The c-Jun NH2-terminal kinase (JNK) pathway represents one subgroup of MAP kinases that are activated primarily by cytokines and exposure to environmental stress. Autophagy is a protein-degradation ...system characterized by the formation of double-membrane vacuoles termed autophagosomes. Autophagy-related gene beclin 1 plays a key role in autophagosome formation. However, the relationships between activation of JNK pathway, autophagy induction and Beclin 1 expression remain elusive. In this study, we used human cancer cell lines CNE2 and Hep3B to investigate the role of JNK-mediated Beclin 1 expression in ceramide-induced autophagic cell death. Ceramide-treated cells exhibited the characteristics of autophagy (that is, acidic vesicular organelle formation and the LC3-II generation). JNK was activated in these two cell lines exposed to ceramide and the phosphorylation of c-Jun also increased. In the meantime, we found that ceramide upregulated Beclin 1 expression in cancer cells. The upregulation of Beclin 1 expression could be blocked by SP600125 (a specific inhibitor of JNK) or a small interfering RNA (siRNA) directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase reporter analysis revealed that c-Jun was involved in the regulation of beclin 1 transcription in response to ceramide treatment. In addition, inhibition of JNK activity by SP600125 could inhibit autophagy induction by ceramide. Furthermore, Beclin 1 knockdown by siRNA also inhibited ceramide-mediated autophagic cell death. JNK-mediated Beclin 1 expression was also observed in topotecan-induced autophagy. These data suggest that activation of JNK pathway can mediate Beclin 1 expression, which plays a key role in autophagic cell death in cancer cells.
The prevalence of diabetes in China is among the highest in the world. For this reason, findings from the 2016 Global Burden of Disease (GBD) study were used to calculate the burden of hyperglycaemia ...and diabetes in China.
Following the general analytical strategy used in GBD 2016, diabetes prevalence and mortality were analyzed by age and gender. Trends in disability-adjusted life years (DALYs) due to diabetes were assessed in 33 province-level administrative units from 1990 to 2016, and similar data were provided for chronic kidney disease (CKD) related to diabetes and, as an overall summarizing measure, for hyperglycaemia expressed as high fasting plasma glucose (HFPG).
From 1990 to 2016, all-age prevalence of diabetes rose from 3.7% to 6.6%, and all-age diabetes and diabetes-related CKD mortality rates increased by 63.5% and 33.3%, respectively, with both rates increasing more rapidly in diabetes patients aged 15–49 years than in any other age groups. In 2016, HFPG became China's sixth leading cause of DALYs, and the attributable DALYs burden was 1802.3/100,000 population. Although the number of diabetes DALYs increased by 95% from 1990 to 2016, age-standardized diabetes DALYs rates increased by only 2.3%. Also, from 1990 to 2016, rates of age-standardized DALYs due to diabetes decreased in 14 provinces, but increased in 19 provinces. High BMI Scores and diets low in whole grains, nuts and seeds were the most important risk factors for diabetes in 2016.
Diabetes and hyperglycaemia constitute a huge health burden in China. The substantial increase in diabetes-related burden represents an ongoing challenge, given the rapidly ageing Chinese population. Thus, a targeted control and preventative strategy needs to be developed at risk factor level to reduce this burden.
The Pearl River Delta (PRD) region in southeastern China is one of the most polluted industrial and metropolitan areas in the world. We report single‐particle measurements of the refractory black ...carbon (rBC) component in ambient aerosol in the region, and we interpret the results to improve understanding of the importance of rBC for radiative forcing in this region and others like it. A Single‐Particle Soot Photometer (SP2) provided rBC mass loadings, size distributions, and mixing state information. Average rBC loadings are approximately an order of magnitude higher than those measured near Houston, Texas, a major U.S. metropolitan area. The rBC in the PRD is also more often internally mixed with nonrefractory materials than is rBC around Houston. Localized atmospheric heating from rBC solar absorption reached an average rate of 0.4 K d−1. A one‐dimensional discrete ordinates radiative transfer (DISORT) model coupled with the average measured rBC is used to illustrate the potential local contribution of rBC mass and associated scattering aerosol to the radiative forcing. Solar energy deposition rates in the atmosphere at the sampling site due to rBC absorption are estimated to have an average value of 17 W m−2 and be largest in the first 1 km above the ground. These results indicate that rBC has significant potential to influence local meteorology and climate parameters in the PRD region.
