One-pot synthesis of poly (3,4-ethylenedioxythiophene)-Pt nanoparticle composite and its application to electrochemical H2O2 sensor.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Poly(3,4-ethylenedioxythiophene)-Pt nanoparticle composite was synthesized in one-pot fashion using a photo-assisted chemical method, and its electrocatalytic properties toward hydrogen peroxide (H2O2) was investigated. Under UV irradiation, the rates of the oxidative polymerization of EDOT monomer along with the reduction of Pt4+ ions were accelerated. In addition, the morphology of PtNPs was also greatly influenced by the UV irradiation; the size of PtNPs was reduced under UV irradiation, which can be attributed to the faster nucleation rate. The immobilized PtNPs showed excellent electrocatalytic activities towards the electroreduction of hydrogen peroxide. The resultant amperometric sensor showed enhanced sensitivity for the detection of H2O2 as compared to that without PtNPs, i.e., only with a layer of PEDOT. Amperometric determination of H2O2 at -0.55 V gave a limit of detection of 1.6 μM (S / N = 3) and a sensitivity of 19.29 mA cm-2 M-1 up to 6 mM, with a response time (steady state, t95) of 30 to 40 s. Energy dispersive X-ray analysis, transmission electron microscopic image, cyclic voltammetry (CV), and scanning electron microscopic images were utilized to characterize the modified electrode. Sensing properties of the modified electrode were studied both by CV and amperometric analysis

RssAB Signaling Coordinates Early Development of Surface Multicellularity in Serratia marcescens

Bacteria can coordinate several multicellular behaviors in response to environmental changes. Among these, swarming and biofilm formation have attracted significant attention for their correlation with bacterial pathogenicity. However, little is known about when and where the signaling occurs to trigger either swarming or biofilm formation. We have previously identified an RssAB two-component system involved in the regulation of swarming motility and biofilm formation in Serratia marcescens. Here we monitored the RssAB signaling status within single cells by tracing the location of the translational fusion protein EGFP-RssB following development of swarming or biofilm formation. RssAB signaling is specifically activated before surface migration in swarming development and during the early stage of biofilm formation. The activation results in the release of RssB from its cognate inner membrane sensor kinase, RssA, to the cytoplasm where the downstream gene promoters are located. Such dynamic localization of RssB requires phosphorylation of this regulator. By revealing the temporal activation of RssAB signaling following development of surface multicellular behavior, our findings contribute to an improved understanding of how bacteria coordinate their lifestyle on a surface

Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia

Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen

Momentum matching and band-alignment type in van der Waals heterostructures: Interfacial effects and materials screening

Momentum-matched type II van der Waals heterostructures (vdWHs) have been designed by assembling layered two-dimensional semiconductors (2DSs) with special band-structure combinations - that is, the valence band edge at the Gamma point (the Brillouin-zone center) for one 2DS and the conduction band edge at the Gamma point for the other [Ubrig et al., Nat. Mater. 19, 299 (2020)]. However, the band offset sizes, band-alignment types, and whether momentum matched or not, all are affected by the interfacial effects between the component 2DSs, such as the quasichemical-bonding (QB) interaction between layers and the electrical dipole moment formed around the vdW interface. Here, based on density-functional theory calculations, first we probe the interfacial effects (including different QBs for valence and conduction bands, interface dipole, and, the synergistic effects of these two aspects) on band-edge evolution in energy and valley (location in the Brillouin zone) and the resulting changes in band alignment and momentum matching for a typical vdWH of monolayer InSe and bilayer WS2, in which the band edges of subsystems satisfy the special band-structure combination for a momentum-matched type II vdWH. Then, based on the conclusions of the studied interfacial effects, we propose a practical screening method for robust momentum-matched type II vdWHs. This practical screening method can also be applied to other band alignment types. Our current study opens a way for practical screening and designing of vdWHs with robust momentum-matching and band alignment type

An iron detection system determines bacterial swarming initiation and biofilm formation

