The Burden of Occupational Noise-Induced Hearing Loss From 1990 to 2019: An Analysis of Global Burden of Disease Data.

OBJECTIVES: The relationship between long-term exposure to occupational noise and hearing loss has been extensively documented. We aimed to assess spatial and temporal changes in the burden of occupational noise-induced hearing loss (ONIHL) in 204 countries and territories with varying socio-demographic indexes (SDI) from 1990 to 2019. DESIGN: Temporal and spatial trends in age-standardized disability-adjusted life year rates (ASDR) for ONIHL were estimated by sex, age, SDI level, country, and geographic region from 1990 to 2019. We used the Joinpoint model to calculate annual average percentage changes to assess such trends and projected trends in ASDR for ONIHL globally and across different income regions from 2020 to 2044 using an age-period-cohort model. We fitted the relationship between ASDR and SDI, ASDR and healthcare access and quality index, respectively. RESULTS: Overall, the global burden of ONIHL has decreased since 1990, especially in middle and lower SDI regions. In 2019, the global ASDR for ONIHL was 84.23 (95% confidence interval: 57.46 to 120.52) per 100,000 population. From 1990 to 2019, the global ASDR for ONIHL decreased by 1.72% (annual average percentage change = -0.05, 95% confidence interval: -0.07 to -0.03). Our projections showed a decreasing trend in the global ONIHL burden until 2044. ASDR and SDI (R = -0.8, p < 0.05), ASDR and healthcare access and quality index (R = -0.75, p < 0.05) showed significant negative correlations. CONCLUSIONS: The global ONIHL burden has decreased over the past three decades, especially in regions with middle and lower SDI levels. However, the global ONIHL burden still remained severe in 2019, notably among males, the middle-aged and elderly, and regions with lower SDI levels.

Sulforaphane-Enriched Extracts from Broccoli Exhibit Antimicrobial Activity against Plant Pathogens, Promising a Natural Antimicrobial Agent for Crop Protection.

Sulforaphane (SFN) is one of the hydrolysates of glucosinolates (GSLs), primarily derived from Brassica vegetables like broccoli. In clinical therapy, SFN has been proven to display antimicrobial, anticancer, antioxidant, and anti-inflammatory properties. However, the antimicrobial effects and mechanism of SFN against plant pathogens need to be further elucidated, which limits its application in agriculture. In this study, the genetic factors involved in SFN biosynthesis in 33 B. oleracea varieties were explored. The finding showed that besides the genetic background of different B. oleracea varieties, myrosinase and ESP genes play important roles in affecting SFN content. Subsequently, the molecular identification cards of these 33 B. oleracea varieties were constructed to rapidly assess their SFN biosynthetic ability. Furthermore, an optimized protocol for SFN extraction using low-cost broccoli curds was established, yielding SFN-enriched extracts (SFN-ee) containing up to 628.44 µg/g DW of SFN. The antimicrobial activity assay confirmed that SFN-ee obtained here remarkably inhibit the proliferation of nine tested microorganisms including four plant pathogens by destroying their membrane integrity. Additionally, the data demonstrated that exogenous application of SFN-ee could also induce ROS accumulation in broccoli leaves. These results indicated that SFN-ee should play a dual role in defense against plant pathogens by directly killing pathogenic cells and activating the ROS signaling pathway. These findings provide new evidence for the antimicrobial effect and mechanism of SFN against plant pathogens, and suggest that SFN-ee can be used as a natural plant antimicrobial agent for crop protection and food preservation.

Effects and mechanism of metal ions on the stability of glucosinolates in aqueous solution.

Glucosinolates (GLs) are important precursors of anticancer isothiocyanates in cruciferous plants. However, GLs in aqueous solution have been found to decompose under certain conditions, and the effect of metal ions remains unclear. In this study, high-purity glucoraphanin and glucoraphenin were used to explore the effects of metal ions with thermal treatment. The degree of GLs decomposition was affected by the type and concentration of metal ions, temperature, and duration of heating. Fe3+ (1 mM) was found to cause the decomposition of 78.1 % of glucoraphanin and 94.7 % of glucoraphenin in 12 h at 100 °C, while Cu2+ completely decomposed both GLs. The decomposition products were all the corresponding nitriles, and decomposition dynamic curves were first-order. In addition to accelerating hydrolysis, metal ions may promote the generation of nitriles as catalysts. The exploration of GLs decomposition could help to adopt more effective methods to avoid the formation of toxic compounds.