Key Points
We performed black carbon measurements in China
A single‐particle soot photometer was used to determine black carbon properties
Solar energy deposition rates due to the black carbon were estimated
We experimentally study the coupling of group V donor spins in silicon to mechanical strain, and measure strain-induced frequency shifts that are linear in strain, in contrast to the quadratic ...dependence predicted by the valley repopulation model (VRM), and therefore orders of magnitude greater than that predicted by the VRM for small strains |ϵ|<10^{-5}. Through both tight-binding and first principles calculations we find that these shifts arise from a linear tuning of the donor hyperfine interaction term by the hydrostatic component of strain and achieve semiquantitative agreement with the experimental values. Our results provide a framework for making quantitative predictions of donor spins in silicon nanostructures, such as those being used to develop silicon-based quantum processors and memories. The strong spin-strain coupling we measure (up to 150 GHz per strain, for Bi donors in Si) offers a method for donor spin tuning-shifting Bi donor electron spins by over a linewidth with a hydrostatic strain of order 10^{-6}-as well as opportunities for coupling to mechanical resonators.
Complex-oxide materials exhibit physical properties that involve the interplay of charge and spin degrees of freedom. However, an ambipolar oxide that is able to exhibit both electron-doped and ...hole-doped ferromagnetism in the same material has proved elusive. Here we report ambipolar ferromagnetism in LaMnO
, with electron-hole asymmetry of the ferromagnetic order. Starting from an undoped atomically thin LaMnO
film, we electrostatically dope the material with electrons or holes according to the polarity of a voltage applied across an ionic liquid gate. Magnetotransport characterization reveals that an increase of either electron-doping or hole-doping induced ferromagnetic order in this antiferromagnetic compound, and leads to an insulator-to-metal transition with colossal magnetoresistance showing electron-hole asymmetry. These findings are supported by density functional theory calculations, showing that strengthening of the inter-plane ferromagnetic exchange interaction is the origin of the ambipolar ferromagnetism. The result raises the prospect of exploiting ambipolar magnetic functionality in strongly correlated electron systems.
Background
Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular ...endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis.
Methods
The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated.
Results
Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (
P
= 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (
P
= 0.001) and overall survival, OS (
P
= 0.011).
Conclusions
Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.
To evaluate the association between pre‐natal and post‐natal exposure to pet ownership and lung function in children, a cross‐sectional study named Seven Northeastern Cities (SNEC) study was ...conducted. In this study, children's lung function including the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal mid‐expiratory flow (MMEF), and peak expiratory flow (PEF) were measured by spirometers, and pet ownership situations were collected by questionnaire. Analyzed by multiple logistic regression and generalized linear modeling, we found that for all subjects, pet exposure in the first 2 years of life was significantly associated with lung function impairment of FVC<85% predicted (adjusted odds ratio aOR=1.28; 95% confidence interval CI: 1.01, 1.63). For current pet exposure, the increased odds of lung function impairment ranged from 35% (aOR=1.35; 95%CI: 1.12, 1.62) for FVC<85% predicted to 57% (aOR=1.57; 95%CI: 1.29, 1.93) for FEV1<85% predicted. The in utero exposure was not related to lung function impairment. Compared with other pets, higher odds were observed among children with dogs. When stratified by gender, girls with current pet exposure were more likely to have lung function impairment than boys. It implies self‐reported exposures to pets were negatively associated with lung function among the children under study.
We have analysed time-slice simulations from 17 global models, participating in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), to explore changes in present-day (2000) ...hydroxyl radical (OH) concentration and methane (CH4) lifetime relative to preindustrial times (1850) and to 1980. A comparison of modeled and observation-derived methane and methyl chloroform lifetimes suggests that the present-day global multi-model mean OH concentration is overestimated by 5 to 10% but is within the range of uncertainties. The models consistently simulate higher OH concentrations in the Northern Hemisphere (NH) compared with the Southern Hemisphere (SH) for the present-day (2000; inter-hemispheric ratios of 1.13 to 1.42), in contrast to observation-based approaches which generally indicate higher OH in the SH although uncertainties are large. Evaluation of simulated carbon monoxide (CO) concentrations, the primary sink for OH, against ground-based and satellite observations suggests low biases in the NH that may contribute to the high north–south OH asymmetry in the models. The models vary widely in their regional distribution of present-day OH concentrations (up to 34%). Despite large regional changes, the multi-model global mean (mass-weighted) OH concentration changes little over the past 150 yr, due to concurrent increases in factors that enhance OH (humidity, tropospheric ozone, nitrogen oxide (NOx) emissions, and UV radiation due to decreases in stratospheric ozone), compensated by increases in OH sinks (methane abundance, carbon monoxide and non-methane volatile organic carbon (NMVOC) emissions). The large inter-model diversity in the sign and magnitude of preindustrial to present-day OH changes (ranging from a decrease of 12.7% to an increase of 14.6%) indicate that uncertainty remains in our understanding of the long-term trends in OH and methane lifetime. We show that this diversity is largely explained by the different ratio of the change in global mean tropospheric CO and NOx burdens (Delta CO/Delta NOx, approximately represents changes in OH sinks versus changes in OH sources) in the models, pointing to a need for better constraints on natural precursor emissions and on the chemical mechanisms in the current generation of chemistry-climate models. For the 1980 to 2000 period, we find that climate warming and a slight increase in mean OH (3.5 +/- 2.2%) leads to a 4.3 +/- 1.9% decrease in the methane lifetime. Analysing sensitivity simulations performed by 10 models, we find that preindustrial to present-day climate change decreased the methane lifetime by about four months, representing a negative feedback on the climate system. Further, we analysed attribution experiments performed by a subset of models relative to 2000 conditions with only one precursor at a time set to 1860 levels. We find that global mean OH increased by 46.4 +/- 12.2% in response to preindustrial to present-day anthropogenic NOx emission increases, and decreased by 17.3 +/-2.3%, 7.6 +/- 1.5%, and 3.1 +/- 3.0% due to methane burden, and anthropogenic CO, and NMVOC emissions increases, respectively.
