Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects

Towards Spontaneous Style Modeling with Semi-supervised Pre-training for Conversational Text-to-Speech Synthesis

The spontaneous behavior that often occurs in conversations makes speech more human-like compared to reading-style. However, synthesizing spontaneous-style speech is challenging due to the lack of high-quality spontaneous datasets and the high cost of labeling spontaneous behavior. In this paper, we propose a semi-supervised pre-training method to increase the amount of spontaneous-style speech and spontaneous behavioral labels. In the process of semi-supervised learning, both text and speech information are considered for detecting spontaneous behaviors labels in speech. Moreover, a linguistic-aware encoder is used to model the relationship between each sentence in the conversation. Experimental results indicate that our proposed method achieves superior expressive speech synthesis performance with the ability to model spontaneous behavior in spontaneous-style speech and predict reasonable spontaneous behavior from text.Comment: Accepted by INTERSPEECH 202

The effect of paternal psoriasis on neonatal outcomes: a nationwide population-based study

BackgroundPsoriasis is a chronic autoimmune disease involving both environmental and genetic risk factors. Maternal psoriasis often results in poor pregnancies that influence both mothers and newborns. However, the influence of paternal psoriasis on the newborn remains unknown. The aim of this study was to investigate whether paternal psoriasis is associated with increased risk of adverse neonatal outcomes, within a nationwide population-based data setting.MethodsSingleton pregnancies were identified in the Taiwan National Health Insurance database and National Birth Registry between 2004-2011 and classified into four study groups according to whether mothers and spouses had psoriasis (paternal(−)/maternal(−), paternal(+)/maternal(−), paternal(−)/maternal(+), and paternal(+)/maternal(+)). Data were analyzed retrospectively. Adjusted odds ratios (aOR) or hazard ratios (aHR) were calculated to evaluate the risk of neonatal outcomes between groups.ResultsA total of 1,498,892 singleton pregnancies were recruited. Newborns of fathers with psoriasis but not of mothers with psoriasis were associated with an aHR (95% CI) of 3.69 (1.65–8.26) for psoriasis, 1.13 (1.06–1.21) for atopic dermatitis and 1.05 (1.01–1.10) for allergic rhinitis. Newborns of mothers with psoriasis but not of fathers with psoriasis were associated with an aOR (95% CI) of 1.26 (1.12-1.43) for low birth weight (<2500 g) and 1.64 (1.10–2.43) for low Apgar scores, and an aHR of 5.70 (2.71–11.99) for psoriasis.ConclusionNewborns of fathers with psoriasis are associated with significantly higher risk of developing atopic dermatitis, allergic rhinitis and psoriasis. Caution is advised for adverse neonatal outcomes when either or both parents have psoriasis

Superfluid current through a dissipative quantum point contact

We measure superfluid transport of strongly-interacting fermionic lithium atoms through a quantum point contact with local, spin-dependent particle loss. We observe that the characteristic non-Ohmic superfluid transport enabled by high-order multiple Andreev reflections survives even at dissipation strength greater than the superfluid gap. We develop a model with mean-field reservoirs connected via tunneling to a dissipative site. Our calculations in the Keldysh formalism reproduce the observed non-equilibrium particle current, yet do not fully explain the observed loss rate or spin current

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective beta-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective beta1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were measured. Measurements were carried out at baseline and 0, 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in heart rate variability and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the β2-adrenoreceptor

Retroperitoneoscopic laparo-endoscopic single-site radical nephrectomy (RLESS-RN): initial experience with a homemade port

We successfully performed 6 LESS radical nephrectomy via the retroperitoneal approach (RLESS) using the Alexis wound retractor as a single access with conventional laparoscopic instruments. The results demonstrated that our RLESS technique of radical nephrectomy is a safe and feasible procedure for management of localized renal cancer

Stabilization of hybrid perovskite CH_3NH_3PbI_3 thin films by graphene passivation

We report the long-term stability of water-sensitive hybrid perovskites CH_3NH_3PbI_3 that were protected with monolayer graphene. This successful passivation was enabled by our development of a new water-free and polymer-free graphene transfer method. Monolayer graphene samples grown by plasma-enhanced chemical vapor deposition and transferred onto different substrates with the water/polymer-free method were found to preserve their high-quality characteristics after the transfer, as manifested by the studies of Raman, X-ray and ultraviolet photoemission spectroscopy (XPS and UPS), optical absorption, and sheet resistance. Additionally, XPS, UPS and optical absorption studies of fully graphene-covered CH_3NH_3PbI_3 thin films showed spectral invariance even after 3 months, which was in sharp contrast to the drastic spectral changes after merely one week in control CH_3NH_3PbI_3 samples without graphene protection. This successful demonstration of the graphene-enabled passivation and long-term stability of CH_3NH_3PbI_3 thin films therefore opens up a new pathway towards realistic photovoltaic applications of hybrid perovskites

Stabilization of hybrid perovskite CH_3NH_3PbI_3 thin films by graphene passivation