Diabetes risk among US adults with different socioeconomic status and behavioral lifestyles: evidence from the National Health and Nutrition Examination Survey.

Background: Diabetes disproportionately affects minorities and those with low socioeconomic status (SES) in the United States, and differences in behavioral lifestyles are largely responsible for the unequal distribution of diabetes among different groups. Methods: With data of 9,969 participants collected in the 2007-2008 and 2009-2010 cycles of the US National Health and Nutrition Examination Survey (NHANES), this study examined several mediators and their mediating effects in the connection between SES and the risk of diabetes. The SES is assessed by the income-to-poverty ratio (IPR), education level, and employment status. For the mediation analysis, we used health-related behaviors as mediators (smoking, alcohol use, consumption of green vegetables and fruits, physical activity and sedentary time, health insurance, and healthcare). In this study, the structural equation model was utilized to evaluate the mediating effects of behavioral lifestyle as a mediator in the relationship between SES and diabetes. Results: A total of 9,969 participants were included in this study. We found a negative nonlinear association between IPR and diabetes risk (Poverall < 0.001; Pnon-linear = 0.46), which was independent of the majority of known or suspected risk factors and confounding variables (gender, age, race). Participants with lower SES had higher risk of diabetes compared with those with higher SES. In mediating analysis, we found alcohol intake (OR = 0.996), physical activity (OR = 0.993), health insurance (OR = 0.998), and healthcare (OR = 1.002) mediated the IPR-diabetes association. But in the relationship between education status and diabetes, the mediation effect of alcohol intake (OR = 0.995), physical activity (OR = 0.991), and health care (OR = 1.008) were obvious. Likewise, alcohol intake (OR = 0.996), fruit intake (OR = 0.998), and health care (OR = 0.975) were important mediators in the association between employment status and diabetes. Conclusion: This study provides critical insights on the link between SES and diabetes. Our results highlight that poor health-related behaviors and limited access to healthcare are important pathways for increased diabetes risk related to those with low SES, particularly among Mexican Americans and males. They should be top priorities for agencies and healthcare providers to develop behavior-related interventions to reduce inequalities in diabetes risk.

Chemically stable fluorescent proteins for advanced microscopy.

We report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), 'hyperfolder YFP' (hfYFP), that withstands chaotropic conditions that denature most biological structures within seconds, including superfolder green fluorescent protein (GFP). hfYFP contains no cysteines, is chloride insensitive and tolerates aldehyde and osmium tetroxide fixation better than common fluorescent proteins, enabling its use in expansion and electron microscopies. We solved crystal structures of hfYFP (to 1.7-Å resolution), a monomeric variant, monomeric hyperfolder YFP (1.6 Å) and an mGreenLantern mutant (1.2 Å), and then rationally engineered highly stable 405-nm-excitable GFPs, large Stokes shift (LSS) monomeric GFP (LSSmGFP) and LSSA12 from these structures. Lastly, we directly exploited the chemical stability of hfYFP and LSSmGFP by devising a fluorescence-assisted protein purification strategy enabling all steps of denaturing affinity chromatography to be visualized using ultraviolet or blue light. hfYFP and LSSmGFP represent a new generation of robustly stable fluorescent proteins developed for advanced biotechnological applications.

A global burden assessment of lung cancer attributed to residential radon exposure during 1990-2019.

This study aimed to explore the spatial and temporal trends of lung cancer burden attributable to residential radon exposure at the global, regional, and national levels. Based on the Global Burden of Disease Study (GBD) 2019, we collected the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life rate (ASDR) of lung cancer attributable to residential radon exposure from 1990 to 2019. The Joinpoint model was used to calculate the annual average percentage change (AAPC) to evaluate the trend of ASMR and ASDR from 1990 to 2019. The locally weighted regression (LOESS) was used to estimate the relationship of the socio-demographic index (SDI) with ASMR and ASDR. In 2019, the global ASMR and ASDR for lung cancer attributable to residential radon exposure were 1.03 (95% CI: 0.20, 2.00) and 22.66 (95% CI: 4.49, 43.94) per 100 000 population, which were 15.6% and 23.0% lower than in 1990, respectively. According to the estimation, we found the lung cancer burden attributable to residential radon exposure declined significantly in high and high-middle SDI regions, but substantially increased in middle and low-middle SDI regions from 1990 to 2019. Across age and sex, the highest burden of lung cancer attributable to residential radon exposure was found in males and elderly groups. In conclusion, the global burden of lung cancer attributable to residential radon exposure showed a declining trend from 1990 to 2019, but a relatively large increase was found in the middle SDI regions. In 2019, the burden of lung cancer attributable to residential radon exposure remained high, particularly in males, the elderly, and high-middle SDI regions compared with other groups.

