Expression Profiles of Matrix Metalloproteinases and Their Inhibitors in Nasal Polyps.

Purpose: Nasal polyp (NP) is characterized by inflammation of the sinonasal mucosa with predominant inflammatory cell infiltration. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are recognized to play an important role in leukocyte migration in airway inflammation. Herein, efforts were made to confirm the expression levels of MMPs/TIMPs and study the relationship between the infiltration of inflammatory cells and local expression levels of MMPs/TIMPs in NPs. Patients and Methods: NP tissues were obtained from 42 Chinese patients with bilateral nasal polyps during the endoscopic sinus surgery. Inferior turbinate (IT) tissues from 19 patients with septal deviation were taken during the rhinoplasty surgery as controls. mRNA and protein levels of MMP1, MMP9, MMP10, MMP12, TIMP1 and TIMP3 were assessed by quantitative PCR and immunohistochemistry. Results: Eosinophilia (72%, 23/32 samples), neutrophilia (41%, 13/32 samples), and increase in macrophages (38%, 12/32 samples) were found in NP tissues. mRNA expression of MMP1 (10.9-fold), MMP9 (4.1-fold), MMP10 (6.7-fold) and MMP12 (3.5-fold) were significantly up-regulated, while TIMP1 (1.5-fold) and TIMP3 (6.0-fold) were significantly down-regulated in NPs (n=42) as compared to the controls (n=19). The immunostaining levels of all 4 MMPs and two TIMPs were higher in NPs than those in controls. The co-localization of MMP1/MMP10/MMP12 and macrophages were identified in NPs. MMP9 was mainly expressed in neutrophils, while TIMP1 or TIMP3 were mostly found in eosinophils in NPs. Conclusion: The results of our study indicate that tissue remodeling is significant in NPs, where MMPs/TIMPs play important roles in both tissue remodeling and inflammatory cells infiltration.

Associations Between Mild Cognitive Impairment and Whole Blood Zinc and Selenium in the Elderly Cohort.

Some studies have shown that an imbalance in trace element homeostasis can lead to cognitive dysfunction, but data are lacking. The purpose of this study was to investigate the association between whole blood zinc (Zn), selenium (Se), copper-zinc ratio (Cu/Zn), copper-selenium ratio (Cu/Se), and zinc-selenium ratio (Zn/Se) and mild cognitive impairment (MCI) in elderly Chinese individuals. The study was based on the Elderly Health and Controlled Environmental Factors Cohort in Lu'an, Anhui Province, China, from June to September 2016. The cognitive function of the elderly was determined by the Mini-Mental State Examination (MMSE) and activities of daily living (ADL) scales. The concentrations of Zn, Cu, and Se in the whole blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Binary logistic regression was used to analyze the associations between trace elements and MCI. A total of 1006 participants with an average age of 71.70 years old were included in this study. Compared with healthy people, MCI patients had higher whole blood Zn levels and lower Se levels, and Cu/Zn, Cu/Se, and Zn/Se were also significantly different. Binary logistic regression analysis showed that Zn, Cu/Se, and Zn/Se exposure in the third tertile was associated with an increased risk of MCI, while Se exposure in the third tertile was associated with a reduced risk of MCI. After adjustment for sex, age, marital status, BMI, and living status, whole blood Zn, Se, Cu/Zn, Cu/Se, and Zn/Se were significantly associated with MCI risk, especially in elderly women.

Increased hypertension risk for the elderly with high blood levels of strontium and lead.

Hypertension has long been recognized as the global health burden. Heavy metal pollution may be one of the environmental risk factors of hypertension. However, the association remains unclear. We studied the levels of aluminum (Al), vanadium (V), manganese (Mn), arsenic (As), selenium (Se), strontium (Sr), barium (Ba), titanium (Ti), lead (Pb) and cobalt (Co) in whole blood, and the relationship between trace element exposure and hypertension in the elderly community-based Chinese population. A total of 1013 participants from the west of Anhui Province in China were consecutively enrolled in this study in 2016. The general sociodemographic characteristics, lifestyles, disease history and physical examination information were collected by face-to-face survey and physical examination. The levels of ten trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regression model was used to assess the association of trace element exposure with the risk of hypertension. Results showed that the odds ratio of hypertension in the highest quartile was 1.811 (95% CI 1.175-2.790, P trend = 0.005) and 1.772 (95% CI 1.121-2.800, P trend = 0.022), respectively, after adjusting for potential confounders, as compared with the lowest quartile of blood Pb and Sr levels.