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe3+) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. Addition of Fe3+, or loss of ICDH-Coumarin due to pvc deletion results in prolonged RssAB signaling activation, leading to delayed swarming initiation and increased biofilm formation. We further show that ICDH-Coumarin is able to chelate Fe3+ to switch off RssAB signaling, triggering swarming initiation and biofilm reduction. Our findings reveal a novel cellular system that senses iron levels to regulate bacterial surface lifestyle

Cardiovascular Outcomes in Acute Coronary Syndrome and Malnutrition: A Meta-Analysis of Nutritional Assessment Tools

Background: There is emerging evidence that malnutrition is associated with poor prognosis among patients with acute coronary syndrome (ACS). // Objectives: This study seeks to elucidate the prognostic impact of malnutrition in patients with ACS and provide a quantitative review of most commonly used nutritional assessment tools. // Methods: Medline and Embase were searched for studies reporting outcomes in patients with malnutrition and ACS. Nutritional screening tools of interest included the Prognostic Nutrition Index, Geriatric Nutritional Risk Index, and Controlling Nutritional Status. A comparative meta-analysis was used to estimate the risk of all-cause mortality and cardiovascular events based on the presence of malnutrition and stratified according to ACS type, ACS intervention, ethnicity, and income. // Results: Thirty studies comprising 37,303 patients with ACS were included, of whom 33.5% had malnutrition. In the population with malnutrition, the pooled mortality rate was 20.59% (95% CI: 14.95%-27.67%). Malnutrition was significantly associated with all-cause mortality risk after adjusting for confounders including age and left ventricular ejection fraction (adjusted HR: 2.66, 95% CI: 1.78-3.96, P = 0.004). There was excess mortality in the group with malnutrition regardless of ACS type (P = 0.132), ethnicity (P = 0.245), and income status (P = 0.058). Subgroup analysis demonstrated no statistically significant difference in mortality risk between individuals with and without malnutrition (P = 0.499) when using Controlling Nutritional Status (OR: 7.80, 95% CI: 2.17-28.07, P = 0.011), Geriatric Nutritional Risk Index (OR: 4.30, 95% CI: 2.78-6.66, P < 0.001), and Prognostic Nutrition Index (OR: 4.67, 95% CI: 2.38-9.17, P = 0.023). // Conclusions: Malnutrition was significantly associated with all-cause mortality risk following ACS, regardless of ACS type, ethnicity, and income status, underscoring the importance of screening and interventional strategies for patients with malnutrition

Robust and highly efficient hiPSC generation from patient non-mobilized peripheral blood-derived CD34+ cells using the auto-erasable Sendai virus vector

Background: Disease modeling with patient-derived induced pluripotent stem cells (iPSCs) is a powerful tool forelucidating the mechanisms underlying disease pathogenesis and developing safe and effective treatments. Patientperipheral blood (PB) cells are used for iPSC generation in many cases since they can be collected with minimuminvasiveness. To derive iPSCs that lack immunoreceptor gene rearrangements, hematopoietic stem and progenitorcells (HSPCs) are often targeted as the reprogramming source. However, the current protocols generally requireHSPC mobilization and/or ex vivo expansion owing to their sparsity at the steady state and low reprogrammingefficiencies, making the overall procedure costly, laborious, and time-consuming.Methods: We have established a highly efficient method for generating iPSCs from non-mobilized PB-derivedCD34+ HSPCs. The source PB mononuclear cells were obtained from 1 healthy donor and 15 patients and werekept frozen until the scheduled iPSC generation. CD34+ HSPC enrichment was done using immunomagnetic beads,with no ex vivo expansion culture. To reprogram the CD34+-rich cells to pluripotency, the Sendai virus vectorSeVdp-302L was used to transfer four transcription factors: KLF4, OCT4, SOX2, and c-MYC. In this iPSC generationseries, the reprogramming efficiencies, success rates of iPSC line establishment, and progression time wererecorded. After generating the iPSC frozen stocks, the cell recovery and their residual transgenes, karyotypes, T cellreceptor gene rearrangement, pluripotency markers, and differentiation capability were examined.Results：We succeeded in establishing 223 iPSC lines with high reprogramming efficiencies from 15 patients with 8 different disease types. Our method allowed the rapid appearance of primary colonies (~ 8 days), all of which were expandable under feeder-free conditions, enabling robust establishment steps with less workload. After thawing, the established iPSC lines were verified to be pluripotency marker-positive and of non-T cell origin. A majority of the iPSC lines were confirmed to be transgene-free, with normal karyotypes. Their trilineage differentiation capability was also verified in a defined in vitro assay.Conclusion：This robust and highly efficient method enables the rapid and cost-effective establishment of transgene-free iPSC lines from a small volume of PB, thus facilitating the biobanking of patient-derived iPSCs and their use for the modeling of various diseases