To evaluate the diagnostic performance of 2-18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in TA diagnosis and Takayasu arteritis (TA) activity ...assessment.
This retrospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria and undergoing 18F-FDG PET/CT imaging from October 2010 to July 2022. TA activity was assessed through 18F-FDG PET/CT (maximum standard uptake value SUVmax, vascular SUVmax/mean standard uptake value SUVmean of liver (SUV ratio), and PET vascular activity score PETVAS) using physician global assessment (PGA) as the reference standard, and the results of these assessments were compared against the clinical activity scores (National Institutes of Health NIH and Indian Aortitis Disease Activity ITAS-A scores), acute-phase reactants (APR), and white blood cell and platelet counts.
Twenty 18F-FDG PET/CT examinations from 19 patients were included in the study, nine were performed in the active phase and 11 in the inactive phase. The involved vessels showed segmental and tubular FDG uptake in the active group. The average SUVmax, SUV ratio, and PETVAS was 6.3 ± 2.7 (range 3.4–12), 4.2 ± 1.7 (range 2.1–7.5), and 22.7 ± 11.2 (range 6–39), respectively, in the active group and 1.7 ± 0.9 (0.9–3.1), 1.1 ± 0.6 (range 0.6–2.4), and 3.5 ± 5.5 (range 0–18), respectively, in the inactive group. The sensitivity, specificity of SUVmax, SUV ratio, and PETVAS for TA activity assessment were 100%, 100%; 100%, 90.9%; and 88.9, 90.9%, respectively. After ROC curve analysis, a new SUVmax cut-off was obtained. Based on the new cut-off value, SUVmax 3.3 and SUV ratio 1.9 had a more perfect assessment performance.
18F-FDG PET/CT is an alternative imaging technique for TA.
•18F-FDG PET/CT has advantages in TAK activity assessment.•Arterial SUVmax and SUV target/background ratio are important parameters for TAK activity assessment.•18F-FDG PET/CT allows for a more accurate classification of TAK.•PET/CT can better evaluate TAK efficacy
Results from simulations performed for the Atmospheric Chemistry and Climate Modeling Intercomparison Project (ACCMIP) are analysed to examine how OH and methane lifetime may change from present day ...to the future, under different climate and emissions scenarios. Present day (2000) mean tropospheric chemical lifetime derived from the ACCMIP multi-model mean is 9.8+/-1.6 yr (9.3+/-0.9 yr when only including selected models), lower than a recent observationally-based estimate, but with a similar range to previous multi-model estimates. Future model projections are based on the four Representative Concentration Pathways (RCPs), and the results also exhibit a large range. Decreases in global methane lifetime of 4.5 +/- 9.1% are simulated for the scenario with lowest radiative forcing by 2100 (RCP 2.6), while increases of 8.5+/-10.4% are simulated for the scenario with highest radiative forcing (RCP 8.5). In this scenario, the key driver of the evolution of OH and methane lifetime is methane itself, since its concentration more than doubles by 2100 and it consumes much of the OH that exists in the troposphere. Stratospheric ozone recovery, which drives tropospheric OH decreases through photolysis modifications, also plays a partial role. In the other scenarios, where methane changes are less drastic, the interplay between various competing drivers leads to smaller and more diverse OH and methane lifetime responses, which are difficult to attribute. For all scenarios, regional OH changes are even more variable, with the most robust feature being the large decreases over the remote oceans in RCP8.5. Through a regression analysis, we suggest that differences in emissions of non-methane volatile organic compounds and in the simulation of photolysis rates may be the main factors causing the differences in simulated present day OH and methane lifetime. Diversity in predicted changes between present day and future OH was found to be associated more strongly with differences in modelled temperature and stratospheric ozone changes. Finally, through perturbation experiments we calculated an OH feedback factor (F) of 1.24 from present day conditions (1.50 from 2100 RCP8.5 conditions) and a climate feedback on methane lifetime of 0.33+-0.13 yr/K, on average. Models that did not include interactive stratospheric ozone effects on photolysis showed a stronger sensitivity to climate, as they did not account for negative effects of climate-driven stratospheric ozone recovery on tropospheric OH, which would have partly offset the overall OH/methane lifetime response to climate change.
PDF