Usefulness of four surrogate indexes of insulin resistance in middle-aged population in Hefei, China.

OBJECTIVE: Previous study have shown that lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) and triglycerides/glucose index (TyG index) could be simple clinical indicators of insulin resistance (IR) based on anthropometric and/or biochemical parameters. However, the rational and preferred surrogate marker of IR in different population has yet to be validated. The aim of this study was evaluating the practicability of the LAP, VAI, TG/HDL-C, and TyG in predicting IR in middle-aged Chinese population. METHODS: A cross-sectional study was conducted in 569 Chinese participants (mean age was 48.5; man 67.7%), and each participant completed a questionnaire survey, anthropometric measurement, and biochemical testing. One-way ANOVAs, Chi-squared test, Pearson's correlation, and multiple logistic regression were used to evaluate the association between VAI, LAP, TG/HDL-C, and TyG with IR. To correctly discriminate individuals with insulin resistance, a receiver operating characteristic (ROC) analysis was conducted for each evaluated variable and the overall diagnostic accuracy was quantified using the area under the ROC curve (AUC). The AUC of evaluated variables were compared using a nonparametric approach. The optimal cut-off points were determined by the Youden's index, and the corresponding sensitivity and specificity were provided. RESULTS: Significant positive correlation was identified between HOMA-IR with TG/HDL-C (r = 0.306), VAI (r = 0.217), LAP (r = 0.381), and TyG (r = 0.371), respectively (all p < .001). After adjustment for potential confounders of IR, compared with the lowest tertiles, odds ratio (95% CI) having IR in the highest tertiles of TG/HDL-C, VAI, LAP and TyG were 6.07 (2.89-12.71), 10.89 (4.37-27.13), 4.68 (2.00-10.92), and 12.20 (5.04-29.56). The area under ROC curves to predict HOMA-diagnosed IR was 0.773 for TG/HDL-C, 0.767 for VAI, 0.806 for LAP, and 0.800 for TyG, respectively. Among those, LAP showed the greatest value of AUC [0.806 (0.763-0.850)] and highest specificity (0.804). CONCLUSION: Compared with other indicators, the LAP and TyG are simple, relatively accurate, clinically available surrogate markers of insulin resistance in middle-aged population in Hefei, China. Among 4 evaluated parameters, the LAP have the highest specificity and the TyG have the highest sensitivity.Key MessagesLAP and TyG could be used as simple and alternative methods to identify the individuals at risk for insulin resistance.LAP and TyG have relatively high predictive ability in diagnosis of IR compared with VAI and TG/HDL-C.No significant difference is observed between LAP and TyG in the ability of predicting insulin resistance.

Continuous supplementation of folic acid in pregnancy and the risk of perinatal depression-A meta-analysis.

BACKGROUND: The blood folic acid1(FA) level of depressed patients seems to be lower than that of normal, and pregnant women are at greater risk of FA deficiency. The relationship between FA and perinatal depression has not been well described. METHODS: We conducted a meta-analysis of the evidence for the association between the two, using current FA supplementation behavior during pregnancy and blood FA levels as exposures, and the incidence of perinatal depressive symptoms and mean Edinburgh Postnatal Depression Scale2 (EPDS) scores as outcomes. The present study was recorded in PROSPERO (2019 CRD: 42,020,211,509). RESULTS: Fifteen studies were identified, covering a total of 26,275 women from eleven observational studies and four randomized controlled trials. For the primary outcome of folic acid supplementation behavior and risk of perinatal depression, the overall odds ratio was 0.742 (95% CI: (0.647-0.852)), with a combined effect value of 0.84 (95% CI: (0.76, 0.93)) for studies in which an OR could be extracted. A negative association was observed between blood folate levels and depressive symptoms (Standardized mean difference (SMD) =-0.127, 95% CI:(-0.183,-0.071)). No association was observed between folic acid intervention and EPDS score. Continuous supplementation of folic acid during pregnancy may reduce the incidence of perinatal depressive symptoms (R = 0.017, (95 CI%:(0.014, 0.021)). LIMITATIONS: Lack of rigorous randomized controlled trials due to ethical issues, and the research is heterogeneous and does not consider the influence of genetic factors. CONCLUSIONS: Continuous use of FA during pregnancy may reduce the incidence of perinatal depressive symptoms.

