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New Findings: What is the central question of this study?What is the mechanism of miR‐211 in an Alzheimer's disease cell model?What is the main finding and its importance?miR‐211 was upregulated in an Alzheimer's disease cell model. It targeted neurogenin 2, reduced the activation of the phosphoinositide 3‐kinase–Akt signalling pathway, inhibited the proliferation of the Alzheimer's disease cell model and promoted apoptosis. MicroRNAs (miRs) are aberrantly expressed in Alzheimer's disease (AD) patients. This study was intended to investigate the effect of miR‐211 on an AD cell model and the involvement of neurogenin 2 (Ngn2). The appropriate dose and time for the effect of Aβ1–42 on PC12 cells were determined to establish an AD cell model. An effect of miR‐211 expression on cell viability, proliferation and apoptosis was detected after cell transfection. Online prediction and a dual luciferase reporter gene assay were utilized to confirm the binding sequence of miR‐211 and Ngn2. qRT‐PCR and western blot analysis were applied to measure Ngn2 expression. A gain and loss of function assay of miR‐211 and Ngn2 was performed, and activation of the phosphoinositide 3‐kinase (PI3K)–Akt signaling pathway was detected. The AD cell model was induced by Aβ1–42 treatment. miR‐211 expression was significantly enhanced after miR‐211 transfection, leading to suppressed proliferation and promotion of apoptosis in Aβ1–42‐treated PC12 cells. In addition, miR‐211 could downregulate Ngn2 mRNA and protein expression, while overexpression of Ngn2 could reverse the effects of miR‐211 on Aβ1–42‐treated PC12 cells and significantly enhance the phosphorylated Akt and PI3K protein levels. miR‐211 could inhibit growth of PC12 cells by suppressing Ngn2 expression and inactivating the PI3K–Akt signalling pathway. [ABSTRACT FROM AUTHOR]

It is usually assumed that different lines of business are independent, but the fact is that they are dependent to some extent in multi-lines of business. Their dependence may be captured by Vine Copula functions. Vine Copula is a powerful tool to solve multiple dependence. Under the assumption that the incremental paid claims of every line of business follows gamma distribution, inverse-Gaussian distribution and log-normal distribution, respectively, the corresponding Vine Copula regression models are established. The model is applied to a real data set of auto insurance and the result shows that the Vine Copula-based regression model is superior to independent regression models in claims reserving. [ABSTRACT FROM AUTHOR]

SUMMARY: Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non‐model tree species are not yet fully understood. To address this issue, we generated whole‐genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long‐term refugial isolation and recent differential introgression in low‐recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values. Significance Statement: We assembled a chromosome‐scale genome of Liquidambar formosana and resequenced 160 individuals of L. formosana and its high‐altitude sister species L. acalycina. Benefiting from advanced analytical methods and robust evidence, we found that multiple "genomic islands" mainly evolved as a result of divergence hitchhiking and recombination rate variation, as likely fostered by long‐term refugial isolation and recent differential introgression in low‐recombination genomic regions; and identified some candidate genes associated with climatic adaptation and reproductive isolation. [ABSTRACT FROM AUTHOR]

Determination of major cations in soil extracts is important for soil research. This study introduced a new buffer system (Buf-I) for capillary-zone electrophoresis (CZE) for the detection of major cations in soil. The Buf-I system achieved baseline separation of major cations with a wider detection range, in less time, and with better reproducibility than the old buffer system (Buf-M). Storage stability and running stability experiments showed that the running current of Buf-I was also more stable and the relative standard deviation (RSD%) was significantly less than those of Buf-M. The recovery (91.13–107.64%) by Buf-I was better than that (78.38–103.87%) by Buf-M. The results by Buf-I method were highly consistent with traditional analysis techniques (with a correlation of 0.9963). Therefore, we conclude that the new Buf-I system is more stable and accurate than the old Buf-M system and is especially suitable to determine major cations in soil extract. [ABSTRACT FROM AUTHOR]