Green Emission from a Strain-Modulated InGaN Active Layer

Strain-induced quantum dots (QDs) like island formations are demonstrated to effectively suppress pits/dislocation generation in high indium content (26.8%) InGaN active layers. In addition to the strain redistribution in the QD-like islands, strain modulation on the InGaN active layers by using the GaN island capping is employed to form an increased surface potential barrier around the dislocation cores, which inhibits the carrier transport to the surrounding dislocations. Cathodoluminescence shows distinct double-peak emissions at 503 nm and 444 nm, corresponding to the In-rich QD-like emission and the normal quantum well emission, respectively. The QD-like emission becomes dominated in photoluminescence due to the carrier localization effect of In-rich InGaN QDs at relatively low "carrier injection current". Accordingly, green emission may be enhanced by the following origins: (1) reduction in pits/dislocations density, (2) carrier localization and strain reduction in QDs, (3) strain modulation by GaN island capping, (4) enhanced light extraction with faceted GaN islands on the surface.National Natural Science Foundation of China [60876008, 61076091]; Program for New Century Excellent Talents in Fujian Province Universit

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy

The Silkworm (Bombyx mori) microRNAs and Their Expressions in Multiple Developmental Stages

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in various physiological processes through post-transcriptional regulation of gene expressions and are involved in development, metabolism, and many other important molecular mechanisms and cellular processes. The Bombyx mori genome sequence provides opportunities for a thorough survey for miRNAs as well as comparative analyses with other sequenced insect species. METHODOLOGY/PRINCIPAL FINDINGS: We identified 114 non-redundant conserved miRNAs and 148 novel putative miRNAs from the B. mori genome with an elaborate computational protocol. We also sequenced 6,720 clones from 14 developmental stage-specific small RNA libraries in which we identified 35 unique miRNAs containing 21 conserved miRNAs (including 17 predicted miRNAs) and 14 novel miRNAs (including 11 predicted novel miRNAs). Among the 114 conserved miRNAs, we found six pairs of clusters evolutionarily conserved cross insect lineages. Our observations on length heterogeneity at 5' and/or 3' ends of nine miRNAs between cloned and predicted sequences, and three mature forms deriving from the same arm of putative pre-miRNAs suggest a mechanism by which miRNAs gain new functions. Analyzing development-related miRNAs expression at 14 developmental stages based on clone-sampling and stem-loop RT PCR, we discovered an unusual abundance of 33 sequences representing 12 different miRNAs and sharply fluctuated expression of miRNAs at larva-molting stage. The potential functions of several stage-biased miRNAs were also analyzed in combination with predicted target genes and silkworm's phenotypic traits; our results indicated that miRNAs may play key regulatory roles in specific developmental stages in the silkworm, such as ecdysis. CONCLUSIONS/SIGNIFICANCE: Taking a combined approach, we identified 118 conserved miRNAs and 151 novel miRNA candidates from the B. mori genome sequence. Our expression analyses by sampling miRNAs and real-time PCR over multiple developmental stages allowed us to pinpoint molting stages as hotspots of miRNA expression both in sorts and quantities. Based on the analysis of target genes, we hypothesized that miRNAs regulate development through a particular emphasis on complex stages rather than general regulatory mechanisms