[Analysis of clinical characteristics of fungal ball in unilateral maxillary sinus].

Objective:The aim of this study is to investigate the pathological characteristics of unilateralmaxillary sinus fungus ball（UMFB） in order to improve the accuracy of clinical diagnosis. Methods:A total of 86 patients with unilateral maxillary sinus lesions who underwent nasal endoscopic surgery in Qilu Hospital of Shandong University（Qingdao） from January 2017 to June 2019 were included. Those patients were confirmed UMFB or unilateral chronic maxillary sinusitis（UCMS） by pathology. The characteristics including age, sex, diabetes mellitus or no, CT features of the diseased maxillary sinus and GOSS osteitis score of the posterolateral wall of the maxillary sinus were analyzed, and the differences between the two groups were compared. CT features include: ①intralesional hyperdensity（calcification）; ②maxillary sinus full haziness with or without mass effect; ③the irregular lobulated protruding lesion（fuzzy appearance） or smooth. Chi-square, independent sample t test and Mann-Whitney U test were performed. Logistic regression analysis and receiver operating Characteristic（ROC） curve analysis were used to find the best cutoff value for UMFB diagnosis. Results:Among the 86 cases of unilateral maxillary sinus lesions, 62 cases were UMFB, which accounted for 72.1%, and 24 cases were UCMS, which accounted for 27.9%. UMFB usually occurs in middle-aged and elderly patients, and there are more females than males. There was no statistical difference between the two groups with or without diabetes. In terms of CT characteristics of paranasal sinuses, intergroup comparison and binary Logistic regression analysis, intralesional hyperdensity, maxillary sinus full haziness with mass effect, the irregular lobulated protruding lesion（fuzzy appearance） were significant predictors of MFB（all P<0.05）. The score of osteitis in UMFB was significantly higher than that in UCMS（P<0.001）. ROC curve analysis showed that when the cutoff value was more than 3.5（the area under the curve was 0.824）, the corresponding sensitivity and specificity were 0.516 and 0.958, respectively. Conclusion:The age, gender, CT characteristics and maxillary sinus osteitis score can distinguish UMFB from unilateral maxillary sinus chronic inflammation, and improve the accuracy of clinical diagnosis.

Combined coagulation/decantation-ozone/hydrogen peroxide-biological aerated filter process for advanced treatment of bio-treated leachate from Chinese herbal medicine residue.

To reach discharge limit, further treatment of bio-treated leachate from Chinese herbal medicine residue (BLCHMR) was very imperative. In this study, performance of combined coagulation/decantation-ozone/hydrogen peroxide (O3/H2O2)-biological aerated filter (BAF) technology used to further treat BLCHMR was investigated with pilot-scale experiment. Under optimal conditions, the COD (40-44 mg/L) and color (13-17 time) in treated BLCHMR indicated that combined process can efficiently treat BLCHMR. O3/H2O2 had good performance not only in mineralization and decomposing of organic matter but also in decolorization of BLCHMR. For dissolved organic matter (DOM), O3/H2O2 reacted with non-biodegradable fraction preferentially and oxidized different molecular weight (MW) fractions equally. O3/H2O2-BAF generated more higher MW DOM (namely F2 fraction) than BAF alone. Meanwhile, O3/H2O2 mainly influenced the amount and biodegradability on DOM but not the removal rate on DOM. Accordingly, the helpful influence on O3/H2O2 perhaps can be owed to the generalized influence on DOM but not the specific influence on improved biodegradability. Finally, inspiring (namely very low) cost (respectively, 0.3419 $/per ton bio-treated leachate and 0.5766 $/Kg COD removed) was achieved in the combined process.

