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The present study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms in C57BL/6J mice fed with a high-fat diet (HFD).Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight and epididymal white adipose tissue (eWAT) weight without changing their food intake when compared with HFD group. The hyperlipidemia of HFD-fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipids content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD+ZIN-fed mice compared with HFD group. Furthermore, zingerone binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα) with an optimal docking energy of -7.31kJ/mol. Uncoupling protein 1 (UCP1), PPAR-γ coactivator-1α (PGC-1α) and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, compared to HFD fed mice. In addition, zingerone intake restructured the community composition of gut microbiota. In detail, the ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased.Zingerone can attenuate obesity and related symptoms in HFD-fed mice probably via the modulation of PPARα-thermogenesis-gut microbiota interactions. This article is protected by copyright. All rights reserved.

Emergency general surgery is an emerging public health issue globally, with substantial healthcare burden. Interhospital transfer of critically unwell surgical patients has been the mainstay of bridging gaps in surgical coverage in regional and rural locations, despite evidence of greater morbidity and mortality. Delays in transfer invariably occurs and compounds the situation. Our aim was to examine the factors influencing interhospital transfer delays in emergency general surgical patients.A systematic search of PubMED and EmBase, was performed by two researchers from 2020 to 23rd Feb 2021, for English articles related to interhospital transfer delays in emergency general surgical patients, with an age of16. Articles were critically appraised and data were extracted into a pre-specified data extraction form. No data was suitable for statistical analysis and a narrative synthesis was performed instead.Six relevant articles were identified from the search. All studies were retrospective cohort studies with moderate to high risk of bias. Lack of consultant surgeon input, after hours transfer, need for intensive care bed and poor transfer documentation may have a role in interhospital transfer delays. Patients with public health insurance, multiple comorbidities and non-emergency medical conditions experience longer transfer request time and may be at risk of precipitating interhospital transfer delays. Transfer delays are seen in transfers over longer distances.There is a paucity of knowledge on what and how factors influence interhospital transfer delays in emergency general surgical patients. Well-designed prospective cohort studies are required to bridge this knowledge gap.

We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one-pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3-amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N-protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di- and tri-substituted piperidines, which ranks the topmost frequent N-heterocycle in commercial drugs.

BACKGROUND & AIM The development of hepatocellular carcinoma (HCC) is associated with the formation of communication networks leading to the recruitment of disease-modifying macrophages. However, how oncogenes in tumour cells control paracrine communication is not fully understood. METHODS Transgenic mice with liver-specific expression of the constitutively active yes-associated protein (YAPS127A ) or an orthotopic implantation model served as tumour models. FACS-sorted F4/80+ /CD11bdim /CD146- /retinoid- macrophages from healthy and tumour-bearing livers were used for transcriptomic profiling. Expression data of 242 human HCCs and a tissue microarray consisting of 91 HCCs and seven liver tissues were analyzed. RESULTS Screening of primary tumour cells expressing YAPS127A identified CC chemokine ligand 2 (Ccl2) as a macrophage chemoattractant, whose expression was regulated in a YAP/TEA domain family member 4 (TEAD4)-dependent manner. Ccl2 expression was associated with a loss of Kupffer cells (KCs) and an increase in immature macrophages (Mɸimm ) in hepatocarcinogenesis. Recruited Mɸimm were characterized by a lack of functional polarization (M0 signature) and high expression of the Ccl2 receptors C-C motif chemokine receptor 2 (Ccr2), C-X3-C motif chemokine receptor 1 (Cx3cr1) and pro-angiogenic platelet-derived growth factors (Pdgfa/Pdgfb). Mɸimm formed cellular clusters in the perivascular space, which correlated with vascular morphometric changes indicative for angiogenesis. In human HCCs, the M0 signature served as an identifier for poor clinical outcome and CCL2 correlated with YAP expression and vascular network formation. CONCLUSIONS In conclusion, YAP/TEAD4-regulated Ccl2 associates with perivascular recruitment of unpolarized Mɸimm and may contribute to a proangiogenic microenvironment in liver cancer.

As a new environmentally friendly separation technology, deep eutectic solvent based aqueous two-phase systems are extensively applied in various fields. Herein, we review recent advances in this field and highlight the possible directions of future developments. This article focuses on the effects of deep eutectic solvent and inorganic salts on the phase equilibrium, the microstructure of deep eutectic solvent based aqueous two-phase systems, the applications of deep eutectic solvent based aqueous two-phase systems in separation (proteins, biopolymers, saponins, and organic acids), and removal and recovery technologies for deep eutectic solvent from aqueous two-phase systems.

Peptides have gained increased interest over the past several decades because of their therapeutics. In this research, a strategy combining MCI gel column chromatography and high-speed countercurrent chromatography was developed for the separation of high-purity peptide Val-Val-Tyr-Pro from Globin Peptide. First, the fraction of Val-Val-Tyr-Pro mixtures with a purity of 15.8% was obtained by using MCI gel column with a mixture of ethanol/water (20:80, v/v/v). Then, the high-purity Val-Val-Tyr-Pro was separated by high-speed countercurrent chromatography with a aqueous two phase systems of ethanol/acetonitrile/iso-propyl alcohol/(NH4 )2 SO4 Saturated solution /H2 O (0.5:0.5:0.25:1.5:0.7,v/v). The ammonium sulfate from high-speed countercurrent chromatography fractions was removed from target compound by MCI gel column chromatography using ethanol/water in stepwise elution mode. A 78 mg of Val-Val-Tyr-Pro was successfully purified with the purities of 98.80% from 30 g crude Globin Peptide. The amino acid sequence of the Val-Val-Tyr-Pro was determined by electrospray ionization high resolution tandem mass spectrometry. The method presents a practical strategy for the large-scale separation of pure peptide Val-Val-Tyr-Pro from Globin Peptide, and provides a reference method for obtaining high-purity peptide from other polypeptide mixtures.