We report the long-term stability of water-sensitive hybrid perovskites CH_3NH_3PbI_3 that were protected with monolayer graphene. This successful passivation was enabled by our development of a new water-free and polymer-free graphene transfer method. Monolayer graphene samples grown by plasma-enhanced chemical vapor deposition and transferred onto different substrates with the water/polymer-free method were found to preserve their high-quality characteristics after the transfer, as manifested by the studies of Raman, X-ray and ultraviolet photoemission spectroscopy (XPS and UPS), optical absorption, and sheet resistance. Additionally, XPS, UPS and optical absorption studies of fully graphene-covered CH_3NH_3PbI_3 thin films showed spectral invariance even after 3 months, which was in sharp contrast to the drastic spectral changes after merely one week in control CH_3NH_3PbI_3 samples without graphene protection. This successful demonstration of the graphene-enabled passivation and long-term stability of CH_3NH_3PbI_3 thin films therefore opens up a new pathway towards realistic photovoltaic applications of hybrid perovskites

Construction and Evaluation of the Tumor-Targeting, Cell-Penetrating Multifunctional Molecular Probe iCREKA

A novel tumor stroma targeting and membrane-penetrating cyclic peptide, named iCREKA, was designed and labeled by fluorescein isothiocyanate (FITC) and positron emitter 18F to build the tumor-targeting tracers. The FITC-iCREKA was proved to have significantly higher cellular uptake in the glioma U87 cells in the presence of activated MMP-2 than that in absence of activated MMP-2 by cells fluorescence test in vitro. The tumor tissue fluorescence microscope imaging demonstrated that FITC-iCREKA accumulated in the walls of the blood vessels and the surrounding stroma in the glioma tumor at 1 h after intravenous injection. While at 3 h after injection, FITC-iCREKA was found to be uptaken in the tumor cells. However, the control FITC-CREKA can only be found in the tumor stroma, not in the tumor cells, no matter at 1 h or 3 h after injection. The whole-animal fluorescence imaging showed that the glioma tumor could be visualized clearly with high fluorescence signal. The microPET/CT imaging further demonstrated that 18F-iCREKA could target U87MG tumor in vivo from 30 min to 2 h after injection. The present study indicated the iCREKA had the capacity of tumor stroma targeting and the membrane-penetrating. It was potential to be developed as the fluorescent and PET tracers for tumor imaging

Exponential ATP amplification through simultaneous regeneration from AMP and pyrophosphate for luminescence detection of bacteria

a b s t r a c t Bacteria monitoring is essential for many industrial manufacturing processes, particularly those involving in food, biopharmaceuticals, and semiconductor production. Firefly luciferase ATP luminescence assay is a rapid and simple bacteria detection method. However, the detection limit of this assay for Escherichia coli is approximately 10 4 colony-forming units (CFU), which is insufficient for many applications. This study aims to improve the assay sensitivity by simultaneous conversion of PP i and AMP, two products of the luciferase reaction, back to ATP to form two chain-reaction loops. Because each consumed ATP continuously produces two new ATP molecules, this approach can achieve exponential amplification of ATP. Two consecutive enzyme reactions were employed to regenerate AMP into ATP: adenylate kinase converting AMP into ADP using UTP as the energy source, and acetate kinase catalyzing acetyl phosphate and ADP into ATP. The PP i -recycling loop was completed using ATP sulfurylase and adenosine 5 0 phosphosulfate. The modification maintains good quantification linearity in the ATP luminescence assay and greatly increases its bacteria detection sensitivity. This improved method can detect bacteria concentrations of fewer than 10 CFU. This exponential ATP amplification assay will benefit bacteria monitoring in public health and manufacturing processes that require high-quality water. Ó 2011 Elsevier Inc. All rights reserved. Bacteria monitoring is essential for many industrial manufacturing processes, and particularly those involving food, semiconductors, and biopharmaceuticals. The presence of bacteria reduces production yield and may cause serious health problems in humans. Researchers have developed several rapid assays for detecting bacteria in water. These methods include polymerase chain reactions, fluorescence in situ hybridization [1], b-D-glucuronidase activity measurement The ATP luminescence assay is a rapid, sensitive, and easy-toperform method based on the detection of ATP, a molecule ubiquitously present in all living cells. The enzyme luciferase catalyzes the oxidation of the substrate luciferin while transforming the energy derived from ATP into light, which can be quantified by a luminometer. This assay has been widely used in bacteria monitoring for food hygiene [4] and surface cleanliness The current detection limit of the ATP luminescence method for Escherichia coli is approximately 10 4 colony-forming units (CFU) 1 [12,13], which is not sensitive enough for many industrial and medical applications. Several approaches have been adopted to improve the assay sensitivity. The first strategy involves the identification of chemical extractants that can effectively disrupt bacterial cells while not interfering with the luminescence assay. Both dimethyl sulfoxide (DMSO) 0003-2697/$ -see front matter