Mediator Med23 Regulates Adult Hippocampal Neurogenesis.

Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.

Induction chronomodulated chemotherapy plus radiotherapy for nasopharyngeal carcinoma: A Phase II prospective randomized study.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicities of induction chronomodulated chemotherapy in comparison with conventional induction chemotherapy for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between 2003 and 2004, 60 patients with pathologically confirmed NPC were included and randomly assigned to two groups. Patients in the chronomodulated chemotherapy group (n = 30, CC group) received cisplatin at 80 mg/m2 through intravenous infusion from 10:00 to 22:00 and 5-fluorouracil (5-FU) at 1000 mg/m2 plus citrovorum factor at 200 mg/m2 from 22:00 to 10:00 each day for 3 days. Patients in the routine chemotherapy group (n = 30, RC group) received cisplatin infusion within 1 h and 5-FU infusion for about 24 h. The dose in the RC group was the same as that in the CC group. The total irradiation dose in each group was 70 Gy for the whole nasopharynx. RESULTS: One month after induction chemotherapy, the overall response rate was 96.7% in the CC group versus 73.3% in the RC group (P = 0.011). By the end of the 10-year follow-up, 11 patients (36.7%) in the CC group had experienced local recurrence versus 11 patients (36.7%) in the RC group (P > 0.999). The overall survival rates at 1, 5, and 10 years were 96.7%, 53.3%, and 43.3%, respectively, in the CC group, and 96.7%, 43.3%, and 33.3%, respectively, in the RC group (P = 0.346). During induction chemotherapy, the incidence rates of leukocytopenia (43.3% vs. 80%, P = 0.003), thrombocytopenia (26.7% vs. 56.7%, P = 0.018), and nausea/vomiting (40% vs. 66.7%, P = 0.038) were significantly lower in the CC group than in the RC group. The incidence of radiation-induced complications was similar in these two groups. CONCLUSION: Compared with conventional chemotherapy, induction chrono-chemotherapy seemed to reduce chemotherapy-related toxicities and improve average local relapse time in patients treated with combined chemoradiotherapy for NPC.

[Fast Start-up of ANAMMOX and the Spatial Distribution of EPS in ANAMMOX Granules].

An anaerobic sequencing batch reactor(ASBR) inoculated with activated sludge was employed to investigate the start-up of anaerobic ammonium oxidation(ANAMMOX) process and the spatial distribution of extracellular polymeric substances(EPS) in ANAMMOX granules. The results showed that the removal rates of NH4+-N and NO2--N reached more than 99%. The removal rate of total nitrogen(TN) was 89.87%±0.43% and the TN removal load in the ASBR was 1.7 kg·(m3·d)-1. The ratios of nitrite consumption and nitrate production to ammonium consumption were 1.32±0.08 and 0.24±0.03, respectively. Besides, the pH and the effluent nitrate concentration in bulk liquid were considered as two simple indicators for rapid diagnosis of ANAMMOX performance. The proteins(PN) was the main component of EPS in ANAMMOX granular sludge. The PN and polysaccharides(PS) in ANAMMOX granules were (59.61±5.64) mg·g-1 and (12.21±2.04) mg·g-1, respectively, with the ratio of PN/PS reaching approximately 4.88±1.39. ß-D-glucofuranose and dead cells were distributed in the outermost layer of granules, while living cells, PN, lipids, α-glucosamine and α-mannose were distributed throughout the granules and mainly concentrated on the outside of granules. PN and lipids constituted the framework of ANAMMOX granules and ANAMMOX bacteria were embedded among the PN and lipids matrix.

[Comparison of Operating Performance of Partial Nitritation Systems with Two Different Inhibition Strategies].

Two SBRs which were under high ammonia loading[1 kg·(m3·d)-1] and different dual inhibition with feed-batch were employed to study how to control the stability of partial nitritation system. The experimental result showed that the dual inhibition of FNA and DO or FA and DO could implement partial nitrification process at 35℃±1℃ and the ammonia concentration of 1000 mg·L-1. The effluent NO2--N/NH4+-N ratio was about 1, and the effluent NO3--N concentration was close to 0, which was suitable for the appropriate influent for the ANAMMOX. In R1, under the dual inhibition of high FA and low DO concentration, the nitrite oxidizing rate was reduced from 28.16 mg·(g·h)-1 to 0.3 mg·(g·h)-1 (calculated as NO2--N, the same as below). The ammonia oxidizing rate decreased by 43.60%, which was stable at about 20 mg·(g·h)-1 (calculated as NH4+-N, the same as below). In R2,under the dual inhibition of high FNA and low DO concentration, the nitrite oxidizing rate reduced from 12.37 mg·(g·h)-1 to 0.02 mg·(g·h)-1. But the ammonia oxidizing rate remained at a higher level[45 mg·(g·h)-1]. Comparing the nitrification performance of the two SBRs under different control strategies, the dual inhibition of high FNA and low DO concentration had the advantages of short cultivation period, high biological activity and stable operation. It is therefore more suitable for the achievement of the partial nitrification.

Ethanolic Extract of Vitis thunbergii Exhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits.

Vitis thunbergii (VT) is a wild grape that has been shown to provide various cardioprotective effects. The present study was designed to examine whether a VT extract could reduce serum lipid levels and prevent atherogenesis in a hypercholesterolemic rabbit model. At the end of an 8-week study, our results showed that a VT extract supplement markedly suppressed the serum levels of cholesterol and low-density lipoprotein, reduced lipid accumulation in liver tissues, and limited aortic fatty streaks. Our findings suggest that the VT extract activated AMPK (5'-adenosine monophosphate-activated protein kinase) with subsequent inhibition of the activation of ACC (acetyl-CoA carboxylase). Our results suggest that this VT extract could be further developed as a potential lipid-lowering agent and as a natural health food to prevent atherogenesis.