Residential Proximity to Major Roadways and Risk of Type 2 Diabetes Mellitus: A Meta-Analysis.

Research indicates that higher levels of traffic-related pollution exposure increase the risk of diabetes, but the association between road proximity and diabetes risk remains unclear. To assess and quantify the association between residential proximity to major roadways and type 2 diabetes, a systematic review and meta-analysis was performed. Embase, Medline, and Web of Science were searched for eligible studies. Using a random-effects meta-analysis, the summary relative risks (RRs) were calculated. Bayesian meta-analysis was also performed. Eight studies (6 cohort and 2 cross-sectional) with 158,576 participants were finally included. The summary unadjusted RR for type 2 diabetes associated with residential proximity to major roadways was 1.24 (95% confidence interval [CI]: 1.07-1.44, p = 0.001, I² = 48.1%). The summary adjusted RR of type 2 diabetes associated with residential proximity to major roadways was 1.12 (95% CI: 1.03-1.22, p = 0.01, I² = 17.9%). After excluding two cross-sectional studies, the summary results suggested that residential proximity to major roadways could increase type 2 diabetes risk (Adjusted RR = 1.13; 95% CI: 1.02-1.27, p = 0.025, I² = 36.6%). Bayesian meta-analysis showed that the unadjusted RR and adjusted RR of type 2 diabetes associated with residential proximity to major roadways were 1.22 (95% credibility interval: 1.06-1.55) and 1.13 (95% credibility interval: 1.01-1.31), respectively. The meta-analysis suggested that residential proximity to major roadways could significantly increase risk of type 2 diabetes, and it is an independent risk factor of type 2 diabetes. More well-designed studies are needed to further strengthen the evidence

Screening and characterization of phenolic compounds by LC-ESI-QTOF-MS/MS and their antioxidant potentials in papaya fruit and their by-products activities

Papaya (Carica papaya L.) is one of the most commonly planted and consumed fruits in the world, especially in tropical and subtropical areas. In recent years, due to the diverse range of nutritional value and medicinal properties of bioactive substances possessed in papaya, papaya fruit and their by-products have gained more attention. The present study aimed to characterize the different parts (pulp, peel, and seed) of two varieties of papaya (yellow- and red-fleshed) at different stages of ripeness (unripe and ripe) for their phenolic compounds using liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS). The phenolic content and antioxidant activity were detected through several assays. Yellow-fleshed unripe papaya seed showed the highest total phenolic content (TPC) (4.73 mg GAE/g). Red-fleshed ripe papaya peel exhibited the highest level of total tannin content (TTC) with 1.98 mg CE/g, while red-fleshed unripe peel exhibited the highest total flavonoid content (TFC) with 2.78 ± 0.04 mg QE/g. In terms of antioxidant potential, yellow-fleshed unripe papaya peels had the highest radical scavenging activities for the DPPH, ABTS, and TAC tests. LC-ESI-QTOF-MS/MS experiment successfully tentatively identified 118 phenolic compounds in total, including phenolic acids (35), flavonoids (61), stilbenes (3), lignans (7) and other polyphenols (12) in all papaya samples. Analyses indicate that the three different parts of the papaya fruit are potential sources of phenolic compounds, particularly the peel. The results of this study provide practical data for the potential application of papaya fruit as a functional food ingredient in the food, pharmaceutical and medicinal industries

Highly active and stable CuAlOx/WO3photoanode for simultaneous pollutant degradation, hydrogen and electricity generation