Novel Poly(ADP-ribose) Polymerase-1 Inhibitor DDHCB Inhibits Proliferation of BRCA Mutant Breast Cancer Cell In Vitro and In Vivo through a Synthetic Lethal Mechanism.

Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are drugs that are effectively used to treat breast cancer. We synthesized a novel bromophenol derivative ethyl (E)-4-(2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamido)benzoate (DDHCB) as a novel PARP-1 inhibitor. Our study found that DDHCB could inhibit PARP-1 activity with an IC50 value of 58.3 nM. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide (MTT) assay indicated that DDHCB could selectively inhibit proliferation of BRCA mutant cells and demonstrate the ability of synthetic lethality. DDHCB could also induce DNA double-strand breaks with the ability to increase the foci quantitation of γ-H2AX. Moreover, DDHCB could increase PARP-1-DNA trapping and inhibit PAR formation in HCC-1937 cells. Further investigation showed that DDHCB induced apoptosis and G2/M cycle arrest. Finally, we found that DDHCB inhibited the growth of HCC-1937 xenografts with low toxicity. In vivo mechanisms showed that the level of γ-H2AX was increased in the DDHCB-treated tumors, indicating the PARP-1 inhibition ability of DDHCB in vivo. Our study results indicated that the future development of DDHCB for the treatment of breast cancer is promising.

BTH-8, a novel poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, causes DNA double-strand breaks and exhibits anticancer activities in vitro and in vivo.

Poly (ADP-ribose) polymerase (PARP) is a family of enzymes that play an important role in DNA repair. We designed 2-(2,3,6-tribromo-4,5-dimethoxybenzylidene) hydrazinecarbothioamide (BTH-8) as a novel human PARP (PARP-1) inhibitor with anticancer activities in vitro and in vivo. With an IC50 value of 79.79 ± 2.16 nM, BTH-8 caused DNA double-strand breaks, increased the foci quantitation of γ-H2AX and inhibited poly(ADP-ribose) (PAR) formation. BTH-8 could bind to PARP-1 with the target affinity [KD (equilibrium dissociation constant) value] of 1.372 µM. BTH-8 can inhibit the proliferation of a variety of tumor cells, especially BRCA-deficient cells (HCC-1937 and Capan-1). Further investigation showed that BTH-8 effectively induced a significant amount of G2/M cell cycle arrest and cell apoptosis in HCC-1937 cells. BTH-8 also exhibited antitumor activity in vivo, which was achieved by the inhibition of PARP-1. In sum, our study indicates that BTH-8 might be a novel suitable PARP-1 inhibitor to treat human breast cancer.

The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo.

The eIF4E/eIF4G complex plays a central role in gene expression regulation during the initial stage of translation. This study aimed to determine if the novel small molecule compound, TPDHT, could disrupt the interaction of eIF4E/eIF4G, and if it could exhibit excellent antitumor activity in vivo without causing apparent toxicity effect. This study investigated the antitumor mechanism of TPDHT in vitro and in vivo. TPDHT showed significant anti-proliferative activity on human lung cancer A549 cells, and it induced G0/G1 cycle arrest. Moreover, TPDHT also induced A549 cell apoptosis through the mitochondria-mediated apoptotic pathway. Our results indicate that TPDHT could disrupt the interaction of eIF4E/eIF4G, and the activity of eIF4F plays an important role in TPDHT-induced cell proliferation inhibition and apoptosis. Further research showed that TPDHT could inhibit the Ras/ERK/MNK pathway, and activation of the ERK pathway reversed TPDHT-induced cell proliferation inhibition and apoptosis. Taken together, our study findings indicated that TPDHT exerts an antitumor effect through an intrinsic apoptotic pathway controlled by the ERK/MNK/eIF4F pathway.

Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E/eIF4G as multifunctional agents for cancer treatment.

The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazolylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of eIF4E by inhibiting the phosphorylation of eIF4E and 4EBP1, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases.

