[Diffusive Fluxes and Controls of N2O from Coastal Rivers in Tianjin City].

Rivers are an important emission source of greenhouse gases. To explore the spatial characteristics and influencing factors of N2O emission from the coastal rivers in Tianjin City, six rivers into the Bohai Sea from different land-use types were selected, and the N2O concentrations, saturation, and diffusive fluxes were measured using the headspace-gas chromatography method. The N2O concentration was in supersaturation, and the rivers were the source of atmospheric N2O. The average concentration, saturation, and diffusive fluxes of N2O were (23.85±15.20) nmol·L-1, (309.71±197.38)%, and (27.04±16.46) µmol·(m2·d)-1, with the ranges of 12.70-115.69 nmol·L-1, 164%-1502%, and 9.17-244.79 µmol·(m2·d)-1, respectively. The N2O concentrations and diffusive fluxes of the rivers presented great spatial heterogeneity, with the sewage river (Huangdipai River)>urban river (Haihe River main stream, Jiyun River)>suburban river (Duliujian River, Yongding Xinhe River)>agricultural river (Chaobai Xinhe River). The N2O concentration and diffusion fluxes were significantly correlated with salinity, nutrients, and carbon sources. NO3--N and TP contributed greatly to the diffusive flux differences. N2O production and emission greatly related to the nitrogen cycle process in the Tianjin River, and different forms of nitrogen variously contributed to N2O diffusive fluxes. The salinity gradient had the opposite effect on the N2O emission in urban rivers and drainage rivers. The N2O diffusive fluxes of the sewage river in Tianjin were significantly higher than that of other river types. In the future, due to the development of urbanization and the expansion of urban land, more management measures should focus on the hotspots such as the downstream of wastewater treatment plants of sewage rivers, the estuaries of urban rivers, and the residential gathering areas of suburban rivers to reduce N2O emission.

Overexpression of phosphatidylethanolamine-binding protein 4 (PEBP4) associates with recurrence of meningiomas.

BACKGROUND AND PURPOSE: Abnormal expression of phosphatidylethanolamine-binding protein 4 (PEBP4) has been identified in various types of malignant tumors. In the present study, we investigated the expression of PEBP4 in meningioma cases and examined whether PEBP4 expression was correlated with outcomes among these patients. MATERIALS AND METHODS: The expression levels of PEBP4 and Ki-67 in human meningioma tissues from 65 patients were evaluated by immunohistochemical staining. The correlation between PEBP4 immunoreactivity in meningioma samples and patients' clinical outcomes was examined using the Kruskal-Wallis correlation test. The prognostic value of PEBP4 expression in meningiomas patients also was investigated. RESULTS: Immunohistochemical analysis revealed up-regulated PEBP4 expression in both atypical and anaplastic meningiomas compared with classical meningiomas (13.38 ± 4.19% vs. 3.64 ± 2.04%, P < 0.001). PEBP4 immunoreactivity in meningioma samples was closely correlated with that for Ki-67 (Spearman r = 0.7922, P < 0.0001). PEBP4 expression was also associated with tumor differentiation grade and clinical recurrence (P < 0.05). Multivariate regression analysis showed with high PEBP4 expression was associated with a longer recurrence-free survival (hazard ratio=0.252, 95% confidence interval: 0.067-0.940, P = 0.040). CONCLUSION: PEBP4 may play an important role in the progression of meningioma, as high PEBP4 expression was associated with a higher pathological grade of meningioma. Moreover, PEBP4 expression may be a meaningful prognostic biomarker in meningioma.

Knockdown of PEBP4 inhibits human glioma cell growth and invasive potential via ERK1/2 signaling pathway.

Phosphatidylethanolamine (PE)-binding protein 4 (PEBP4) is an antiapoptotic protein that is aberrantly expressed in various malignancies. We previously demonstrated that PEBP4 expression is dramatically induced in human gliomas and positively correlated with tumor grade and patient survival. However, the function of PEBP4 in human glioma development and underlying mechanisms remain largely unknown. By stable lentiviral vector-mediated silencing of PEBP4, we examined the effects of PEBP4 knockdown on the growth, apoptosis, and invasion of U251 and U373 human glioma cell lines using MTT, Transwell, colony formation, and flow cytometric assays. We examined the in vivo role of PEBP4 in tumor growth by inoculation of BALB/c nu/nu male mice with PEBP4-deficient U251 and U373 cells. The expression of cell cycle- and apoptosis-related proteins was analyzed by Western blotting and immunostaining. Knockdown of PEBP4 significantly reduced the proliferation and invasion of human glioma cells while inducing cell apoptosis by altering the expression of cell cycle- and apoptosis-related proteins. Mechanistically, PEBP4 knockdown led to activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, an effect that could be reversed by U0126, a selective inhibitor of MEK1/2 (upstream of ERK1/2), suggesting involvement of ERK1/2 signaling in the regulation of glioma development and progression by PEBP4. We identified PEBP4 as a novel regulator mediating human glioma cell proliferation, invasion, and apoptosis as well as tumor formation and growth. Therefore, PEBP4 may be a potential therapeutic target in human glioma treatment.

Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma.

The PTP non-receptor type 4 (PTPN4) is an important regulator protein in learning, spatial memory and cerebellar synaptic plasticity; targeting the PDZ domain of PTPN4 has become as attractive therapeutic strategy for human neuroglioma. Here, we systematically examined the complex crystal structures of PTPN4 PDZ domain with its known peptide ligands; a number of charged amino acid residues were identified in these ligands and in the peptide-binding pocket of PDZ domain, which can constitute a complicated salt-bridge network across the complex interface. Molecular dynamics (MD) simulations, binding free energy calculations and continuum model analysis revealed that the electrostatic effect plays a predominant role in domain-peptide binding, while other noncovalent interactions such as hydrogen bonds and hydrophobic forces are also responsible for the binding. The computational findings were then used to guide structure-based optimization of the interfacial salt-bridge network. Consequently, five peptides were rationally designed using the high-affinity binder Cyto8-RETEV (RETEV-COOH) as template, including four single-point mutants (i.e. Cyto8-mtxe0: RETEE-COOH, Cyto8-mtxd-1: RETDV-COOH, Cyto8-mtxd-3: RDTEV-COOH and Cyto8-mtxk-4: KETEV-COOH) and one double-point mutant (i.e. Cyto8-mtxd-1k-4: KETDV-COOH). Binding assays confirmed that three (Cyto8-mtxd-1, Cyto8-mtxk-4 and Cyto8-mtxd-1k-4) out of the five designed peptides exhibit moderately or considerably increased affinity as compared to the native peptide Cyto8-RETEV.

[Effect of photodynamic therapy combined with interstitial chemotherapy for gliomas].

OBJECTIVE: To investigate the therapeutic effect of photodynamic therapy (PDT) combined with interstitial chemo- therapy on gliomas after microsurgery. METHODS: Twenty-eight patients with glioma received microsurgery for glioma resection as much as possible, during which PDT was carried out and an Ommaya bursa implanted into the cavity left by the resected tumor. PDT was performed again 24 h after the operation and carmustine injected into the Ommaya bursa for interstitial chemotherapy at the different time after the operation. The follow-up study lasted for 2 years. RESULTS: Two of the 28 patients had relapse of glioma within 1 year after the operation, with the 1-year survival rate of 89.3% (25/28) and 2-year survival rate of 65.7% (17/28). CONCLUSIONS: PDT combined with interstitial chemotherapy following microsurgery provides a safe and effective treatment of glioma, which can inhibit glioma growth, decrease the recurrence rate, prolong the patients' survival and improve their quality of live.

[Establishment of canine models of penetrating craniocerebral gunshot wound].

OBJECTIVE: To establish a canine model of penetrating craniocerebral gunshot wound. METHOD: Gunshot wound was induced in 54 cross-bred dogs using 7.62-mm pistol bullets fired using a pistol from a distance of 30 cm in coronal direction with a tilt of 10 degrees toward the orbit, causing penetrating craniocerebral injury 1 cm posterior and 1.5 cm superior to the lateral canthus. The breathing and pathological changes in the brain tissue were observed after the injury. RESULTS: Autonomous breathing was recovered in 9 out of 21 dogs with respiratory arrest after the injury, and the total survival rate was 77.8% in the 54 dogs after the injury. Intracranial hematoma, intracranial pneumatosis, contusion and laceration of brain, and cranial bone fragments were found by cranial CT, with the entrance and exit of the bullet seen on the right and left frontal bone respectively. Pathological examination showed contusion and laceration of the brain tissues. CONCLUSION: The model of craniocerebral perforating wound has been successfully established in dogs.

N-Alkoxyl Templates for Diastereoselective Pyrrolidine Synthesis.

Intramolecular cyclization of N-alkoxyl amines are studied for the stereoselective preparation of 2, 4-disubstituted pyrrolidine derivatives. Reduction of oximes under acidic conditions by NaBH(3)CN afforded the corresponding nucleophilic hydroxylamine derivatives, which subsequently cyclized via S(N)2' mechanism to give the desired N-alkoxyl pyrrolidines.