Dissection-related carotid-cavernous fistula (CCF) following surgical revascularization of chronic internal carotid artery occlusion: a new subtype of CCF and proposed management.

BACKGROUND: The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting. METHODS: Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography. RESULTS: All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete (n = 4) or partial CCF (n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients. CONCLUSIONS: Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery.

Secondary Metabolites from Solanum rostratum and Their Antifeedant Defense Mechanisms against Helicoverpa armigera.

Solanum rostratum is a worldwide malignant invasive weed, causing serious harm to the ecological environment and biodiversity. Strong chemical defense against herbivorous insects is supposed to be one of the successful invasive mechanisms of this exotic plant. However, the real defense components and their action mechanisms and distributions are still unknown. To address these problems, we bioassay-guided isolated compounds from the aerial part of S. rostratum and determined their structures using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance, and electronic circular dichroism calculation. One new and seven known compounds were identified, and all of the isolates exhibited different levels of antifeedant activities, especially compounds 1 and 4. Consistently, compounds 1 and 4 displayed potent inhibitory effects on antifeedant-related enzymes (AchE and CarE). The action mechanisms of active compounds 1 and 4 were revealed by molecular docking and molecular dynamic simulation studies. Furthermore, the distributions of the active compounds in leaves, stems, and flowers were also analyzed by liquid chromatography-mass spectrometry.

[Lung nodule segmentation based on fuzzy c-means clustering and improved random walk algorithm].

Accurate segmentation of pulmonary nodules is an important basis for doctors to determine lung cancer. Aiming at the problem of incorrect segmentation of pulmonary nodules, especially the problem that it is difficult to separate adhesive pulmonary nodules connected with chest wall or blood vessels, an improved random walk method is proposed to segment difficult pulmonary nodules accurately in this paper. The innovation of this paper is to introduce geodesic distance to redefine the weights in random walk combining the coordinates of the nodes and seed points in the image with the space distance. The improved algorithm is used to achieve the accurate segmentation of pulmonary nodules. The computed tomography (CT) images of 17 patients with different types of pulmonary nodules were selected for segmentation experiments. The experimental results are compared with the traditional random walk method and those of several literatures. Experiments show that the proposed method has good accuracy in the segmentation of pulmonary nodule, and the accuracy can reach more than 88% with segmentation time is less than 4 seconds. The results could be used to assist doctors in the diagnosis of benign and malignant pulmonary nodules and improve clinical efficiency.

Discs large homolog 1 regulates B-cell proliferation and antibody production.

Antibody production results from B-cell activation and proliferation upon antigen binding. Discs large homolog 1 (Dlg1), a scaffold protein from the membrane-associated guanylate kinase family, has been shown to regulate the antigen receptor signaling and cell polarity in lymphocytes; however, the physiological function of Dlg1 in humoral responses is not completely clear. Here, we addressed this question using a conditional knockout (KO) mouse model with Dlg1 deficiency in different B-cell subsets by crossing dlg1fl/fl mice with either mb1cre/+ or aicdacre/+ mice, respectively. In both mouse models, we observed that Dlg1 deficiency in B cells (Dlg1-KO B cells) led to obvious hyper-antibody responses upon immunization, the effect of which was more obvious in antigen-recall responses. Mechanistically, we found that Dlg1-KO B cells exhibited hyper-proliferation compared with wild-type B cells upon antigen stimulation, suggesting that the hyper-antibody responses are likely induced by the hyper-proliferation of Dlg1-KO B cells. Indeed, further studies demonstrated that Dlg1 deficiency in B cells led to the down-regulation of a tumor suppressor, FoxO1. Thus, all these results reveal an unexpected function of Dlg1 in restraining hyper-antibody responses through the inhibition of FoxO1 and thus antigen-binding-induced proliferation in B cells.

Triplet Male Lambs Are More Susceptible than Twins to Dietary Soybean Oil-Induced Fatty Liver.

BACKGROUND: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. OBJECTIVES: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. METHODS: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). RESULTS: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). CONCLUSIONS: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.

