Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: A potential target for prognosis and immune response

Background: It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified. Method: Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation. Results: PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment. Conclusions: This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.</p

Acclimation of photosystem II to high temperature in two Wedelia species from different geographical origins: implications for biological invasions upon global warming

More intense, more frequent, and longer heat waves are expected in the future due to global warming, which could have dramatic ecological impacts. However, few studies have involved invasive species. The aims of this study were to examine the effect of extreme heating (40/35°C for 30d) on the growth and photosynthesis of an alien invasive species Wedelia trilobata and its indigenous congener (Wedelia chinensis) in South China, and to determine the development of this invasive species and its potential adaptive mechanism. In comparison with W. chinensis, W. trilobata suffered less inhibition of the relative growth rate (RGR) and biomass production due to high temperature, which was consistent with the changes of photosystem II (PSII) activity and net photosynthetic rate (Pn). High temperature caused a partial inhibition of PSII, but the adverse effect was more severe in W. chinensis. Measurement of the minimum fluorescence (Fo) versus temperature curves showed that W. trilobata had a higher inflexion temperature of Fo (Ti), indicating greater thermostability of the photosynthetic apparatus. Moreover, comparisons of absorbed light energy partitioning revealed that W. trilobata increased xanthophyll-dependent thermal dissipation (ΦNPQ) under high temperature, while retaining the higher fraction of absorbed light allocated to photochemistry (ΦPSII) relative to W. chinensis. The results suggest that the invasive W. trilobata has a high thermostability of its photosynthetic apparatus and an effective regulating mechanism in energy partitioning of PSII complexes to minimize potential damage and to retain greater capability for carbon assimilation. These factors confer greater heat stress tolerance compared with the native species. Therefore, the invasive W. trilobata may become more aggressive with the increasingly extreme heat climates

Does eco-innovation and green investment limit the CO2 emissions in China?

The continuous upsurge in worldwide economic development and human activities has intensified CO2 emissions that highlighted the significant role of eco-innovation and green investment in curbing CO2 emissions. The study aims to explore the impact of eco-innovation and green investment on CO2 emissions by using the China dataset for time period 1990–2019. The study adopts the ARDL approach. The study used two proxies to determine the impact of eco-innovation, namely environment-related technologies and patents. The empirical estimates of the ARDL approach confirm the negative impact of eco-innovation and green investment on CO2 emissions confirming that these determinants result in limiting CO2 emissions in China. Based on these findings, the study suggests strengthening environmentally friendly policies and the advancement of green investment to mitigate CO2 emissions

Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model

BACKGROUND: Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC. METHODS: Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting. RESULTS: In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated. CONCLUSIONS: iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC

Cluster-randomized, crossover trial of head positioning in acute stroke

The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P\u3c0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P = 0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P = 0.83). There were no significant betweengroup differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours

Fibroblast growth factor (FGF21) protects mouse liver against D-galactose-induced oxidative stress and apoptosis via activating Nrf2 and PI3K/Akt pathways

FGF21 is recently discovered with pleiotropic effects on glucose and lipid metabolism. However, the potential protective effect of FGF21 against D-gal-induced injury in the liver has not been demonstrated. The aim of this study is to investigate the pathophysiological role of FGF21 on hepatic oxidative injury and apoptosis in mice induced by D-gal. The 3-month-old Kunming mice were subcutaneously injected with D-gal (180 mg kg(-1) d(1)) for 8 weeks and administered simultaneously with FGF21 (5 or 1 mg kg(-1) d(1)). Our results showed that the administration of FGF21 significantly alleviated histological lesion including structure damage, degeneration, and necrosis of hepatocytes induced by D-gal, and attenuated the elevation of liver injury markers, serum AST, and ALP in a dosedependent manner. FGF21 treatment also suppressed D-galinduced profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level in the liver, and restored the activities of antioxidant enzymes SOD, CAT, GSH-Px, and T-AOC. Moreover, FGF21 treatment increased the nuclear abundance of Nrf2 and subsequent up regulation of several antioxidant genes. Furthermore, a TUNEL assay showed that D-gal-induced apoptosis in the mouse liver was significantly inhibited by FGF21. The expression of caspase-3 was markedly inhibited by the treatment of FGF21 in the liver of D-gal-treated mice. The levels of PI3K and PBK/Akt were also largely enhanced, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro-and anti-apoptotic Bcl-2 and Bax proteins in the liver of D-gal-treated mice. In conclusion, these results suggest that FGF21 protects the mouse liver against D-gal-induced hepatocyte oxidative stress via enhancing Nrf2-mediated antioxidant capacity and apoptosis via activating PI3K/Akt pathway

Risk factors and prediction model of sleep disturbance in patients with maintenance hemodialysis: A single center study

ObjectivesThis study aimed to explore the risk factors and develop a prediction model of sleep disturbance in maintenance hemodialysis (MHD) patients.MethodsIn this study, 193 MHD patients were enrolled and sleep quality was assessed by Pittsburgh Sleep Quality Index. Binary logistic regression analysis was used to explore the risk factors for sleep disturbance in MHD patients, including demographic, clinical and laboratory parameters, and that a prediction model was developed on the basis of risk factors by two-way stepwise regression. The final prediction model is displayed by nomogram and verified internally by bootstrap resampling procedure.ResultsThe prevalence of sleep disturbance and severe sleep disturbance in MHD patients was 63.73 and 26.42%, respectively. Independent risk factors for sleep disturbance in MHD patients included higher 0.1*age (OR = 1.476, 95% CI: 1.103–1.975, P = 0.009), lower albumin (OR = 0.863, 95% CI: 0.771–0.965, P = 0.010), and lower 10*calcium levels (OR = 0.747, 95% CI: 0.615–0.907, P = 0.003). In addition, higher 0.1*age, lower albumin levels, and anxiety were independently associated with severe sleep disturbance in MHD patients. A risk prediction model of sleep disturbance in MHD patients showed that the concordance index after calibration is 0.736, and the calibration curve is approximately distributed along the reference line.ConclusionsOlder age, lower albumin and calcium levels are higher risk factors of sleep disturbance in MHD, and the prediction model for the assessment of sleep disturbance in MHD patients has excellent discrimination and calibration