Silver-Catalyzed Long-Distance Aryl Migration from Carbon Center to Nitrogen Center

Selective cleavage of an inert C–C bond followed by C–O/N bond formation through a long-distance aryl migration from a carbon to a nitrogen center via Ag catalysis is reported. The migration products were easily converted into γ-hydroxy amines and tetrahydro­quinoline derivatives in quantitative yields. Preliminary mechanistic studies indicated a radical pathway

Redox-Divergent Hydrogen-Retentive or Hydrogen-Releasing Synthesis of 3,4-Dihydroisoquinolines or Isoquinolines

A rare Ru-catalyzed highly selective synthesis of 3,4-dihydroisoquinolines or isoquinolines is accomplished via a redox-divergent hydrogen-retentive or hydrogen-releasing fashion. Notably, high <i>cis</i>-selectivity of 3,4-dihydroisoquinolines is achieved. Potential applications are shown by gram-scale reactions and very concise synthesis of N-containing polycyclic aromatic compounds. Primary mechanistic investigations indicate that the sequence of the major pathway involves Ru-catalyzed C–H activation, alkyne insertion, and subsequent 6π-electrocyclization

Redox-Divergent Hydrogen-Retentive or Hydrogen-Releasing Synthesis of 3,4-Dihydroisoquinolines or Isoquinolines

A rare Ru-catalyzed highly selective synthesis of 3,4-dihydroisoquinolines or isoquinolines is accomplished via a redox-divergent hydrogen-retentive or hydrogen-releasing fashion. Notably, high <i>cis</i>-selectivity of 3,4-dihydroisoquinolines is achieved. Potential applications are shown by gram-scale reactions and very concise synthesis of N-containing polycyclic aromatic compounds. Primary mechanistic investigations indicate that the sequence of the major pathway involves Ru-catalyzed C–H activation, alkyne insertion, and subsequent 6π-electrocyclization

mRNA expression of senescence-associated genes in K562 cells treated with 50 nM DOX as measured by real-time quantitative RT-PCR.

<p>The x-axis indicates the days post DOX treatment and the y-axis represents the relative mRNA expression level. The value of the mRNA expression at day 0 is designated 1, and the levels of all other days are calibrated to this value. Data represented are the means and SE of 5 independent experiments.</p

Expression of putative <i>miR-375</i> target genes in DOX-induced senescent K562 cells.

<p>(A) mRNA expression of putative <i>miR-375</i> target genes in K562 cells treated with 50 nM DOX for 3 and 4 days as measured by real-time quantitative RT-PCR. The value of the mRNA expression in untreated K562 cells of the same day is designated 1, and the level of mRNA expression of DOX-treated K562 cells are calibrated to this value. Data represented are the means and SE of 5 independent experiments. (B) Expression of <i>14-3-3zeta</i>, <i>LDHB</i>, and <i>SP1</i> genes in K562 cells treated with 50 nM DOX (<i>DOX</i>) transfected with 100 nM <i>has-</i>anti-<i>miR-375</i> inhibitor followed by 50 nM DOX treatment (<i>Inh</i>) or transfected with 100 nM <i>has</i>-<i>miR-375</i> precursor (<i>Pre</i>) for 3 and 4 days. The calculation of gene expression was as described in (A). Data represented are the means and SE of 3 independent experiments.</p

DOX induced senescence but PTX not senescence in K562 cells.

<p>(A) K562 cells treated with 50 nM of DOX for 4 days were stained for SA-β-gal activity followed by DAPI staining. Original magnification is 400×. Representative microscopic fields are shown. (B) K562 cells were treated with 50 nM of DOX for 5 days, and the percentages of apoptotic cells were determined by Annexin V/PI staining followed by flow cytometric analysis. Data represented are the means and SE of 3 independent experiments. (C) K562 cells were treated with 50 nM of DOX for 5 days, and DNA contents were measured by flow cytometric analysis after PI staining. Data represented are the means and SE of 3 independent experiments.</p

<i>miR-375</i> is upregulated in DOX-induced senescent K562 cells.

