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Patients with chronic kidney disease have an increased prevalence of peripheral arterial disease. Endothelial progenitor cells (EPC) are pivotal in neovascularization, but their role in mediating peripheral arterial disease in chronic kidney disease is not fully known. Here we studied the impact of indoxyl sulfate, a protein-bound uremic toxin, on EPC function in response to tissue ischemia or cell hypoxia in mice that underwent subtotal nephrectomy or sham operation. At 16 weeks, unilateral hindlimb ischemia was induced in all. Four weeks later, subtotal nephrectomy mice had significantly increased plasma levels of indoxyl sulfate, reduced reperfusion, decreased EPC mobilization, and impaired neovascularization in ischemic hindlimbs compared with control mice. Treatment with AST-120, an oral adsorbent of uremic toxins, reversed these changes. Ischemia-induced protein expression including phospho-eNOS, phospho-STAT3, interleukin-10, and VEGF were significantly decreased in ischemic hindlimbs of subtotal nephrectomy mice versus control mice; all effects were reversed by AST-120. Subtotal nephrectomy mice fed a diet with indole for 12 weeks resulted in impaired neovascularization in ischemic hindlimbs; also reversed by AST-120. In cultured human EPCs, VEGF expression was increased in hypoxia through HIF-1α and interleukin-10/STAT3 signaling; effects suppressed by pretreatment with indoxyl sulfate. Moreover, indoxyl sulfate markedly attenuated hypoxia-induced EPC migration and tube formation. Thus, indoxyl sulfate may be a therapeutic target for EPC-rescue of impaired neovascularization in patients with chronic kidney disease and peripheral arterial disease.

A stacked oxide semiconductor of n-type ZnO/p-type NiO with diode behavior was proposed as the novel charge-trapping layer to enable low-voltage flash memory for green electronics. The memory performance outperforms that of other devices with high κ and a nanocrystal-based charge-trapping layer in terms of a large hysteresis memory window of 2.02 V with ±3 V program/erase voltage, a high operation speed of 1.88 V threshold voltage shift by erasing at −4 V for 1 ms, negligible memory window degradation up to 105operation cycles, and 16.2% charge loss after 10 years of operation at 85 °C. The promising electrical characteristics can be explained by the negative conduction band offset with respect to Si of ZnO that is beneficial to electron injection and storage, the large number of trapping sites of NiO that act as other good storage media, and most importantly the built-in electric field between n-type ZnO and p-type NiO that provides a favorable electric field for program and erase operation. The process of diode-based flash memory is fully compatible with incumbent VLSI technology, and utilization of the built-in electric field ushers in a new avenue of accomplishing green flash memory.

Electron transport is critical to the use of n-type semiconducting polymers in diverse electronic and optoelectronic devices. Herein, we combine measurements of field-effect electron mobility and bulk electron mobility with thin-film microstructure characterization to elucidate the polymer chain length dependence of electron transport in n-type semiconducting polymers, exemplified by a naphthalene diimide-biselenophene copolymer, PNDIBS. Both bulk electron mobility measured by the space–charge limited current method and field-effect electron mobility of PNDIBS and other n-type semiconducting copolymers exhibit a peak at a critical degree of polymerization (DPc) of 45–60 repeat units. The decreased electron mobility below DPcis shown to originate from reduced intercrystallite connectivity while above DPc, intrachain twisting/folding, interchain entanglements, and intracrystallite limitations dominate electron transport. These findings provide a unified picture of the effects of polymer molecular weight on electron transport in naphthalene diimide-based polymers and offer a more quantitative design rule for high-mobility n-type polymers with donor–acceptor architecture.

The safety of herbal products is one of the major concerns for the modernization of traditional Chinese medicine, and pharmacokinetic data of medicinal herbs guide us to design the rational use of the herbal formula. This article reviews the advantages of the automated blood sampling (ABS) systems for pharmacokinetic studies. In addition, three commonly used sample preparative methods, protein precipitation, liquid-liquid extraction and solid-phase extraction, are introduced. Furthermore, the definition, causes and evaluation of matrix effects in liquid chromatography-mass spectrometry (LC/MS) analysis are demonstrated. Finally, we present our previous works as practical examples of the application of ABS systems and LC/MS for the pharmacokinetic studies of Chinese medicinal herbs.

