The Association between Circulating Lipids and Female Infertility Risk: A Univariable and Multivariable Mendelian Randomization Analysis.

BACKGROUND: Although observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blood lipids and female infertility. METHODS: Single-nucleotide polymorphisms associated with lipid traits in univariate analysis were obtained from the Million Veteran Program (MVP) and Global Lipids Genetics Consortium (GLGC), involving up to 215,551 and 188,577 European individuals, respectively. Blood lipids in multivariate analysis were obtained from the latest genome-wide association study meta-analysis with lipid levels in 73 studies encompassing >300,000 participants. Data on female infertility were obtained from the FinnGen Consortium R6 release, which included 6481 samples and 75,450 controls. Subsequently, MR analysis was performed using inverse variance-weighted (IVW), weighted median, weighted-mode, simple-mode and MR-Egger regression to demonstrate the causal relationship between lipids and female infertility. RESULTS: After controlling confounding factors including body mass index and age at menarche, two-sample MR demonstrated that genetically predicted LDL-C and TC were causally associated with the risk of female infertility (When the genetic instruments come from the MVP database, LDL-C and female infertility, IVW OR: 1.13, 95% CI: 1.001-1.269, p = 0.047; TC and female infertility, IVW OR: 1.16, 95% CI: 1.018-1.317, p = 0.025, and when the genetic instruments came from the GLGC database, LDL-C and female infertility, IVW OR: 1.10, 95% CI: 1.008-1.210, p = 0.033; TC and female infertility, IVW OR: 1.14, 95% CI: 1.024-1.258, p = 0.015). However, the IVW estimate showed that HDL-C was not significantly associated with the risk of female infertility (when the genetic instruments came from the MVP database, IVW OR: 1.00, 95% CI: 0.887-1.128, p = 0.999; when the genetic instruments came from the GLGC database, IVW OR: 1.00, 95% CI: 0.896-1.111, p = 0.968). The multivariable MR analysis also provided evidence that LDL-C (OR: 1.12, 95% CI: 1.006-1.243, p = 0.042) was significantly associated with the risk of female infertility after considering the correlation of all lipid-related traits. CONCLUSION: These findings support a causal relationship between increased LDL-cholesterol and increased female infertility risk. Furthermore, the association between lipid-related traits and female infertility risk merits more studies.

EXOSC8 promotes colorectal cancer tumorigenesis via regulating ribosome biogenesis-related processes.

Extensive protein synthesis is necessary for uncontrolled cancer cell proliferation, requiring hyperactive ribosome biogenesis. Our previous Pan-cancer study has identified EXOSC8 as a potential copy number variation (CNV)-driven rRNA metabolism-related oncogene in colorectal cancer (CRC). Herein, we further investigated proliferation-prompting functions and mechanisms of EXOSC8 in CRC by performing in silico analyses and wet-lab experiments. We uncovered that increased EXOSC8 expression and CNV levels are strongly associated with ribosome biogenesis-related factor levels in CRC, including ribosome proteins (RPs), eukaryotic translation initiation factors and RNA polymerase I/III. EXOSC8 silence decreases nucleolar protein and proliferation marker levels, as well as rRNA/DNA and global protein syntheses. Clinically, EXOSC8 is upregulated across human cancers, particularly CNV-driven upregulation in CRC was markedly associated with poor clinical outcomes. Mechanistically, EXOSC8 knockdown increased p53 levels in CRC, and the oncogenic proliferation phenotypes of EXOSC8 depended on p53 in vitro and in vivo. We discovered that EXOSC8 knockdown in CRC cells triggers ribosomal stress, nucleolar RPL5/11 being released into the nucleoplasm and "hijacking" Mdm2 to block its E3 ubiquitin ligase function, thus releasing and activating p53. Furthermore, our therapeutic experiments provided initial evidence that EXOSC8 might serve as a potential therapeutic target in CRC. Our findings revealed, for the first time, that the RNA exosome gene (EXOSC8) promotes CRC tumorigenesis by regulating cancer-related ribosome biogenesis in CRC. This study further extends our previous Pan-cancer study of the rRNA metabolism-related genes. The inhibition of EXOSC8 is a novel therapeutic strategy for the RPs-Mdm2-p53 ribosome biogenesis surveillance pathway in CRC.

Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. METHODS: The expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments. RESULTS: We discovered that DLGAP1-AS2 promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21 (Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2 decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3). CONCLUSIONS: The discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease.