Objective This study aimed to explore the effect of bronchopulmonary dysplasia (BPD) on the early intellectual development of preterm infants. Methods From 2011 to 2015, 83 preterm infants diagnosed with BPD were recruited to the BPD group, and 89 preterm infants without BPD and 98 healthy term infants were randomly recruited to the non-BPD and term group, respectively. Neural and intellectual development according to the Gesell Development Scale were evaluated and compared between groups at 0-3 months, 3-6 months, 6-9 months, and 9-12 months of adjusted age for preterm infants and real age for term infants. Multivariate logistic regression was used to determine the associations between BPD and adverse neurological outcomes at 9-12 months of adjusted age. Results Compared to term infants, preterm infants had significantly lower developmental quotients for adaptability, gross motor, fine motor, language and social intercourse skills. At follow-up, deficits in one or more neurofunctions related to adaptability, gross motor, fine motor, language and social intercourse skills were significantly more frequent in preterm children with BPD than in those with no history of BPD. BPD was independently associated with adverse neurological outcomes at 9-12 months of adjusted age in preterm infants. Conclusions Early intelligence disturbances occurred significantly more frequently in BPD infants than non-BPD infants. Monitoring of the development of the nervous system in BPD infants should be strengthened. This article is protected by copyright. All rights reserved.

Increased blood non-esterified fatty acid (NEFA) concentrations might be implicated as a factor that plays a role in the pathogenesis of gastrointestinal motility disorder, such as abomasal displacement. We sought to elucidate possible effects of high concentrations of NEFA on primary cultured bovine abomasal smooth muscle cells (BSMC). BSMC treated with high concentrations of NEFA resulted in decrease of cell viability and increase of cell apoptosis rate. NEFA treatment induced oxidative stress, as revealed by increased levels of ROS and MDA, while decreased the antioxidative abilities (SOD, CAT, GSH, and GSSG) in BSMC. Meanwhile, high concentrations of NEFA induced BSMC mitochondrial apoptotic cell death. Mitochondrial membrane potential decrease, increased Bax and decreased Bcl-2, cytochrome c release, caspases activation, and apoptosis inducing factor (AIF) translocation were observed in NEFA-treated cells. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these NEFA-induced events. In conclusion, these results show that NEFA induce BSMC apoptosis mainly via a ROS-dependent mechanism involving the mitochondrial pathway. The cytotoxicity of non-esterified fatty acid (consist of oleic acid, linoleic acid, palmitic acid, stearic acid, and palmitoleic acid) on primary cultured bovine abomasal smooth muscle cell, and the underlying molecular mechanism.

For eight-band LTE/WWAN operation (704–960/1710–2690 MHz) in the Ultrabook or thin-profile tablet computer, a planar antenna of simple structure and small size is presented. The proposed antenna is obtained by modifying a simple planar inverted-F antenna and can be printed on one surface of a thin FR4 substrate of size 10 × 45 mm2 only. The antenna's lower band bandwidth is greatly widened by embedding a proper chip capacitor of 2.7 pF at the feeding strip. This chip capacitor combines with the antenna's shorting strip can control the excitation of a parallel resonance to modify the impedance matching of the antenna's lower band such that a widened bandwidth is easily obtained to cover the LTE700/GSM850/900 operation. Conversely, the antenna's upper-band bandwidth is also greatly enhanced by using a coupled section in the antenna's radiating strip and adding a parasitic shorted strip near the feeding strip, which lead to multiple resonant modes excited to form a wide bandwidth (>1 GHz) to cover the GSM1800/1900/UMTS/LTE2300/2500 operation. Owing to its small size and simple structure, the proposed antenna is very suitable to be applied in achieving an antenna array with high isolation for MIMO or dual talk (dual WWAN) operation. Promising high-isolation antenna arrays formed by the proposed antennas are presented. The obtained isolation between the antennas in the antenna array is better than 12 dB, and the envelope correlation coefficient is less than 0.15 for frequencies over the LTE/WWAN bands. Details of the proposed antenna and antenna array are presented. © 2013 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:1928–1934, 2013

The biomaterials used for central nervous system injury require not only interacting with specific cell adhesion but also specific growth factor receptors to promote nerve regeneration. In this study, hyaluronic acid (HA)-based hydrogels modified with poly-L-lysine (PLL) and nogo-66 receptor antibody (antiNgR) (HA-PLL/antiNgR) were administered to rats after lateral hemisection of the spinal cord. Anti-neurofilament positive axons were found to extend into the HA-PLL/antiNgR hydrogel at 8 weeks after implantation, which shows significant difference compared with HA-PLL or blank control group. Electron micrographs of implanted hydrogels showed that there were more cells and normal axons with myelin in the HA-PLL/antiNgR implant than that of HA-PLL hydrogel. The antiNgR grafted on HA hydrogels could be detected for 8 weeks after transplantation in vivo. All of these properties may facilitate HA-PLL/antiNgR hydrogels to become a promising scaffold for repairing spinal cord injury. Nevertheless, both two kinds of modified hydrogels (HA-PLL/antiNgR and HA-PLL) showed remarkable advantages in supporting angiogenesis, and simultaneously inhibiting the formation of glial scar.

An efficient Lewis acid-assisted, iron-catalyzed amination of alcohols using borrowing hydrogen methodology was developed. In particular, silver fluoride was identified to be a highly effective additive to overcome the low efficiency in the amination of secondary alcohols catalyzed by Knolker's complex.

The benzylation of various primary, secondary and tertiary aliphatic alcohols as well as phenols proceeds smoothly with title benzyloxypyridinium triflate (II) under microwave irradiation.