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Abstract Background Long intergenic non-coding RNA 00511 (LINC00511) is highly expressed in diverse cancers and has a correlation with poor clinical outcomes for cancer patients. In view of contradictory data among published data, we aim to evaluate the prognostic role of LINC00511 for cancer patients. Methods In the present study, a meta-analysis of related studies has been performed to investigate the prognostic significance of LINC00511 in cancer patients. Relevant studies published before December 22, 2019 were systematically searched online in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. The relationship between LINC00511 expression and cancer patients’ survival, including overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS) and progression-free survival (PFS), was evaluated using pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). The association between LINC00511 expression and clinicopathological features was assessed using odd ratios (ORs) and their corresponding 95% CIs. Results A total of 14 eligible studies with 1883 patients were enrolled in the present meta-analysis. The results demonstrated that elevated expression of LINC00511 was significantly associated with poor OS (HR = 2.62; 95% CI: 2.00–3.45; p

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.

RationalePhosPhatidic Acid Phosphatase type 2B (PPAP2B), an integral membrane protein known as lipid phosphate phosphatase (LPP3) that inactivates lysophosphatidic acid, was implicated in coronary artery disease (CAD) by genome-wide association studies. However, it is unclear whether genome-wide association studies-identified coronary artery disease genes, including PPAP2B, participate in mechanotransduction mechanisms by which vascular endothelia respond to local atherorelevant hemodynamics that contribute to the regional nature of atherosclerosis.ObjectiveTo establish the critical role of PPAP2B in endothelial responses to hemodynamics.Methods and resultsReduced PPAP2B was detected in vivo in mouse and swine aortic arch (AA) endothelia exposed to chronic disturbed flow, and in mouse carotid artery endothelia subjected to surgically induced acute disturbed flow. In humans, PPAP2B was reduced in the downstream part of carotid plaques where low shear stress prevails. In culture, reduced PPAP2B was measured in human aortic endothelial cells under atherosusceptible waveform mimicking flow in human carotid sinus. Flow-sensitive microRNA-92a and transcription factor KLF2 were identified as upstream inhibitor and activator of endothelial PPAP2B, respectively. PPAP2B suppression abrogated atheroprotection of unidirectional flow; inhibition of lysophosphatidic acid receptor 1 restored the flow-dependent, anti-inflammatory phenotype in PPAP2B-deficient cells. PPAP2B inhibition resulted in myosin light-chain phosphorylation and intercellular gaps, which were abolished by lysophosphatidic acid receptor 1/2 inhibition. Expression quantitative trait locus mapping demonstrated PPAP2B coronary artery disease risk allele is not linked to PPAP2B expression in various human tissues but significantly associated with reduced PPAP2B in human aortic endothelial cells.ConclusionsAtherorelevant flows dynamically modulate endothelial PPAP2B expression through miR-92a and KLF2. Mechanosensitive PPAP2B plays a critical role in promoting anti-inflammatory phenotype and maintaining vascular integrity of endothelial monolayer under atheroprotective flow.

C17H27N3OS2, monoclinic, P21 (no. 4), a = 8.8052(10) Å, b = 10.8860(10) Å, c = 18.6705(2) Å, β = 99.2730(10)°, V = 1766.24(3) Å3, Z = 4, Rgt(F) = 0.0298, wRref(F2) = 0.0802, T = 100.00(10) K.

Diosgenin, a natural steroidal sapogenin, has recently attracted a high amount of attention, as an effective anticancer agent in ovarian cancer. However, diosgenin mediated anticancer impacts are still not completely understood. Thus, the present study evaluated the effect of diosgenin on the proliferation, apoptosis, and metastasis of ovarian cancer cells. OVCAR‐3 and SKOV‐3 cells were treated with diosgenin, cellular viability was assessed by MTT assay and apoptosis was measured by ELISA and evaluated the protein expression levels of apoptotic markers through western blotting. Cell migration was examined by measuring the mRNA levels of genes involved in the cell invasion. The protein expression levels of main components of PI3K signaling were evaluated via western blotting. Diosgenin led to significant inhibition of cellular proliferation in a dose‐dependent manner. It also induced apoptosis through upregulating pro‐apoptotic markers and downregulating antiapoptotic mediators. In addition, OVCAR‐3 cells exposure to diosgenin decreased cell migration and invasion. More importantly, diosgenin downregulated the expression levels of main proteins in PI3K signaling including PI3K, Akt, mTOR, and GSK3. Diosgenin inhibited the proliferation and migration of OVCAR‐3 ovarian cancer cells and induced apoptosis, which may be mediated by targeting PI3K signaling. [ABSTRACT FROM AUTHOR]

Abstract Determining the factors promoting speciation is a major task in ecological and evolutionary research and can be aided by phylogeographic analysis. The Qinling–Daba Mountains (QDM) located in central China form an important geographic barrier between southern subtropical and northern temperate regions, and exhibit complex topography, climatic, and ecological diversity. Surprisingly, few phylogeographic analyses and studies of plant speciation in this region have been conducted. To address this issue, we investigated the genetic divergence and evolutionary histories of three closely related tree peony species (Paeonia qiui, P. jishanensis, and P. rockii) endemic to the QDM. Forty populations of the three tree peony species were genotyped using 22 nuclear simple sequence repeat markers (nSSRs) and three chloroplast DNA sequences to assess genetic structure and phylogenetic relationships, supplemented by morphological characterization and ecological niche modeling (ENM). Morphological and molecular genetic analyses showed the three species to be clearly differentiated from each other. In addition, coalescent analyses using DIYABC conducted on nSSR variation indicated that the species diverged from each other in the late Pleistocene, while ecological niche modeling (ENM) suggested they occupied a larger area during the Last Glacial Maximum (LGM) than at present. The combined genetic evidence from nuclear and chloroplast DNA and the results of ENM indicate that each species persisted through the late Pleistocene in multiple refugia in the Qinling, Daba, and Taihang Mountains with divergence favored by restricted gene flow caused by geographic isolation, ecological divergence, and limited pollen and seed dispersal. Our study contributes to a growing understanding of the origin and population structure of tree peonies and provides insights into the high level of plant endemism present in the Qinling–Daba Mountains of Central China.

Abstract Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 105 km2 is suitable for growing P. ostii, accounting for 21.16% of the country’s total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.

Abstract Background Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. Results Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. Conclusions Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.

BackgroundPrevious meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted.MethodsLiterature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed.ResultsTwelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60–0.76, p