Long-Life Lithium-Metal All-Solid-State Batteries and Stable Li Plating Enabled by In Situ Formation of Li3 PS4 in the SEI Layer.

An ultrastable and kinetically favorable interface is constructed between sulfide-poly(ethylene oxide) (PEO) composite solid electrolytes (CSEs) and lithium metal, via in situ formation of a solid electrolyte interphase (SEI) layer containing Li3 PS4 . A specially designed sulfide, lithium polysulfidophosphate (LPS), can distribute uniformly in the PEO matrix via a simple stirring process because of its complete solubility in acetonitrile solvent, which is advantageous for creating a homogeneous SEI layer. The CSE/Li interface with high Li+ transportation capability is stabilized quickly through in situ formation of a Li3 PS4 /Li2 S/LiF layer via the reaction between LPS and lithium metal to inhibit lithium dendrite growth. A Li/Li symmetric cell with the LPS-integrated CSE exhibits constant and small CSE/Li resistance of 10 Ω cm2  during cycling, delivering stable cycling for 3475 h at a current density of 0.2 mA cm-2  and a high critical current density of 0.9 mA cm-2  at 60 °C. Impressive electrochemical performance is also demonstrated for LiFePO4 /CSE/Li all-solid-state batteries with capacity of 127.6 mAh g-1  after 1000 cycles at 1 C.

Nanobody-Engineered Natural Killer Cell Conjugates for Solid Tumor Adoptive Immunotherapy.

Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK cells are deficient in ligands that target specific tumors, resulting in limited antitumor efficacy. Here, a glycoengineering approach to imitate the chimeric antigen receptor strategy and decorate NK cells with nanobodies to promote NK-based immunotherapy in solid tumors is proposed. Nanobody 7D12, which specifically recognizes the human epidermal growth factor receptor (EGFR) that is overexpressed on many solid tumors, is coupled to the chemically synthesized DBCO-PEG4 -GGG-NH2 by sortase A-mediated ligation to generate DBCO-7D12. The NK92MI cells bearing azide groups are then equipped with DBCO-7D12 via bioorthogonal click chemistry. The resultant 7D12-NK92MI cells exhibit high specificity and affinity for EGFR-overexpressing tumor cells in vitro and in vivo by the 7D12-EGFR interaction, causing increased cytokine secretion to more effectively kill EGFR-positive tumor cells, but not EGFR-negative cancer cells. Importantly, the 7D12-NK92MI cells also show a wide anticancer spectrum and extensive tumor penetration. Furthermore, mouse experiments reveal that 7D12-NK92MI treatment achieves excellent therapeutic efficacy and outstanding safety. The authors' works provide a cell modification strategy using specific protein ligands without genetic manipulation and present a potential novel method for cancer-targeted immunotherapy by NK cells.

SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop.

BACKGROUND: Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. METHODS: SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. RESULTS: Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. CONCLUSIONS: We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.

Immune checkpoint molecule TIGIT manipulates T cell dysfunction in septic patients.

Sepsis is a dysregulated host response to infection. T cell dysfunction results in the failure to eradicate pathogens and the increased susceptibility to nosocomial infections and mortality during sepsis. Although PD-1 has shown to be a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Here we demonstrated that the immune checkpoint molecule TIGIT on lymphocytes and the critical role of TIGIT in regulating T cell responses in sepsis. Fifty septic patients and seventeen healthy donors were prospectively enrolled. The expression patterns of TIGIT and other molecules on lymphocytes were quantitated by flow cytometry. Ex vivo functional assays were also conducted. Results show that TIGIT expression on T cells was significantly upregulated in sepsis and septic shock patients relative to healthy donors. Elevated frequencies of TIGIT+ T cells correlated with aggravated inflammatory response and organ injuries. Of note, TIGIT expression on CD8+ T cells showed a competitive capability to predict ICU mortality in sepsis. TIGIT+ T cells expressed higher levels of PD-1, lower levels of CD226, and released fewer cytokines. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells from septic patients. These data illustrate that TIGIT on T cells is being used not only as a clinical predictor of poor prognosis but also as a potential target of novel immunotherapeutic intervention during sepsis.

Long noncoding RNA MCM3AP-AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR-193a-5p/SENP1.