Outcomes of Multimodality In situ Recanalization in Hybrid Operating Room (MIRHOR) for symptomatic chronic internal carotid artery occlusions.

BACKGROUND: An in situ recanalization procedure of endovascular therapy (ET) or carotid endarterectomy (CEA) has been attempted in patients with symptomatic chronic internal carotid artery occlusions (ICAOs), though the recanalization rates of both are low. OBJECTIVE: To investigate the outcomes of Multimodality In situ Recanalization for ICAOs in a Hybrid Operating Room (MIRHOR) at the same session. METHODS: Symptomatic chronic ICAOs were classified into type A or B (short occlusion with or without a tapered residual root [TRR]), and C or D (long occlusion with or without TRR), and managed in a hybrid operating room with ET, CEA, or both, as needed. Primary efficacy outcome was technical success of recanalization with Thrombolysis in Myocardial Infarction 3. Secondary efficacy outcome was any stroke or death within 30 days (primary safety outcome) plus an ipsilateral ischemic stroke after 30 days. RESULTS: Technical success was finally achieved in 35 (83.3%) of 42 consecutively enrolled patients with ICAO, which was significantly higher than 35.7% (15/42, p<0.001) from the initial ET or CEA alone. Furthermore, the success rate was in descending order: 100% (18/18) for type A and B occlusions, 75% (6/8) for type C occlusions, and 69% (11/16) for type D occlusions (p=0.017). Two secondary efficacy outcome events (5.1%) without mortality, including one (2.4%) primary safety outcome, were observed during a mean follow-up of 10.5 months. CONCLUSION: The MIRHOR for symptomatic chronic ICAOs at the same session significantly improves technical success, with low periprocedural complications and favorable clinical outcomes. The ICAO classification appears valuable in predicting technical success.

RETRACTED: Downregulation of miR-204 expression correlates with poor clinical outcome of glioma patients.

Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small noncoding RNAs, play an important role in carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in nontumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization grades III and IV versus grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher World Health Organization grade, larger tumor, and worse Karnofsky performance score. Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival and overall survival than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of overall survival and progression-free survival. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer.

Cerebral Syphilitic Gumma Misdiagnosed as a Malignant Brain Tumor.

Syphilitic gumma involvement of the central nervous system is extremely rare and frequently misdiagnosed. The authors report a patient of a cerebral syphilitic gumma resembling a malignant brain tumor in a 62-year-old male. He was first suspected of a malignant brain tumor, but the pathological diagnosis was cerebral syphilitic gumma. This patient with unusual findings illustrates the clinical manifestations, imaging, and therapeutic aspects of cerebral syphilitic gumma.

Racemic oleracein E increases the survival rate and attenuates memory impairment in D-galactose/NaNO2-induced senescent mice.

BACKGROUND: Compounds that possess a pyrrolidone skeleton are a rich resource for the discovery of nootropic drugs. Oleracein E (OE), which possesses both tetrahydroisoquinoline and pyrrolidone skeletons, was first isolated from the medicinal plant Portulaca oleracea L. and was thought to be an active component in the cognition-improvement effect induced by this herb. The aim of this study was to investigate the effect of OE on cognitive impairment in senescent mice and its underlying mechanism of action. METHOD: Senescent Kunming mice were established by the intraperitoneal injection of D-galactose (D-gal, 1250 mg/kg/d) and NaNO2 (90 mg/kg/d) for 8 weeks. OE (3 mg/kg/d, 15 mg/kg/d) was orally administered for 8 weeks, and the nootropic drug piracetam (PA, 400 mg/kg/d) was used as a positive control. A Morris water maze was used to assess cognitive ability. GSH and MDA levels and T-AOC, SOD, and CAT activities in the brain or plasma were determined. Hippocampal morphology was observed by HE staining, and expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic proteins Bax and Caspase-3 was observed by immunohistochemical staining. RESULTS: Large-dosage treatments with D-gal/NaNO2 for 8 weeks significantly reduced survival, impaired spatial memory capacity, compensatorily up-regulated GSH level and T-AOC and SOD activities, decreased CAT activity, and induced hippocampal neuronal damage and apoptosis as reflected by the apparent low expression of Bcl-2 and high expression of Bax and Caspase-3. OE significantly prolonged lifespan and was more potent than PA. Similar to PA, OE at 15 mg/kg/d improved memory capacity. The underlying mechanism of action was related to the reversal of abnormal brain antioxidant biomarkers (GSH, T-AOC, and SOD) to normal levels and the inhibition of hippocampal neuronal apoptosis. CONCLUSION: OE from P. oleracea is an active compound for improving cognitive function and is also a candidate nootropic drug for the treatment of age-related dementia.