Objective. We demonstrated that circulating microparticles (MPs) are increased in patients with coronary heart disease (both chronic coronary syndrome (CCS) and acute coronary syndrome). Whether thrombolysis affects MPs in patients with ST-segment elevation myocardial infarction (STEMI) with or without percutaneous coronary intervention (PCI) is unknown. Methods. This study was divided into three groups: STEMI patients with thrombolysis (n = 18) were group T, patients with chronic coronary syndrome (n = 20) were group CCS, and healthy volunteers (n = 20) were the control group. Fasting venous blood was extracted from patients in the CCS and control groups, and venous blood was extracted from patients in the T group before (pre-T) and 2 hours after (post-T) thrombolysis. MPs from each group were obtained by centrifugation. After determining the concentration, the effects of MPs on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rat myocardial tissue in vitro were detected by immunohistochemistry and western blotting. Changes in nitric oxide (NO) and oxygen free radicals (O2•–) were also detected. The effect of MPs on vasodilation in isolated rat thoracic aortae was detected. Results. Compared with that in the control group (2.60 ± 0.38 mg/ml), the concentration of MPs was increased in patients with CCS (3.49 ± 0.72 mg/ml) and in STEMI patients before thrombolysis (4.17 ± 0.58 mg/ml). However, thrombolysis did not further increase MP levels (post-T, 4.23 ± 1.01 mg/ml) compared with those in STEMI patients before thrombolysis. Compared with those in the control group, MPs in both CCS and STEMI patients before thrombolysis inhibited the expression of eNOS (both immunohistochemistry and western blot analysis of phosphorylation at Ser1177), NO production in the isolated myocardium and vasodilation in vitro and stimulated the expression of iNOS (immunohistochemistry and western blot analysis of phosphorylation at Thr495), and the generation of O2•– in the isolated myocardium. The effects of MPs were further enhanced by MPs from STEMI patients 2 hours after thrombolysis. Conclusion. Changes in MP function after thrombolysis may be one of the mechanisms leading to ischemia–reperfusion after thrombolysis. [ABSTRACT FROM AUTHOR]

Objective. High-density lipoprotein (HDL) was found vasoprotective, but numbers of patients with acute myocardial infarction (AMI) have normal or even high levels of pathological HDL (pHDL). So, we investigate the mechanism of pHDL in AMI patients on angiogenesis. Methods. HDL with normal levels from healthy subjects (nHDL, control group, n = 20) and patients with AMI (pHDL, experimental groups, n = 30) were obtained by super high speed centrifugation. Then, effects of HDL on proliferation, migration, angiogenesis, and expression of ERK1/2 and its phosphorylation in human umbilical vein endothelial cells (HUVEC) with or without PD98059 (inhibitor of ERK1/2) preincubation were detected. Results. Compared with the control group (nHDL), HDL from the experimental group (pHDL) significantly inhibited the phosphorylation of ERK1/2, proliferation, migration, and angiogenesis of HUVEC (P < 0.05), while these effects of HDL could substantially be blocked by preincubation of PD98059 (P < 0.05). Conclusion. HDL in AMI patients affects angiogenesis by inhibiting ERK1/2 activation free from HDL levels. [ABSTRACT FROM AUTHOR]

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties. However, it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage (SAH). This study explores the effect of paeoniflorin on early brain injury (EBI) using rat SAH model. We found that paeoniflorin significantly improves neurological deficits, attenuates brain water content and Evans blue extravasation at 72 h after SAH. Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species (ROS), malondialdehyde (MDA), 3-Nitrotyrosine, and 8-Hydroxy-2-deoxy guanosine (8-OHDG) level, increase of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activity, and up-regulates the nuclear factor erythroid‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO-1) pathway. Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin's protective effects. Moreover, paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2, active caspase-3/ neuronal nuclei (NeuN) and TUNEL/DAPI positive cells at 72 h following SAH. Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH. [ABSTRACT FROM AUTHOR]

