Lung cancer mortality of residents living near petrochemical industrial complexes: a meta-analysis

Background: Lung cancer, as the leading cause of cancer mortality worldwide, has been linked to environmental factors, such as air pollution. Residential exposure to petrochemicals is considered a possible cause of lung cancer for the nearby population, but results are inconsistent across previous studies. Therefore, we performed a meta-analysis to estimate the pooled risk and to identify possible factors leading to the heterogeneity among studies. Methods: The standard process of selecting studies followed the Cochrane meta-analysis guideline of identification, screening, eligibility, and inclusion. We assessed the quality of selected studies using the Newcastle-Ottawa scale. Reported point estimates and 95% confidence intervals were extracted or calculated to estimate the pooled risk. Air quality standards were summarized and treated as a surrogate of exposure to air pollution in the studied countries. Funnel plots, Begg’s test and Egger’s test were conducted to diagnose publication bias. Meta-regressions were performed to identify explanatory variables of heterogeneity across studies. Results: A total of 2,017,365 people living nearby petrochemical industrial complexes (PICs) from 13 independent studied population were included in the analysis. The pooled risk of lung cancer mortality for residents living nearby PICs was 1.03-fold higher than people living in non-PIC areas (95% CI = 0.98–1.09), with a low heterogeneity among studies (I 2 = 25.3%). Such effect was stronger by a factor of 12.6% for the year of follow-up started 1 year earlier (p-value = 0.034). Conclusions: Our meta-analysis gathering current evidence suggests only a slightly higher risk of lung cancer mortality among residents living nearby PICs, albeit such association didn’t receive statistically significance. Reasons for higher risks of early residential exposure to PICs might be attributable to the lack of or less stringent air pollution regulations. Electronic supplementary material The online version of this article (10.1186/s12940-017-0309-2) contains supplementary material, which is available to authorized users

IDENTIFIKASI JIWA KEWIRAUSAHAAN PADA PEMILIK MAFASARI FURNITURE BERDASARKAN TEORI MEREDITH

Penelitian ini berjudul : “IDENTIFIKASI JIWA KEWIRAUSAHAAN PADA PEMILIK MAFASARI FURNITURE BERDASARKAN TEORI MEREDITH” dengan perumusan masalah yaitu bagaimana identifikasi jiwa kewirausahaan pada pemilik MAFASARI furniture berdasarkan teori Meredith ?. Adapun yang menjadi tujuan penelitian ini adalah untuk mengidentifikasi jiwa kewirausahaaan pemilik MAFASARI furniture, berdasarkan teori yang dikemukakan oleh Meredith. Dari hasil identifikasi yang telah didapat, yaitu pemilik MAFASARI furniture memiliki jiwa kewirausahaan yang sesuai dengan teori Meredith, dimana terdapat 6 variabel didalam teori tersebut, yaitu percaya diri, berorientasikan tugas dan hasil, berani mengambil risiko, kepemimpinan, keorisinilan, dan berorientasi ke masa depan. Dari ke-enam variabel tersebut, seluruhnya telah dipenuhi oleh Bapak Slamet Raharjo selaku pemilik dari MAFASARI furniture. Metode pengumpulan data yang digunakan dalam penelitian ini adalah dengan menggunakan metode wawancara

NF-κB1 Inhibits TLR-Induced IFN-β Production in Macrophages Through TPL-2-dependent ERK Activation