An unassisted solar water-energy nexus system (SWENS) based on an ultra-thin CuAlOx overlayer coated WO3 nanoplate array (CuAlOx/WO3) photoanode, a rear silicon solar cell and a Pt-black/Pt cathode was proposed to efficiently degrade refractory organic pollutants and simultaneously produce hydrogen and electricity. The formed p-n junction between p-type CuAlOx and n-type WO3 effectively facilitated the charge separation in the CuAlOx/WO3 photoanode. Moreover, the CuAlOx overlayer enhanced the capture of photogenerated holes and isolated WO3 from the solution, thereby improving the charge transfer and inhibiting the photocorrosion of WO3. Therefore, the optimized CuAlOx/WO3 photoanode showed a significantly enhanced and stable photocurrent density of ∼2.82 mA cm-2 at 1.0 V vs. Ag/AgCl, which was ∼4 times higher than that of the pristine WO3. Based on this outstanding photoelectrocatalytic performance, the assembled SWENS showed a degradation efficiency of nearly 100% for tetracycline, a hydrogen generation rate of ∼26.8 μmol·h-1·cm-2 and a power density of ∼593 μW cm-2 under simulated solar light illumination. Our SWENS also exhibited outstanding universality in degrading various refractory organic pollutants for green energy production

Plug-and-Play Shape Refinement Framework for Multi-site and Lifespan Brain Skull Stripping

Skull stripping is a crucial prerequisite step in the analysis of brain magnetic resonance images (MRI). Although many excellent works or tools have been proposed, they suffer from low generalization capability. For instance, the model trained on a dataset with specific imaging parameters cannot be well applied to other datasets with different imaging parameters. Especially, for the lifespan datasets, the model trained on an adult dataset is not applicable to an infant dataset due to the large domain difference. To address this issue, numerous methods have been proposed, where domain adaptation based on feature alignment is the most common. Unfortunately, this method has some inherent shortcomings, which need to be retrained for each new domain and requires concurrent access to the input images of both domains. In this paper, we design a plug-and-play shape refinement (PSR) framework for multi-site and lifespan skull stripping. To deal with the domain shift between multi-site lifespan datasets, we take advantage of the brain shape prior, which is invariant to imaging parameters and ages. Experiments demonstrate that our framework can outperform the state-of-the-art methods on multi-site lifespan datasets.</p

Dual roles of endothelial FGF-2-FGFR1-PDGF-BB and perivascular FGF-2-FGFR2-PDGFRβ signaling pathways in tumor vascular remodeling.

Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRβ signaling for vascular recruitment. FGF-2 sensitizes the PDGFRβ signaling through increasing PDGFRβ levels in pericytes. To ensure activation of PDGFRβ, the FGF-2-FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFRβ, in angiogenic endothelial cells. Thus, FGF-2 directly and indirectly stimulates pericyte proliferation and recruitment by modulating the PDGF-PDGFRβ signaling. Our study identifies a novel mechanism by which the FGF-2 and PDGF-BB collaboratively modulate perivascular cell coverage in tumor vessels, thus providing mechanistic insights of pericyte-endothelial cell interactions in TME and conceptual implications for treatment of cancers and other diseases by targeting the FGF-2-FGFR-pericyte axis

Biochar increased soil respiration in temperate forests but had no effects in subtropical forests

© 2017 Elsevier B.V. As a climate change mitigation strategy, biochar application to soil has been demonstrated to increase soil carbon (C) sequestration and reduce greenhouse gas (GHG) emission. Although numerous manipulative studies have been conducted, it is still not fully understood how biochar application affects soil respiration (Rs) and its components (i.e., autotrophic [Ra] and heterotrophic respiration [Rh] ) in forest ecosystems, especially in subtropical forests. In this study, we performed a meta-analysis of forest ecosystems and a field experiment with biochar amendments of 0, 10, and 30 t ha −1 in a subtropical forest in Zhejiang, China to examine the effects of biochar application on Rs and its components. Our results showed that biochar application significantly increased Rs by 20.92% at the global scale with an increase of 20.25% in temperate forests and a nonsignificant effect in subtropical forests. Responses of Rs to biochar application varied with experimental methods and soil textures. Similarly, our field experiment showed that biochar amendment did not significantly affect Ra, Rh, and Rs in a subtropical forest in Eastern China. Specifically, the average Rs under biochar amendments of 0, 10, and 30 t ha −1 were 2.37, 2.06 and 2.15 μmol m −2 s −1 , respectively (P > 0.05). Both Rs and Rh were positively correlated with microbial biomass C (MBC) and negatively with dissolved organic C (DOC). Both apparent temperature sensitivity (Q 10 ) of Rh and Rs were significantly higher under biochar treatments than in the control. Our findings indicate the importance of the differential effects of biochar application on Rs in different forest types for C sequestration, which may inform ecosystem and regional models to improve prediction of biochar effects on forest C dynamics and climate-biosphere feedbacks

Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy.

