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Aerobic granular sludge (AGS) has been widely applied in pharmaceutical wastewater treatment due to its advantages such as high biomass and excellent settling performance. However, the influence of commonly found antibiotics in pharmaceutical wastewater on the operational efficiency of AGS has been poorly explored. This study investigated the effects of tetracycline (TE) on AGS treating pharmaceutical wastewater at room temperature and analyzed the related mechanisms. The results demonstrate a dose-dependent relationship between TE's effects on AGS. At concentrations below the threshold of 0.1 mg/L, the effects are considered trivial. In contrast, TE with more than 2.0 mg/L reduces the performance of AGS. In the 6.0 mg/L TE group, COD, TN, and TP removal efficiencies decreased to 72.6-75.5, 54.6-58.9, and 71.6-75.8%, respectively. High concentrations of TE reduced sludge concentration and the proportion of organic matter in AGS, leading to a decline in sludge settling performance. Elevated TE concentrations stimulated extracellular polymeric substance secretion, increasing polymeric nitrogen and polymeric phosphorus content. Intracellular polymer analysis revealed that high TE concentrations reduced polyhydroxyalkanoates but enhanced glycogen metabolism. Enzyme activity analysis disclosed that high TE concentrations decreased the activity of key enzymes associated with nutrient removal.

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OBJECTIVE: Perivascular spaces (PVS), components of the glymphatic system in the brain, have been known to be important conduits for clearing metabolic waste, and this process mainly increases during sleep. Sleep disruption might result in PVS dysfunction and cognitive impairment. In this study, we aim to explore whether MRI-visible enlarged perivascular spaces (EPVS) could be imaging markers to predict cognitive impairment in chronic insomnia patients. METHOD: We obtained data from 156 patients with chronic insomnia and 79 age-matched healthy individuals. Using T2-weighted MRI images, visible EPVS in various brain regions were measured and analyzed. The associations between EPVS numbers and cerebrospinal fluid (CSF) ß-amyloid 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) level in chronic insomnia patients were evaluated. RESULT: Our results showed that MRI-visible EPVS in the frontal cortex, centrum semiovale, basal ganglia, and hippocampus of chronic insomnia patients with impaired cognition (ICG) significantly increased than that in normal cognition (NCG) patients. The increased MRI-visible EPVS in the frontal cortex, centrum semiovale, and basal ganglia were also associated with the increased CSF Aß42, t-tau, and p-tau level in ICG patients. MRI-visible EPVS in the basal ganglia and centrum semiovale had high sensitivity and specificity in distinguishing ICG chronic insomnia patients from those with NCG. CONCLUSION: Our study indicated that MRI-visible EPVS in the basal ganglia and centrum semiovale might be valuable imaging markers to predict cognitive impairment in chronic insomnia patients. It will be meaningful to discern those cognitive decline patients in preclinical stage and take some measures to prevent disease progression. KEY POINTS: • Increased MRI-visible EPVS were associated with the increased CSF Aß42, t-tau, and p-tau level in older chronic insomnia patients with impaired cognition.

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To explore the possible mechanism of weight loss in Parkinson's disease (PD). Bilateral injections of 6-hydroxydopamine (6-OHDA) into substantia nigra (SN) were performed to induce the PD model rats. The rotarod test, food intake, body weight, and interscapular brown adipose tissue (IBAT) weight were recorded 6 weeks postoperation. HE staining was performed to observe the morphology of multilocular adipose cells in IBAT. Immunohistochemistry and western blot were used to determine the protein levels of tyrosine hydroxylase (TH) in the SN, and the levels of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), phosphorylated-hormone sensitive lipase (p-HSL), HSL, TH, ß3-adrenergic receptor (ß3-AR), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in IBAT. After treatment with 6-OHDA for 6 weeks, 6-OHDA rats exhibited decreased TH expression in SN accompanied with shortened staying time on the rotating rod. This motor impairment paralleled with no significant alteration in body mass, IBAT weight, and food intake until the end of the experimental protocol. However, the decreasing diameter of the single fat vesicle in IBAT was observed in the 6-OHDA group. Meanwhile, compared with the control group, the protein expression of UCP1, PGC-1α, p-HSL, TH, ß3-AR, cAMP, and PKA in IBAT were increased significantly in the 6-OHDA group, whereas no obvious change in the expression of HSL. The present study suggested an increased energy expenditure and activation of the ß3-AR-cAMP-PKA signaling pathway in the IBAT after the destruction of the dopamine system in the SN of the rat.