available in PMC 2012 February 15.Although NF-κB1 p50/p105 has critical roles in immunity, the mechanism by which NF-κB1 regulates inflammatory responses is unclear. In this study, we analyzed the gene expression profile of LPS-stimulated Nfkb1−/− macrophages that lack both p50 and p105. Deficiency of p50/p105 selectively increased the expression of IFN-responsive genes, which correlated with increased IFN-β expression and STAT1 phosphorylation. IFN Ab-blocking experiments indicated that increased STAT1 phosphorylation and expression of IFN-responsive genes observed in the absence of p50/p105 depended upon autocrine IFN-β production. Markedly higher serum levels of IFN-β were observed in Nfkb1−/− mice than in wild-type mice following LPS injection, demonstrating that Nfkb1 inhibits IFN-β production under physiological conditions. TPL-2, a mitogen-activated protein kinase kinase kinase stabilized by association with the C-terminal ankyrin repeat domain of p105, negatively regulates LPS-induced IFN-β production by macrophages via activation of ERK MAPK. Retroviral expression of TPL-2 in Nfkb1−/− macrophages, which are deficient in endogenous TPL-2, reduced LPS-induced IFN-β secretion. Expression of the C-terminal ankyrin repeat domain of p105 in Nfkb1−/− macrophages, which rescued LPS activation of ERK, also inhibited IFN-β expression. These data indicate that p50/p105 negatively regulates LPS-induced IFN signaling in macrophages by stabilizing TPL-2, thereby facilitating activation of ERK.National Institutes of Health (U.S.) (NIH AI52267)National Institutes of Health (U.S.) (NIH CA108854)National Institutes of Health (U.S.) (NIH CA67529)Medical Research Council (Great Britain

Establishment of a Knock-In Mouse Model with the SLC26A4 c.919-2A>G Mutation and Characterization of Its Pathology

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4tm1Dontuh/tm1Dontuh mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4−/− mice and Slc26a4loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains

Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and Hb

Cbl negatively regulates nlrp3 inflammasome activation through glut1-dependent glycolysis inhibition

Activation of the nod-like receptor 3 (NLRP3) inflammasomes is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Cbl plays a pivotal role in suppressing NLRP3 inflammasome activation by inhibiting Pyk2-mediated apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Here, we showed that Cbl dampened NLRP3 inflammasome activation by inhibiting glycolysis, as demonstrated with Cbl knockout cells and treatment with the Cbl inhibitor hydrocotarnine. We revealed that the inhibition of Cbl promoted caspase-1 cleavage and interleukin (IL)-1β secretion through a glycolysis-dependent mechanism. Inhibiting Cbl increased cellular glucose uptake, glycolytic capacity, and mitochondrial oxidative phosphorylation capacity. Upon NLRP3 inflammasome activation, inhibiting Cbl increased glycolysis-dependent activation of mitochondrial respiration and increased the production of reactive oxygen species, which contributes to NLRP3 inflammasome activation and IL-1β secretion. Mechanistically, inhibiting Cbl increased surface expression of glucose transporter 1 (GLUT1) protein through post-transcriptional regulation, which increased cellular glucose uptake and consequently raised glycolytic capacity, and in turn enhanced NLRP3 inflammasome activation. Together, our findings provide new insights into the role of Cbl in NLRP3 inflammasome regulation through GLUT1 downregulation. We also show that a novel Cbl inhibitor, hydrocortanine, increased NLRP3 inflammasome activity via its effect on glycolysis

A delta-doped quantum well system with additional modulation doping

A delta-doped quantum well with additional modulation doping may have potential applications. Utilizing such a hybrid system, it is possible to experimentally realize an extremely high two-dimensional electron gas (2DEG) density without suffering inter-electronic-subband scattering. In this article, the authors report on transport measurements on a delta-doped quantum well system with extra modulation doping. We have observed a 0-10 direct insulator-quantum Hall (I-QH) transition where the numbers 0 and 10 correspond to the insulator and Landau level filling factor ν = 10 QH state, respectively. In situ titled-magnetic field measurements reveal that the observed direct I-QH transition depends on the magnetic component perpendicular to the quantum well, and the electron system within this structure is 2D in nature. Furthermore, transport measurements on the 2DEG of this study show that carrier density, resistance and mobility are approximately temperature (T)-independent over a wide range of T. Such results could be an advantage for applications in T-insensitive devices

Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag