Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those ...patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFR
) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFR
and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFR
.
Background Fluid overload is a common phenomenon in patients in a late stage of chronic kidney disease (CKD). However, little is known about whether fluid overload is related to kidney disease ...progression in patients with CKD. Accordingly, the aim of the study was to assess the association of the severity of fluid status and kidney disease progression in an advanced CKD cohort. Study Design Prospective observational cohort study. Setting & Participants This cohort study enrolled 472 non−dialysis-dependent patients with CKD stages 4-5 who were in an integrated CKD care program from January 2011 to December 2011 and followed up until December 2012 or initiation of renal replacement therapy (RRT). Predictors Tertile of fluid overload, with cutoff values at 0.6 and 1.6 L. Outcomes RRT, rapid estimated glomerular filtration rate (eGFR) decline (faster than 3 mL/min/1.73 m2 per year), and change in eGFR. Measurements The severity of fluid overload was measured by a bioimpedance spectroscopy method. eGFR was computed using the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. Results During a median 17.3-month follow-up, 71 (15.0%) patients initiated RRT and 187 (39.6%) experienced rapid eGFR decline. The severity of fluid overload was associated with increased risk of RRT (tertile 3 vs tertile 1: adjusted HR, 3.16 95% CI, 1.33-7.50). Fluid overload value was associated with increased risk of rapid eGFR decline (tertile 3 vs tertile 1: adjusted OR, 4.68 95% CI, 2.30-9.52). Furthermore, the linear mixed-effects model showed that the reduction in eGFR over time was faster in tertile 3 than in tertile 1 ( P = 0.02). Limitations The effect of fluid volume variation over time must be considered. Conclusions Fluid overload is an independent risk factor associated with initiation of RRT and rapid eGFR decline in patients with advanced CKD.
Interface carrier recombination currently hinders the performance of hybrid organic–silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate ...1,1-bis(di-4-tolylamino)phenylcyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open-circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics.
A series of donor–acceptor–donor triazine‐based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue‐emitting OLEDs with ...non‐doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color. The introduction of long alkyl chains on the triazine core inhibits the unwanted intermolecular D–D/A–A‐type π–π interactions, resulting in the intermolecular D–A charge transfer. The weak aggregation‐caused quenching (ACQ) effect caused by the suppressed intermolecular D–D/A–A‐type π–π interaction further enhances the emission. The crowded molecular structure allows the electron donor and acceptor to be nearly orthogonal, thereby reducing the energy gap between triplet and singlet excited states (ΔEST). As a result, blue‐emitting devices with TH‐2DMAC and TH‐2DPAC non‐doped EMLs showed satisfactory efficiencies of 12.8 % and 15.8 %, respectively, which is one of the highest external quantum efficiency (EQEs) reported for blue TADF emitters (λpeak<475 nm), demonstrating that our tailored molecular designs are promising strategies to endow OLEDs with excellent electroluminescent performances.
Getting the blues: A series of donor–acceptor–donor triazine‐based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue‐emitting OLEDs with non‐doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color.
is a fungus used to ferment tempeh in Indonesia and is generally recognized as safe (GRAS) for human consumption by the USA FDA. We previously assessed the effect of a tempeh extract on cortisol ...levels in zebrafish but did not include behavioral studies. Here, we measured the GABA content in three strains of
, two isolated by us (MHU 001 and MHU 002) and one purchased. We then investigated the effect of tempeh on cortisol and the gut microbiota in a zebrafish experimental model. GABA concentration was the highest in MHU 002 (9.712 ± 0.404 g kg
) followed by our MHU 001 strain and the purchased one. The fish were divided into one control group fed a normal diet and three experimental groups fed soybean tempeh fermented with one of the three strains of
. After two weeks, individual fish were subjected to unpredicted chronic stress using the novel tank diving test and the tank light-dark test. Next-generation sequencing was used to analyze gut microbial communities and RT-PCR to analyze the expression of BDNF (brain-derived neurotrophic factor) gene and of other genes involved in serotonin signaling/metabolism in gut and brain. Tempeh-fed zebrafish exhibited increased exploratory behavior (less stress) in both tank tests. They also had significantly reduced gut Proteobacteria (include
) (51.90% vs. 84.97%) and significantly increased gut Actinobacteria (include
spp.) (1.80% vs. 0.79%). The content of
, a "psychobiotic", increased ten-fold from 0.04% to 0.45%. Tempeh also increases BDNF levels in zebrafish brain.
MHU 001 greatly improved the anti-stress effect of tempeh and microbiota composition in zebrafish gut.
Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with ...non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio aHR, 2.73; 95% confidence interval 95% CI, 2.62-2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91-3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74-2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77-2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Iron deficiency (ID) and iron deficiency anemia (IDA) typically occur in developing countries. Notably, ID and IDA can affect an infant's emotion, cognition, and development. Breast milk is ...considered the best food for infants. However, recent studies have indicated that breastfeeding for more than six months increases the risk of ID. This study investigated the prevalence of ID and IDA, as well as the association between feeding type and iron nutritional status in northern Taiwan. A cross-sectional study was conducted on infants who returned to the well-baby clinic for routine examination from October 2012 to January 2014. Overall, 509 infants aged 1-12 months completed the iron nutritional status analysis, anthropometric measurement, and dietary intake assessment, including milk and complementary foods. The results revealed that 49 (10%) and 21 (4%) infants in their first year of life had ID and IDA, respectively, based on the World Health Organization criteria. Breastfed infants had a higher prevalence rate of ID and IDA than mixed-fed and formula-fed infants (
< 0.001). Regarding biomarkers of iron status, plasma hemoglobin (Hb), ferritin, and transferrin saturation (%) levels were significantly lower in ID and IDA groups. The prevalence of ID and IDA were 3.7% and 2.7%, respectively, in infants under six months of age, but increased to 20.4% and 6.6%, respectively, in infants above six months of age. The healthy group had a higher total iron intake than ID and IDA groups, mainly derived from infant formula. The total dietary iron intake was positively correlated with infants' Hb levels. Compared with formula-fed infants, the logistic regression revealed that the odds ratio for ID was 2.157 (95% confidence interval CI: 1.369-3.399) and that for IDA was 4.196 (95% CI: 1.780-9.887) among breastfed infants (
< 0.001) after adjusted for all confounding factors (including gestational week, birthweight, sex, body weight percentile, body length percentile, age of infants, mothers' BMI, gestational weight gain, education level, and hemoglobin level before delivery). In conclusion, our results determined that breastfeeding was associated with an increased the prevalence of ID and/or IDA, especially in infants above six months. This suggests that mothers who prolonged breastfeed after six months could provide high-quality iron-rich foods to reduce the prevalence of ID and IDA.
To elucidate the accuracy, efficacy, and safety of percutaneous iliosacral screw (ISS) and trans-iliac trans-sacral screw (TITS) insertion using a single C-arm fluoroscopy intensifier. Additionally, ...the potential risk factors that might cause mal-positioned screws were identified. Patients with pelvic ring injuries who underwent percutaneous screw fixation in a single medical institute were divided into an ISS group (n = 59) and a TITS group (n = 62) and assessed. The angles deviated from ideal orientation (ADIO) of the implanted screw were measured, and potential risk factors for mal-positioned screws were analyzed. Overall, the reduction quality of the pelvic ring was good or excellent in 70 patients (82.4%) by Matta's criteria and in 48 patients (56.5%) by Lefaivre's criteria. ADIO measurements of the ISS and TITS groups via multi-planar computed tomography were 9.16° ± 6.97° and 3.09° ± 2.8° in the axial view, respectively, and 5.92° ± 3.65° and 2.10° ± 2.01° in the coronal view, respectively. Univariate statistical analysis revealed body mass index as the single potential risk factor of mal-positioned screws. With careful preoperative planning and intraoperative preparations, placing ISS and TITS under the guidance of single C-arm fluoroscopy intensifier is a reliable and safe technique. Caution should be exercised when performing this procedure in patients with a high body mass index.
Reversal of promoter DNA hypermethylation and associated gene silencing is an attractive cancer therapy approach. The DNA methylation inhibitors decitabine and azacitidine are efficacious for ...hematological neoplasms at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, which do not explain the prolonged time to response observed in patients. We show that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses, without causing immediate cytotoxicity, produce an antitumor “memory” response, including inhibition of subpopulations of cancer stem-like cells. These effects are accompanied by sustained decreases in genomewide promoter DNA methylation, gene reexpression, and antitumor changes in key cellular regulatory pathways. Low-dose decitabine and azacitidine may have broad applicability for cancer management.
► Transient DAC or AZA sustains antitumor responses and reduces self-renewal ► Acute cytotoxicity does not appear to account for the lasting effects of the drugs ► Low-dose DAC causes sustained global DNA demethylation and gene reexpression ► Low-dose DAC or AZA sustains antitumor responses through key signaling pathways
PDF