BACKGROUND: Accumulating evidences have shown that long noncoding RNAs (lncRNAs) play key roles in many diseases, including cancer. Several studies reported that MCM3AP antisense RNA 1 (MCM3AP-AS1) was associated with the tumorigenesis and progression. However, the specific function and mechanism of MCM3AP-AS1 in colorectal cancer (CRC) have not been fully understood. METHODS: The expression of MCM3AP-AS1 was detected by quantitative reverse transcription PCR (RT-qPCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK-8 assay, colony formation assay, transwell assay, xenograft and lung metastasis mouse models were used to examine the tumor-promoting function of MCM3AP-AS1 in vitro and in vivo. The binding relationship between MCM3AP-AS1, miR-193a-5p and sentrin-specific peptidase 1 (SENP1) were screened and identified by databases, RT-qPCR, dual luciferase reporter assay and western blot. RESULTS: In the present study, we got that the expression of MCM3AP-AS1 was higher in CRC tissues than in paired NCTs, and increased MCM3AP-AS1 expression was associated with adverse outcomes in CRC patients. Functional experiments in vitro revealed that silencing of MCM3AP-AS1 could inhibit the proliferation, colony formation, migratory, and invasive abilities of CRC cells. The mouse models of xenograft and lung metastasis further confirmed that in vivo silencing MCM3AP-AS1 could significantly inhibit the growth and metastasis of CRC. Further mechanism studies indicated that MCM3AP-AS1 could sponge miR-193a-5p and inhibit the activity of it. What is more, SENP1 was proved to be a novel target of miR-193a-5p and could be upregulated by MCM3AP-AS1. At last, we observed that SENP1 overexpression in CRC tissues was closely related to unfavorable prognosis. CONCLUSION: Taken together, we identified in CRC the MCM3AP-AS1/miR-193a-5p/SENP1 regulatory axis, which affords a therapeutic possibility for CRC.

Ternary flower-sphere-like MnO2-graphite/reduced graphene oxide nanocomposites for supercapacitor.

Chemical fabrication of a nanocomposite structure for electrode materials to regulate the ion diffusion channels and charge transfer resistances and Faradaic active sites is a versatile strategy towards building a high-performance supercapacitor. Here, a new ternary flower-sphere-like nanocomposite MnO2-graphite (MG)/reduced graphene oxide (RGO) was designed using the RGO as a coating for the MG. MnO2-graphite (MnO2-4) was obtained by KMnO4 oxidizing the pretreated graphite in an acidic medium (pH = 4). The GO coating was finally reduced by the NaBH4 to prepare the ternary nanocomposite MG. The microstructures and pore sizes were investigated by x-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and nitrogen adsorption/desorption. The electrochemical properties of MG were systematically investigated by the cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy in Na2SO4 solution. The MG as an electrode material for supercapacitor exhibits a specific capacitance of 478.2 and 454.6 F g-1 at a current density of 1.0 and 10.0 A g-1, respectively. In addition, the capacitance retention was 90% after 8,000 cycles. The ternary nanocomposite enhanced electrochemical performance originates from the specific flower-sphere-like morphology and coating architecture bringing higher specific surface area and lower charge transfer resistance (Rct).

[Ectopic seminal tract opening in enlarged prostatic utricle: A report of 22 cases].

OBJECTIVE: To explore the diagnosis, classification and treatment of ectopic seminal tract opening in enlarged prostatic utricle (EPU). METHODS: We retrospectively analyzed the clinical data on 22 cases of ectopic seminal tract opening in EPU confirmed by spermography, EPU open cannula angiography or intraoperative puncture of the vas deferens and treated by transurethral incision of EPU, cold-knife incision or electric incision of EPU, full drainage of the anteriorwal, and open or laparoscopic surgery from October 1985 to October 2017. RESULTS: Five of the patients were diagnosed with ectopic opening of the vas deferens and the other 17 with ectopic opening of the ejaculatory duct in EPU. During the 3－48 months of postoperative follow-up, symptoms disappeared in all the cases, semen quality was improved in those with infertility, and 2 of the infertile patients achieved pregnancy via ICSI. CONCLUSIONS: Ectopic seminal tract opening in EPU is rare clinically. Spermography is a reliable method for the diagnosis of the disease, and its treatment should be aimed at restoring the smooth flow of semen based on proper classification and typing of the disease.

Sam68 promotes aerobic glycolysis in colorectal cancer by regulating PKM2 alternative splicing.

BACKGROUND: Sam68, an RNA-binding protein, exerts oncogenic functions in several types of cancer. However, the specific functions and mechanisms of Sam68 in colorectal cancer (CRC) had not been previously clarified. Pyruvate kinase muscle (PKM)2 is the key rate-limiting enzyme in glycolysis, and PKM2 maintains the glycolysis-dominant energy metabolism in most cancer cells. METHODS: CCK8 assay was performed to show the effect of Sam68 on cell growth. Pyruvate kinase activity and lactate detection assays were performed to analyze the effects of Sam68 on aerobic glycolysis. RNA immunoprecipitation (RIP) was used to detect the binding of Sam68 to the PKM2 sequence. Western blot and real-time PCR were executed to analyze the regulation of PKM2 by Sam68. RESULTS: Gain-of-function and loss-of-function studies showed that ectopic expression of Sam68 promoted glycolysis and cell proliferation in CRC cells, whereas Sam68 knockdown inhibited glycolysis and cell proliferation. Mechanically, Sam68 modulated the expression profile of pyruvate kinase (PKM2 or PKM1) by regulating its alternative splicing. Overexpression of Sam68 was associated with decreased PKM1/PKM2 ratio, which positively contributed to the glycolysis procedure. Sam68 significantly promoted cell proliferation and caused a decrease of PKM1/PKM2 ratio, resulting in the metabolism of glucose switched from oxidative phosphorylation to glycolysis in CRC cells. Besides, Sam68 enhanced PKM2 mRNA transport from the nucleus to cytoplasm and increased the expression of PKM2 protein, resulting in elevated pyruvate kinase activity and lactate production. CONCLUSIONS: These findings suggested that Sam68 affected cell growth and glycolysis pathway by regulating the alternative splicing and expression of PKM2 in CRC.

Case Report: Prostate Adenocarcinoma With Mucinous Features of Normal-Level Serum PSA, Atypical Imaging, Biopsy-Negative, and Peculiar Urethrocystoscopic Manifestation.

BACKGROUND: Mucinous tumors of the prostate are seen as rare morphological variants of prostate carcinoma. Misdiagnosis and missed diagnosis are frequent clinically, especially when the clinical performance appears atypical. Furthermore, there has not been reported about the urethrocystoscopic performance of mucinous adenocarcinoma growing into the prostatic urethra so far. CASE PRESENTATION: The current case report describes a 48-year old Asian male who was hospitalized because of intermittent gross hematuria for more than two months. The patient was diagnosed as prostatic space occupying lesions and an examination of needle biopsy was conducted on him, which did not indicate a definite malignancy. Transurethral plasma kinetic resection of the prostate (TUPKP) was performed for the patient, but the postoperative pathology revealed prostatic adenocarcinoma with mucinous features. Specifically, two cord-like neoplasms, extending to the bladder neck, were found through urethrocystoscopy in the prostatic urethra, both of which grew pedicles. The pedicles were situated on the right side of the parenchyma of the prostate. Finally, the patient underwent radical prostatectomy three weeks later. CONCLUSION: Here, we reported a case that prostatic adenocarcinoma with mucinous features was diagnosed after TUPKP. The patient had normal serum prostate-specific antigen levels with atypical images and negative biopsy result. This report lays stress on the vigilance of clinicians in prostate mucinous adenocarcinoma and makes a description of its peculiar urethrocystoscopic manifestation, typical imaging, and unique growth pattern for the first time.

[Expression of AXL enhances docetaxel-resistance of prostate cancer cells].

OBJECTIVE: To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms. METHODS: Using Western blot, we examined the expressions of the AXL protein, p-AXL and Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel. We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA, respectively, which were confirmed to be effective, detected the proliferation, apoptosis and cycle distribution of the cells by CCK8, MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel, and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel. RESULTS: The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P <0.05). The expressions AXL and p-AXL were remarkably higher (P <0.05) while that of Gas6 markedly lower (P <0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells. The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P <0.05). MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells, with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P <0.05). R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells, even more significantly in combination with docetaxel than used alone (P <0.05). CONCLUSIONS: The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel, which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.

Role of the functional variant (-652T>G) in the XRCC4 promoter in prostate cancer.

Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (-652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 -652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the -652G allele compared to carriers of the -652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter -652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case-control studies are required to validate our findings in the future.

Preparation and antibacterial property of silver-containing mesoporous 58S bioactive glass.

The modified mesoporous 58S bioglass (SM58S) was prepared through surface modification of the mesoporous 58S bioglass (M58S) with γ-aminopropyl triethoxysilane (KH550). The results of Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) showed that the amino groups were grafted to the surface of M58S after modification with KH550. The silver-containing SM58S (Ag-SM58S) and M58S (Ag-M58S) were prepared by the dipping method. The Ag(+) loading capacity, release rate and antibacterial properties of Ag-SM58S and Ag-M58S were investigated. It is indicated that surface modification of M58S with KH550 can improve the Ag(+) loading capacity. The result of antibacterial property showed that Ag-SM58S exhibited significant anti-bacterial effects against Escherichia coli and Staphylococcus aureus. The sustained release of Ag(+) from Ag-SM58S for 768h ensured excellent antibacterial property of Ag-SM58S. In vitro osteoblast proliferation and differentiation tests showed that Ag-SM58S was a good matrix for the growth of osteoblasts. Consequently, the results of the study suggested that Ag-SM58S might be a promising bone repair material.

A novel integrated biosensor based on co-immobilizing the mediator and microorganism for water biotoxicity assay.

A novel integrated biosensor for biotoxicity assay has been developed by co-immobilizing microorganisms and mediators within a novel redox hydrogel. The proposed redox hydrogel acts as an immobilizing matrix both for microorganism E. coli and redox mediator, which was prepared by grafting the benzoquinone (BQ) redox mediator with gelatin/silica hybrid hydrogel (GSH). This redox hydrogel was characterized by UV-Vis, CV and EIS. The feasibility of the novel integrated biosensor for biotoxicity assay was demonstrated by measuring the heavy metal ions Hg(2+), Cu(2+) and Cd(2+) polluted water as the model toxicants. The results showed that the integrated biosensor was able to evaluate the water biotoxicity and the corresponding 50% inhibiting concentrations (IC50) are determined to be 21.2 µg mL(-1), 44 µg mL(-1) and 79 µg mL(-1), respectively. This integrated biosensor could achieve real-time monitoring of water quality and evaluation of biotoxicity. Moreover it avoids the waste and contamination of mediators, and also simplifies the assay process.

[Composition and morphology of stones in enlarged prostatic utricle].

OBJECTIVE: To investigate the composition and morphology of the stones in the enlarged prostatic utricle (EPU). METHODS: We took out 36 EPU stones from 11 patients by transurethral fenestration between 1992 and 2011, and analyzed the stones by scanning electron microscopy, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIS). RESULTS: Under the scanning electron microscope, all the EPU stones were constituted of many intensive minicrystals and amorphous matrix. XRD and FTIS revealed that all were hydroxyapatite crystal. CONCLUSION: EPU stones belong to the category of prostatic pseudo-calculi, whose formation is ascribed not to the abnormal change of urine composition, but to the continuous secretion, absorption and concentration of EPU liquid and ablated epithelial cells from the EPU.

[TRAIL gene polymorphism and genetic susceptibility to prostate cancer in the Chinese Han population of Nanjing].

OBJECTIVE: To investigate the correlation between the polymorphism of the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and the genetic susceptibility to prostate cancer (PCa) in the Chinese Han population in Nanjing. METHODS: We performed a case control study on 187 cases of PCa and 237 cancer-free healthy controls. Peripheral blood genome DNA was extracted from the subjects for analysis of the polymorphism of the TRAIL-716 locus by polymerase chain reaction-ligase detection reaction (PCR-LDR). The correlations between the susceptibility to PCa and different genotypes were compared. RESULTS: An SNP (-716A/G) was found in the promoter of the TRAIL gene. AA, AG and GG genotypes were identified. Logistic regression analysis suggested that AG, GG and AG + GG genotypes had no significant correlation with the risk of PCa (OR = 0.89, 95% CI = 0.54 -1.47; OR = 0.94, 95% CI = 0.69 -1.27; OR = 0.87, 95% CI = 0.54 - 1.41). CONCLUSION: The TRAIL-716 polymorphism is not directly related with the genetic susceptibility to PCa in the Chinese Han population of Nanjing.

VEGFA +936C>T polymorphism and cancer risk: a meta-analysis.

Vascular endothelial growth factor A (VEGF-A), a major driver of physiological and pathological angiogenesis, plays important roles in the etiology and metastasis of cancers. The +936C>T polymorphism in the 3'-untranslated region of the VEGFA gene has been implicated in cancer risk and is related to VEGF-A protein production; however, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed of 13,293 cancer cases and 12,308 control subjects from 29 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between +936C>T polymorphism and cancer risk. The meta-analysis indicated that individuals with the +936 T had increased risk of oral cancer (OR = 1.39, 95% CI = 1.03-1.88), although no association was found in the contrast of T versus C (OR = 1.00, 95% CI = 0.91-1.10) in the pooled analyses. This meta-analysis supports the idea that VEGFA + 936 T is associated with increased risk of oral cancer. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between VEGFA + 936C>T polymorphism and cancer risk.