Introduction Platelet activation participates in the development of both coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly used medicine for coronary heart disease, whether aspirin affects the function of MPs remains unclear. Aims This study was designed to test MPs from healthy subjects, and stable angina (SA) patients before and after aspirin administration were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs (with or without aspirin) to determine the effects of MPs on expression of ERK1/2, JNKs, and p38 MAPK. Affect on levels of NF-κB, VCAM-1, NO, and O2-. Results Compared with healthy subjects, MPs concentrations increased in SA patients, but decreased after aspirin administration. According to flow cytometry, aspirin mainly decreased platelet-derived MP. MPs from SA patients decreased the expression of ERK1/2, increased expression of p38 MAPKs, JNKs. Increased NF-κB, VCAM-1, and (O2-) levels decreased NO content. Aspirin therapy significantly inhibited function of MPs from SA patients, and pathway inhibitors (ERK1/2 inhibitor PD98059, p38 MAPKs inhibitor SB203580, NF-kB inhibitor PDTC) show similar effects with aspirin. Conclusion These results indicate that the pro-inflammatory, oxidative stress, procoagulant, and adhesion properties of MPs can be partly blocked by aspirin via the ERK-NO/O2- and p38 -NF-κB-VCAM-1 signal pathway, which clarified other functions beyond anti-atherothrombotic of aspirin. [ABSTRACT FROM AUTHOR]

Abstract: This review was to assess the concentration changing trends of various cytokines in plasma of epilepsy patients after recent seizure, as well as to assess the differences between temporal lobe epilepsy (TLE) and extra-TLE (XLE) patients. We performed a meta-analysis of studies measuring cytokine concentration in plasma of patients suffering from epilepsy after recent seizure, by searches of the English literature in Pubmed and Embase databases (to July 1st 2010) and a manual search of references. A random-effects model was used to do accumulative analysis for the included studies by RevMan 5.0 software. Eight studies were included and analyzed. We found the plasma concentrations of interleukin-6 (IL-6) within 72h after seizure were significantly increased in epileptic patients compared with control subjects (211 epilepsy patients vs. 564 controls, overall weighted mean difference 1.27pg/ml, 95% confidence interval 0.72–1.82, P <0.0001). There were no significant differences for IL-1 beta and, IL-1 receptor antagonist (IL-1RA) between the two groups. The concentration changes of IL-6 and IL-1RA were not significantly different between TLE patients and XLE patients. The result of this meta-analysis revealed significantly higher concentrations of the pro-inflammatory cytokines IL-6 in epileptic seizure patients compared with control subjects. Further rigorous studies are needed to clarify the precise role of cytokines in epilepsy. [Copyright &y& Elsevier]

As a common factor of both type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS), circulating microparticles (MPs) may provide a link between these two diseases. The present study compared the content and function of MPs from patients with ACS with or without T2DM. MPs from healthy subjects (n=20), patients with ACS (n=24), patients with T2DM (n=20) and patients with combined ACS and T2DM (n=24) were obtained. After incubating rat thoracic tissue with MPs, the effect of MPs on endothelial-dependent vasodilatation, expression of caveolin-1 and endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS at the S1177 and T495 sites and its association with heat shock protein 90 (Hsp90), and the generation of NO and superoxide anion (O2˙-) were determined. MP concentrations were higher in patients with T2DM and patients with ACS with or without T2DM than in healthy subjects. Moreover, MPs from patients with T2DM or ACS led to impairment in endothelial-dependent vasodilatation, decreased expression of NO, as well as eNOS and its phosphorylation at Ser1177 and association with Hsp90, but increased eNOS phosphorylation at T495, caveolin-1 expression and O2˙- generation. These effects were strengthened by MPs from patients with ACS combined with T2DM. T2DM not only increased MP content but also resulted in greater vascular impairment effects in ACS. These results may provide novel insight into the treatment of patients with ACS and T2DM. [ABSTRACT FROM AUTHOR]