Absorption of sulfur dioxide from simulated flue gas by polyethyleneimine-phosphoric acid solution.

Clean fuel technologies have been widely developed in current society because fuel combustion can directly bring about the emission of hazardous gasses such as SO2. Flue gas desulfurization by polyethyleneimine (PEI)-phosphoric acid solution is an efficient desulfurization method. In this research, the PEI and the additive H3PO4 were used as absorption solution. SO2 was absorbed by the system and desorbed from the loaded solution. The cycle operation was also analyzed. Some technology conditions such as the concentration of PEI, the temperature, the gas flow rate, the concentration of SO2 and the pH value were experimentally researched. With the optimized process, the absorption efficiency of this system could reach 98% and the desorption efficiency was over 60%, showing good absorption/desorption capability. With this efficient approach, the present study may open a new window for developing high-performance absorbents which can make SO2 be well desorbed from the loaded solution and better reused in the flue gas desulfurization.

A phenylalanine clamp controls substrate specificity in the quorum-quenching metallo-γ-lactonase from Bacillus thuringiensis.

Autoinducer inactivator A (AiiA) is a metal-dependent N-acyl homoserine lactone hydrolase that displays broad substrate specificity but shows a preference for substrates with long N-acyl substitutions. Previously, crystal structures of AiiA in complex with the ring-opened product N-hexanoyl-l-homoserine revealed binding interactions near the metal center but did not identify a binding pocket for the N-acyl chains of longer substrates. Here we report the crystal structure of an AiiA mutant, F107W, determined in the presence and absence of N-decanoyl-l-homoserine. F107 is located in a hydrophobic cavity adjacent to the previously identified ligand binding pocket, and the F107W mutation results in the formation of an unexpected interaction with the ring-opened product. Notably, the structure reveals a previously unidentified hydrophobic binding pocket for the substrate's N-acyl chain. Two aromatic residues, F64 and F68, form a hydrophobic clamp, centered around the seventh carbon in the product-bound structure's decanoyl chain, making an interaction that would also be available for longer substrates, but not for shorter substrates. Steady-state kinetics using substrates of various lengths with AiiA bearing mutations at the hydrophobic clamp, including insertion of a redox-sensitive cysteine pair, confirms the importance of this hydrophobic feature for substrate preference. Identifying the specificity determinants of AiiA will aid the development of more selective quorum-quenching enzymes as tools and as potential therapeutics.

The kinetic mechanism of S. pneumoniae DNA ligase and inhibition by adenosine-based antibacterial compounds.

The NAD-dependent DNA ligase is an excellent target for the discovery of antibacterial agents with a novel mode of action. In this work the DNA ligase from Streptococcus pneumoniae was investigated for its steady-state kinetic parameters and inhibition by compounds with an adenosine substructure. Inhibition by substrate DNA that was observed in the enzyme turnover experiments was verified by direct binding measurements using isothermal titration calorimetry (ITC). The substrate-inhibited enzyme form was identified as deadenylated DNA ligase. The binding potencies of 2-(butylsulfanyl) adenosine and 2-(cyclopentyloxy) adenosine were not significantly affected by the presence of the enzyme-bound DNA substrate. Finally, a mutant protein was prepared that was known to confer resistance to the adenosine compounds' antibacterial activity. The mutant protein was shown to have little catalytic impairment yet it was less susceptible to adenosine compound inhibition.

Aberrant expression of N-methylpurine-DNA glycosylase influences patient survival in malignant gliomas.

AIM: To examine the expression of N-methylpurine-DNA glycosylase (MPG) gene and protein in glioma samples with different WHO grades and its association with patients' survival. METHODS: Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues. RESULTS: MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). Immunohistochemistry also showed that MPG protein was over-expressed in glioma tissues, which was consistent with the resutls of Western blot analysis. Additionally, the expression levels of MPG gene and protein both increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry and western blot analysis. Moreover, the survival rate of MPG-positive patients was significantly lower than that of MPG-negative patients (P < 0.001). We further confirmed that the over-expression of MPG was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001). CONCLUSIONS: Our data showed the over-expression of MPG gene and protein in human gliomas, and also suggested for the first time that MPG be an unfavorable independent prognostic indicator for glioma patients.