Long-term uninterrupted therapy is essential for maximizing clinical benefits of antiangiogenic drugs (AADs) in cancer patients. Unfortunately, nearly all clinically available AADs are delivered to cancer patients using disrupted regimens. We aim to develop lifetime, nontoxic, effective, orally active, and low-cost antiangiogenic and antitumor drugs for treatment of cancer patients. Here we report our findings of long-term maintenance therapy with orally active, nontoxic, low cost antiangiogenic chemotherapeutics for effective cancer treatment. In a sequential treatment regimen, robust antiangiogenic effects in tumors were achieved with an anti-VEGF drug, followed by a low-dose chemotherapy. The nontoxic, low dose of the orally active prodrug capecitabine was able to sustain the anti-VEGF-induced vessel regression for long periods. In another experimental setting, maintenance of low-dose capecitabine produced greater antiangiogenic and antitumor effects after AAD plus chemotherapy. No obvious adverse effects were developed after more than 2-mo of consecutive treatment with a low dose of capecitabine. Together, our findings provide a rationalized concept of effective cancer therapy by long-term maintenance of AAD-triggered antiangiogenic effects with orally active, nontoxic, low-cost, clinically available chemotherapeutics

Off-tumor targets compromise antiangiogenic drug sensitivity by inducing kidney erythropoietin production.

Anti-VEGF drugs are commonly used for treatment of a variety of cancers in human patients, and they often develop resistance. The mechanisms underlying anti-VEGF resistance in human cancer patients are largely unknown. Here, we show that in mouse tumor models and in human cancer patients, the anti-VEGF drug-induced kidney hypoxia augments circulating levels of erythropoietin (EPO). Gain-of-function studies show that EPO protects tumor vessels from anti-VEGF treatment and compromises its antitumor effects. Loss of function by blocking EPO function using a pharmacological approach markedly increases antitumor activity of anti-VEGF drugs through inhibition of tumor angiogenesis. Similarly, genetic loss-of-function data shows that deletion of EpoR in nonerythroid cells significantly increases antiangiogenic and antitumor effects of anti-VEGF therapy. Finally, in a relatively large cohort study, we show that treatment of human colorectal cancer patients with bevacizumab augments circulating EPO levels. These findings uncover a mechanism of desensitizing antiangiogenic and anticancer effects by kidney-produced EPO. Our work presents conceptual advances of our understanding of mechanisms underlying antiangiogenic drug resistance

Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK.

Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti-VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases. Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti–VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990–2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408–868 574) to 2·17 million (2·00–2·34), and deaths increased from 518 126 (493 682–537 877) to 1·09 million (1·02–1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3–23·0) per 100 000 to 26·7 (24·6–28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5–14·9) per 100 000 to 13·7 (12·6–14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7–320·7) per 100 000 to 295·5 (275·2–313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9–80·0] per 100 000), Monaco (60·7 [48·5–73·6] per 100 000), and Andorra (56·6 [42·8–71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0–37·1] per 100 000), Brunei (30·3 [26·6–34·1] per 100 000), and Hungary (28·6 [23·6–34·0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age Interpretation The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possible reconsideration of screening guidelines. The fast-rising burden in low SDI and middle SDI countries in Asia and Africa calls for colorectal cancer prevention approaches, greater awareness, and cost-effective screening and therapeutic options in these regions.</p