ABSTRACTA novel pandemic influenza H1N1 (pH1N1) virus spread rapidly across the world in 2009. Due to the important role of antibody-mediated immunity in protection against influenza infection, we used an enzyme-linked immunosorbent assay-based microneutralization test to investigate cross-reactive neutralizing antibodies against the 2009 pH1N1 virus in 229 stored sera from donors born between 1917 and 2008 in Taiwan. The peak of cumulative geometric mean titers occurred in donors more than 90 years old and declined sharply with decreasing age. Sixteen of 27 subjects (59%) more than 80 years old had cross-reactive antibody titers of 160 or more against the 2009 pH1N1 virus, whereas none of the donors from age 9 to 49 had an antibody titer of 160 or more. Interestingly, 2 of 51 children (4%) from 6 months to 9 years old had an antibody titer of 40. We further tested the antibody responses in 9 of the 51 pediatric sera to three endemic seasonal influenza viruses isolated in 2006 and 2008 in Taiwan, and the results showed that only the 2 sera from children with antibody responses to the 2009 pH1N1 virus had high titers of neutralizing antibody against recent seasonal influenza virus strains. Our study shows the presence of some level of cross-reactive antibody in Taiwanese persons 50 years old or older, and the elderly subjects who may already have been exposed to the 1918 virus had high titers of neutralizing antibody to the 2009 pH1N1 virus. Our data also indicate that natural infection with the Taiwan 2006 and 2008 seasonal H1N1 viruses may induce a cross-reactive antibody response to the 2009 pH1N1 virus.

To characterize the pathway of ceftriaxone penetration into intervertebral discs, rat-tail discs were collected and immersed in a ceftriaxone solution for an in vitrostudy. For this in vivoexperiment, plasma and tail discs were collected 30 min after ceftriaxone administration (463.2 mg/kg, equal to 500 mg/kg disodium salt, iv). The ceftriaxone levels in the plasma and discs were determined with HPLC by a reversed-phase C18 column and a mobile phase of methanol and a 10 mM K2HPO4solution (pH 6.7) (21:79, v/v). The results indicate that ceftriaxone was undetectable by the in vitromodel. The concentrations of ceftriaxone in plasma and in intervertebral discs were 147.4 ± 21.2 and 4.0 ± 1.7 μg/mL (as disodium salt), respectively. Our results suggest that a sufficient blood supply is required for the passive diffusion of ceftriaxone into intervertebral discs. The concentration ratio of ceftriaxone in intervertebral disc-to-plasma was about 2.7% at 30 min after ceftriaxone disodium administration (500 mg/kg, iv).

This study was designed to determine the clinical characteristics of children infected with different strains of influenza B viruses isolated in southern Taiwan. The clinical features were compared with influenza A infection occurring in the same period.

ABSTRACTStaphylococcus aureusis an important cause of community-associated bacteremia (SAB) and infective endocarditis (IE). No significant differences in distribution or frequency of genes encoding virulence factors, including genes encoding adhesins, were found between isolates from the IE and SAB groups (12 IE and 10 SAB patients).

With Si substrate, Ge-based nonvolatile memory devices with the charge trapping layer and tunnel dielectric respectively formed by a Ge-stabilized tetragonal ZrO2film and a thermal GeO2film are explored in this work. A 1.8-V memory window is achieved by program/erase (P/E) at ±5 V for 1 ms which proves high-speed/low-voltage operation and this desirable characteristic is mainly due to the crystalline ZrO2trapping layer which provides a high permittivity of 36.8 with a large amount of trapping sites. A negligible degradation of memory window up to 105P/E cycles can be accomplished by applying gate pulse of ±5 V for 1 ms and it demonstrates that the thermal GeO2film is robust enough to offer the required reliability. Good retention characteristics with 70% charge after a 10 year operation at 85°C also affirm the eligibility of GeO2as the tunnel dielectric. These results suggest that this novel device structure holds great potential for future high-performance memory.