cox regression analysis was used for multiple factors survival analysis.Results The age of patients in low PDW/PLT group was significantly lower than that in high PDW/PLT group (P=0.008). There was no significant difference between the two groups in gender, TNM stage, grade, lymph node metastasis, distant metastasis, operation method, history of hypertension, history of diabetes, and other operation history (P>0.05). All patients were followed up for 5 years. 89 patients survived, the survival rate was 77.4%, 26 patients died, the mortality rate was 22.6%. There were 94 cases (81.7%) in low PDW/PLT group and 21 cases (18.3%) in high PDW/PLT group. The tumor progression rates of low PDW/PLT group and high PDW/PLT group were 57.4% (54/94) and 71.4% (15/21) respectively. The median PFS was 85 months and 71 months respectively. There was no significant difference between the two groups (P>0.05). Single factor analysis showed that TNM stage, grade, lymph node metastasis, PDW/PLT were the factors affecting OS (P

Background Hepatocellular carcinoma(HCC) is the sixth most common cancer worldwide, and is associated with a high mortality rate and poor treatment efficacy. Therefore, it is important to explore the underlying mechanisms and screen for novel biomarkers and therapeutic targets. Methods HCC and non-tumor microarray data was obtained from the Gene Expression Omnibus(GEO) database and 1,612 differentially expressed genes (DEGs) were identified. The identified DEGs were then further examined using a weighted gene co-expression network analysis (WGCNA). Modules were identified and correlations with clinical parameters were examined to ultimately identify a single highly correlated module containing a single hub gene, phosphoenolpyruvate carboxykinase 2 (PCK2).The genes co-expressed with PCK2 were then examined via Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and were found to be primarily enriched in the area of energy metabolism. The association between PCK2 expression and prognosis and tumor stage was then further verified by using a HCC dataset obtained from The Cancer Genome Atlas (TCGA) database. Ex vivo examination of HCC and adjacent non-tumor samples via quantitative real-time PCR demonstrated that PCK2 is downregulated in HCC. Additionally, HCC cell lines overexpressing PCK2 exhibited a time-dependent reduction in cellular viability. Results These findings demonstrate that PCK2 is downregulated in HCC and is associated with HCC prognosis and tumorstage, and that PCK2 may affect HCC progression via energy metabolism. Conclusions this study may help to further elucidate possible HCC progression mechanisms and the findings presented here suggest that PCK2 may serve as a potential HCC therapeutic target or biomarker.

Introduction: Postoperative pancreatic fistula is the most troublesome complication after pancreaticoduodenectomy, and is an on-going area of concern for pancreatic surgeons. The specific pancreati...

It has very important application value to investigate the damage mechanism of CaF2 windows irradiated by ultraviolet excimer laser. As significant optical materials, CaF2 windows have been widely used in the ultraviolet photoelectrical field. Because the ultraviolet excimer laser presents favorable characteristics such as short wavelength and high photon energy, the high power excimer lasers are expected to be widely applied in precision laser machining and military field. In this paper, the experiment on damage in CaF2 windows irradiated by 248nm ultraviolet excimer laser was carried out. The damage characteristics of irradiated spots under different experiment conditions were detected by optical microscope. The laser induced damage thresholds of CaF2 windows were calculated by the zero damage probability through linear fitting. The damage mechanism of CaF2 windows were discussed based on the surface characteristics of damage spots. The experimental results indicated that the damage thresholds of zero probability for the 248nm excimer laser to CaF2 windows were 5.6J/cm2 of the incident surface, and 1.1J/cm2 of the exit surface respectively. When CaF2 windows was irradiated by 248nm excimer laser, its damage first occurred to its exit surface, the damage threshold of exit surface was smaller than that of incident surface. As the laser fluence increased gradually, the damage of exit surface was shown to grow exponential and its degree was significantly higher than that of incident surface. This work is helpful to further improve damage resistance of CaF2 windows in high power laser facility. It can provide the necessary references for selection of ultraviolet optical materials and optimization of application.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

Fertility and endocrine function rely on a tightly regulated synchronicity within the hypothalamic-pituitary gonadal (HPG) axis. FSH/cAMP/MAPK/ Sox9 axis signaling and its regulated specific miRNAs are thought to regulate vertebrate gonadal development and sex differentiation, and yet the regulatory networks are largely unknown. Here we construct small RNA and mRNA libraries from sexually matured ovary and testis of zebrafish to identify specific miRNA-target pairs. Integration of Targetscan prediction and in vivo induced gene expression highlight four specific miRNAs that conditionally target three G protein–coupled receptor (GPCR) x-Sox9 signaling genes, and implicate two regulatory circuits of miR430a-Sox9a in the testis and miR218a-Sox9b in the ovary. Co-injected Sox9a-miR430a mixture increases the proportion of spermatogonia but degenerates primary oocyte, while Sox9b-miR218a mixture induces renewal of ovarian follicles. Co-immunoprecipitation and mass-spectrometry analyses further reveal that miR430a and Sox9a synergistically activate testicular PKC/Rock1 signals while miR218a and Sox9b constrict ovary PKC/PI3K/Rock1 signaling. These results clarify specific miRNAs-GPCR regulatory networks of Sox9a/Sox9b switch, and also provide mechanistic insight into gonadal rejuvenation and plasticity.

As a critical step during innate response, the cytoplasmic β subunit (IFN-γR2) of interferon-γ receptor (IFN-γR) is induced and translocates to plasma membrane to join α subunit to form functional IFN-γR to mediate IFN-γ signaling. However, the mechanism driving membrane translocation and its significance remain largely unknown. We found, unexpectedly, that mice deficient in E-selectin, an endothelial cell-specific adhesion molecule, displayed impaired innate activation of macrophages upon Listeria monocytogenes infection yet had increased circulating IFN-γ. Inflammatory macrophages from E-selectin-deficient mice had less surface IFN-γR2 and impaired IFN-γ signaling. BTK elicited by extrinsic E-selectin engagement phosphorylates cytoplasmic IFN-γR2, facilitating EFhd2 binding and promoting IFN-γR2 trafficking from Golgi to cell membrane. Our findings demonstrate that membrane translocation of cytoplasmic IFN-γR2 is required to activate macrophage innate response against intracellular bacterial infection, identifying the assembly of functional cytokine receptors on cell membrane as an important layer in innate activation and cytokine signaling.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, accounting for 90% of primary liver cancers, and its incidence is still increasing. While the curative treatment for HCC is surgical resection and liver transplantation, most patients are in advanced stage, and lose the chance of surgery. Other palliative treatments include radiofrequency ablation, transarterial embolization, chemotherapy, and radiotherapy. Although there are so many treatments, the prognosis of HCC is still very poor. A major obstacle for the treatment for HCC is the high frequency of tumor recurrence even after curative resection and liver transplantation. Since HCC is frequently resistant to conventional chemotherapy and radiotherapy, clinical development of novel therapeutic agents against HCC has begun in earnest. Thus far, a series of adjuvant therapies for HCC have emerged, including small molecular target agents, monocolonal antibodies, microRNA, and Chinese herbal medicine. Some agents such as sorafenib have shown an advantage in prolonging the overall survival time, and has been approved by FDA for the treatment of advanced HCC. In this article we review the current situation and prospects of adjuvant therapies for HCC.