Discovery of Novel Bromophenol-Thiosemicarbazone Hybrids as Potent Selective Inhibitors of Poly(ADP-ribose) Polymerase-1 (PARP-1) for Use in Cancer.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a new potential target for anticancer drug discovery. A series of bromophenol-thiosemicarbazone hybrids as PARP-1 inhibitors were designed, synthesized, and evaluated for their antitumor activities. Among them, the most promising compound, 11, showed excellent selective PARP-1 inhibitory activity (IC50 = 29.5 nM) over PARP-2 (IC50 > 1000 nM) and potent anticancer activities toward the SK-OV-3, Bel-7402 and HepG2 cancer cell lines (IC50 = 2.39, 5.45, and 4.60 µM), along with inhibition of tumor growth in an in vivo SK-OV-3 cell xenograft model. Further study demonstrated that compound 11 played an antitumor role through multiple anticancer mechanisms, including the induction of apoptosis and cell cycle arrest, cellular accumulation of DNA double-strand breaks, DNA repair alterations, inhibition of H2O2-triggered PARylation, antiproliferative effects via the production of cytotoxic reactive oxygen species, and autophagy. In addition, compound 11 displayed good pharmacokinetic characteristics and favorable safety. These observations demonstrate that compound 11 may serve as a lead compound for the discovery of new anticancer drugs.

Correction: APTES assisted surface heparinization of polylactide porous membranes for improved hemocompatibility.

[This corrects the article DOI: 10.1039/C6RA04525A.].

Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma.

Aim of the investigation was to develop folate-functionalized lipid nanoemulsion (LNE) comprising chemo-radiotherapeutics for targeted delivery to nasopharyngeal carcinoma (NPC). Soy lecithin nanoemulsion of doxorubicin (Dox) and yittrium-90 (90Y) was prepared by nanoprecipitation using ultrasonic homogenization technique followed by folic acid conjugation. Nanoemulsion (Dox-LNE) was characterized as positively charged (zeta potential), spherical shape (transmission electron microscopy) nano-droplets of uniform size distribution (polydispersity index). No significant variation in parameters such as particle size, zeta potential, and polydispersity index was observed when the stability of Dox-LNE was assessed during long-term storage at room temperature and at 8000 rpm, 121°C temperature, and 5000 time dilution in water. In vitro release of Dox from Dox-LNE was observed to be controlled for at least 48 h. Folate decoration over Dox-LNE surface (FD-Dox-LNE) and incorporation of 90Y in FD-Dox-LNE (FD-Dox + 90Y-LNE) changed droplet size up to 50 nm; however, surface charge of Dox-LNE did not change significantly. FD-Dox + 90Y-LNE inhibited growth of cancerous cell line like CNE1 (folate receptor rich) in vitro and alleviated tumor volume in NPC-induced nude mice significantly as compared to Dox + 90Y-LNE. Massive necrosis and hemorrhage of CNE1 cells were observed by FD-Dox + 90Y-LNE (89.9%); however, inhibition of growth of nasal epithelial cells (RPMI 2650; folate deficient) by FD-Dox + 90Y-LNE and Dox + 90Y-LNE was observed to be 21.5 and 43.65%, respectively. The investigation highlights the vast utility of folate-decorated lipid emulsion in delivering chemo-radiotherapeutics to the specific NPC site. FD-Dox + 90Y-LNE might offer a cost-effective, safe, efficacious, and clinically pertinent option to the available therapeutics.

Caveolin-1 is overexpressed in hypopharyngeal squamous cell carcinoma and correlates with clinical parameters.

The present study aimed to identify the role of caveolin-1 (CAV1) in hypopharyngeal squamous cell carcinoma (HSCC) and identify its possible correlation with tumor clinical parameters. Expression of CAV1 was measured using immunohistochemical staining of 66 HSCC samples and 44 samples from morphologically normal tissues adjacent to the carcinomas. Expression of CAV1 in HSCC and paracancerous tissues were 71.2 and 9.5% respectively. Levels of CAV1 expression were significantly associated with tumor differentiation, tumor-node-metastasis stage and lymph nodes metastasis (P<0.05). The present study identified that expression of CAV1 in HSCC is significantly higher than in paracancerous tissues, suggesting that this high expression of CAV1 is associated with tumor invasion and metastasis.

Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2-Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization, and Performance.

Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling capability and hemocompatibility were developed using poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate) (PLA-PHEMA) copolymers as the blending additive. PLA-PHEMA block copolymers were synthesized via reversible addition-fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H NMR) were applied to characterize the synthesized products. By blending PLA with the amphiphilic block copolymer, PLA/PLA-PHEMA membranes were prepared by nonsolvent induced phase separation (NIPS) method. Their chemistry and structure were characterized with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results revealed that PLA/PLA-PHEMA membranes with high PLA-PHEMA contents exhibited enhanced hydrophilicity, water permeability, antifouling and hemocompatibility. Especially, when the PLA-PHEMA concentration was 15 wt %, the water flux of the modified membrane was about 236 L m(-2) h(-1). Its urea and creatinine clearance was more than 0.70 mL/min, lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31 mL/min. All the results suggest that PLA-PHEMA copolymers had served as effective agents for optimizing the property of PLA-based membrane for hemodialysis applications.

Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma.

The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes.

Performance and microbial diversity of an expanded granular sludge bed reactor for high sulfate and nitrate waste brine treatment.

The disposal of waste brines has become a major challenge that hinders the wide application of ion-exchange resins in the water industry in recent decades. In this study, high sulfate removal efficiency (80%-90%) was achieved at the influent sulfate concentration of 3600 mg/L and 3% NaCl after 145 days in an expanded granular sludge bed (EGSB) reactor. Furthermore, the feasibility of treating synthetic waste brine containing high levels of sulfate and nitrate was investigated in a single EGSB reactor during an operation period of 261 days. The highest nitrate and sulfate loading rate reached 6.38 and 5.78 kg/(m(3)·day) at SO(2-)4-S/NO(-)3-N mass ratio of 4/3, and the corresponding removal efficiency was 99.97% and 82.26% at 3% NaCl, respectively. Meanwhile, 454-pyrosequencing technology was used to analyze the bacterial diversity of the sludge on the 240th day for stable operation of phase X. Results showed that a total of 9194 sequences were obtained, which could be affiliated to 14 phyla, including Proteobacteria, Firmicutes, Chlorobi, Bacteroidetes, Synergistetes and so on. Proteobacteria (77.66%) was the dominant microbial population, followed by Firmicutes (12.23%) and Chlorobi (2.71%).

The Expression of SIRT1 and DBC1 in Laryngeal and Hypopharyngeal Carcinomas.

RATIONALE AND OBJECTIVE: Sirtuin 1 (SIRT1) plays an important role in tumorigenesis and is increased in many human tumors. DBC1 is a negative regulator of SIRT1 via promotion of p53-mediated apoptosis. It is necessary to investigate the expression of SIRT1 and DBC1 in laryngeal and hypopharyngeal squamous cell carcinomas (LSCC and HSCC) and its correlation with available clinical parameters. METHODS: The mRNA levels of SIRT1 and DBC1 were measured in 54 paired LSCC or HSCC tumors and corresponding adjacent noncancerous mucosae using quantitative RT-PCR (qRT-PCR). The protein levels of SIRT1 and DBC1 were also evaluated in 120 cases of patients with LSCC or HSCC using immunohistochemical staining. The correlation between SIRT1 and DBC1 expression and clinical parameters was analyzed with Pearson chi-square test. RESULTS: qRT-PCR assay showed that, compared with the paired adjacent noncancerous mucosae, SIRT1 mRNA was significantly decreased in tumors. The immunohistochemical results indicated that the SIRT1 protein was also downregulated in tumors compared with noncancerous mucosae. Moreover, decreased SIRT1 was significantly correlated with the tumor clinical stage and lymph node metastasis. Additionally, DBC1 mRNA was significantly increased in tumors compared with noncancerous mucosae. The immunohistochemical results indicated that the DBC1 protein was downregulated in tumors, which is inconsistent with the results obtained by qRT-PCR. Finally, decreased DBC1 protein was significantly correlated with tumor differentiation, lymph node metastasis, and p53 expression. CONCLUSIONS: SIRT1 and DBC1 might be involved in the pathophysiology of laryngeal and hypopharyngeal squamous cell carcinomas and are associated with lymph node metastasis and p53 positive staining in LSCCs and HSCCs.