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BACKGROUND AND OBJECTIVES: Tracking of the tumor progression by MSCs-based therapy is being increasingly important in evaluating relative therapy effectively. Herein, Bioluminescence imaging (BLI) technology was used to dynamically and quantitatively track the hepatocellular carcinoma suppressive effects by human umbilical cord mesenchymal stem cells (UC-MSCs). METHODS AND RESULTS: The stem cells present typical phenotypic characteristics and differentiation ability by morphology and flow cytometry analysis of marker expression. Then, the growth inhibition effect of conditioned medium and UC-MSC on H7402 cells was studied. It is found both the conditioned medium and UC-MSC can effectively decrease the proliferation of H7402 cells compared with the control group. Meanwhile, the relative migration of UC-MSC to H7402 is also increased through the transwell migration assay. In addition, a mice hepatoma tumor model was built by H7402 cells which can express a pLenti-6.3/DEST-CMV-luciferase 2-mKate2 gene. The effect of stem cells on growth inhibition of tumor in a mice transplantation model was dynamically monitored by bioluminescence imaging within 5 weeks. It has shown the bioluminescence signal intensity of the tumor model was significantly higher than that of the UC-MSC co-acting tumor model, indicating that the inhibition of UC-MSC on liver cancer resulted in low expression of bioluminescent signals. CONCLUSIONS: The microenvironment of UC-MSCs can effectively inhibit the growth of liver cancer cells, and this therapeutic effect can be dynamically and quantitatively monitored in vivo by BLI. This is of great significance for the imaging research and application of stem cells in anticancer therapy.

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Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the associated supratentorial region. The aim of the present study was to analyze the changes in fractional anisotropy (FA) in CCD induced by middle cerebral artery occlusion (MCAO) using magnetic resonance-diffusion tensor imaging (MR-DTI). Furthermore, the role of repulsive guidance molecule a (RGMa) in CCD was assessed by measuring RGMa expression using histochemical analysis. In the present study, the cerebellar hemisphere was serially scanned with T2-weighted, serial diffusion-weighted and diffusion tensor (DT) imaging using a 3.0T GE Signa HDxt Scanner to analyze the changes in FA over 72 h. Subsequently, immunohistochemistry analyses of the corresponding cerebellar hemisphere sections were performed to assess the expression of RGMa. Results indicated that FA of both sides of the cerebellar hemisphere, particularly that of the contralateral cerebellar hemisphere (right side) derived from DTI, was reduced during the 72-h time period following MCAO, and the decrease was maximal and statistically significant at 12 h (P<0.05). Immunohistochemistry analysis revealed a significant increase in the expression of RGMa protein in the affected region of the contralateral cerebellar hemisphere (right side) at 24 h following MCAO injury (P<0.05). Furthermore, the expression of RGMa and FA was negatively correlated in MCAO (P<0.05). The results suggest that MR-DTI is an important assessment to evaluate changes of FA in CCD induced by MCAO. Furthermore, the present results suggest that RGMa, which was negatively correlated with FA in MCAO rats, may serve an important role in CCD.

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MicroRNA­375 (miR­375) serves an important role in cancer development and growth. However, little is known about the role of miR­375 in the regulation of oral squamous cell carcinoma (OSCC) metastasis and invasion. The present study measured the expression levels of miR­375 in Tca8113, UM2, UM1 and CAL­27 cell lines, using reverse transcription­quantitative polymerase chain reaction. The results demonstrated that miR­375 expression levels were significantly reduced in UM1 and CAL­27 (highly metastatic) compared with Tca8113 and UM2 (less aggressive) OSCC cell lines. Furthermore, it was revealed that overexpression of miR­375 suppressed the migration and invasion of UM1 cells. Based on a luciferase reporter assay, platelet­derived growth factor­A (PDGF­A) was identified as a direct target gene of miR­375. Additionally, overexpression of PDGF­A significantly reversed the effect of miR­375 on cell migration and invasion in UM1 cells. These data demonstrated that miR­375 suppressed OSCC cell migration and invasion by targeting PDGF­A, which may be a potential therapeutic target for the treatment of OSCC.

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