<p>(A) miRNAs upregulated in 50 nM DOX-treated K562 cells for 4 days as measured by TaqMan® microRNA microarray analysis. The value of the miRNA expression in untreated K562 cells of day 4 is designated 1, and the level of miRNA expression of DOX-treated K562 cells are calibrated to this value. Data represented are the means and SE of 3 independent experiments. (B) Validation of miRNA expression by individual mature TaqMan® microRNA assays using real-time quantitative RT-PCR. The 4 most strongly expressed miRNAs selected from TaqMan® microRNA microarray analysis were further validated. The value of the miRNA expression in untreated K562 cells is designated 1, and the level of miRNA expression of DOX-treated K562 cells of the same day are calibrated to this value. Data represented are the means and SE of 3 independent experiments. (C) Inhibition of <i>has</i>-<i>miR-375</i> by 100 nM <i>has</i>-anti-<i>miR-375</i> inhibitor or 100 nM <i>has</i>-anti-<i>miR-375</i> inhibitor scramble negative control (SC) in K562 cells. After transfection for 48 hours, K562 cells were treated with 50 nM DOX for 5 days. The expression of mature <i>has</i>-<i>miR-375</i> was examined by TaqMan® microRNA assays using real-time quantitative RT-PCR. The value of the <i>has</i>-<i>miR-375</i> expression at day 0 is designated 1, and the levels of all other days of the same treatment are calibrated to this value. Data represented are the means and SE of 5 independent experiments. (D) WST-1 assay was performed to determine cell proliferation after 100 nM <i>has-</i>anti-<i>miR-375</i> inhibitor or 100 nM <i>has</i>-anti-<i>miR-375</i> inhibitor SC transfection followed by 50 nM DOX treatment in K562 cells. Data represented are the means and SE of 5 independent experiments. *Indicates significant difference compared to cells treated with 50 nM DOX and treated with 100 nM anti<i>-miR-375</i> SC and 50 nM DOX (<i>p</i><0.05). (E) Overexpression of <i>miR-375</i> by 100 nM <i>has</i>-<i>miR-375</i> precursor or 100 nM <i>has</i>-<i>miR-375</i> precursor SC in K562 cells. The measurement and calculation of mature <i>has</i>-<i>miR-375</i> expression were as described in (C). Data represented are the means and SE of 5 independent experiments. (F) WST-1 assay was performed to determine cell proliferation after 100 nM <i>has</i>-<i>miR-375</i> precursor or 100 nM <i>has</i>-<i>miR-375</i> precursor SC transfection in K562 cells. Data represented are the means and SE of 5 independent experiments. *Indicates significant difference compared to both untreated K562 cells and cells treated with 100 nM <i>has</i>-<i>miR-375</i> precursor SC (<i>p</i><0.05).</p

Nonapnea Sleep Disorders in Patients Younger than 65 Years Are Significantly Associated with CKD: A Nationwide Population-Based Study

<div><p>Background</p><p>Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.</p><p>Methods</p><p>We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.</p><p>Results</p><p>The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26–1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23–1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19–1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35–2.40, p< 0.001).</p><p>Conclusions</p><p>In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.</p></div

Cox proportional hazards regression model for risk of CKD between the NSAD cohort and control cohort (N = 28,024).

<p>Adjusted age, gender, index year, urbanization, regions, monthly Income, visit ambulatory frequency, and comorbidities (hypertension, diabetes, hyperlipidemia, cardiovascular disease, cerebral vascular disease, liver disease, gout, obesity, depression).</p><p>Cox proportional hazards regression model for risk of CKD between the NSAD cohort and control cohort (N = 28,024).</p

Cumulative incidence of CKD in the NASD (dash line) and control (solid) cohorts.

<p>Cumulative incidence of CKD in the NASD (dash line) and control (solid) cohorts.</p