A likely pathogenic variant putatively affecting splicing of PIGA identified in a multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2) family pedigree via whole-exome sequencing.

Background: Glycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively. More than 10 PIGA pathogenic or likely pathogenic variants have been reported in a wide spectrum of clinical syndromes of PIGA deficiency, including multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2).

The chemical identity, state and structure of catalytically active centers during the electrochemical CO reduction on porous Fe-nitrogen-carbon (Fe-N-C) materials.

We report novel structure-activity relationships and explore the chemical state and structure of catalytically active sites under conditions during the electrochemical CO reduction reaction (CORR) catalyzed by a series of porous iron-nitrogen-carbon (FeNC) catalysts. The FeNC catalysts were synthesized from different nitrogen precursors and, as a result of this, exhibited quite distinct physical properties, such as BET surface areas and distinct chemical N-functionalities in varying ratios. The chemical diversity of the FeNC catalysts was harnessed to set up correlations between the catalytic CORR activity and their chemical nitrogen-functionalities, which provided a deeper understanding between catalyst chemistry and function.

Asiatic acid enhances intratumor delivery and the antitumor effect of pegylated liposomal doxorubicin by reducing tumor-stroma collagen.

Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS. In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen, colon cancer xenograft mice (SW620 cell line) were treated by PLD, AA, or combined regimes, respectively; the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining; the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis.

Intergenerational transmission of interpersonal strengths: The role of parent gender, family processes, and child characteristics.

Interpersonal strengths are important positive traits of human beings. This study investigated the phenomenon and mechanisms of the intergenerational transmission of interpersonal strengths. A total of 992 fourth-to ninth-grade children (48.

Lewis-Basic Lanthanide Metal-Organic Framework-Derived Versatile Multi-Active-Site Synergistic Catalysts for Oxygen Reduction Reaction.

Oxygen reduction reaction underpins the development of the whole fuel-cell field, where there is a strong impetus to develop efficient and stable catalysts that can replace the precious metal Pt/C. Herein, a series of excellent catalysts for ORR derived from Ce/La dual lanthanide metal-organic framework with functional Lewis-basic sites were synthesized for the first time. The synergistic effect of high concentration of oxygen vacancies from La-embedded CeO and Fe-N sites as well as porous structure endows the catalyst superior performance to Pt/C, with a half-wave potential ( E) of 0.

Pharmacokinetic/Pharmacodynamic Analysis of Isavuconazole Against Aspergillus spp. and Candida spp. in Healthy Subjects and Patients With Hepatic or Renal Impairment by Monte Carlo Simulation.

The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study is to evaluate the efficacy of various isavuconazole dosing regimens for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamics (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (AUC/MIC) targets of isavuconazole.

Photocatalytic acylarylation of unactivated alkenes with diaryliodonium salts toward indanones and related compounds.

A novel photocatalytic acylarylation of unactivated alkenes using diaryliodonium salts as the arylation reagent is described. The reaction produces a variety of 2-benzyl indanones, 3,4-dihydronaphthalen-1(2H)-ones, and 2,3-dihydroquinolin-4(1H)-ones in promising yields with excellent diastereoselectivity under very mild conditions, which may be appealing for the synthesis of biologically active molecules.

Copper-catalyzed remote oxidation of alcohols initiated by radical difluoroalkylation of alkenes: facile access to difluoroalkylated carbonyl compounds.

A Cu-catalyzed oxidation of alcohols triggered by the radical difluoroalkylation of alkenes has been developed, providing facile access to a series of difluoroalkylated ketones or aldehydes in moderate to high yields. The concurrent realization of the catalytic oxidation of alcohols and difluoroalkylation of alkenes enables a highly efficient and attractive method for organic synthesis.

Target-Induced Horseradish Peroxidase Deactivation for Multicolor Colorimetric Assay of Hydrogen Sulfide in Rat Brain Microdialysis.

Hydrogen sulfide (HS) is important for normal neural functions, which involves protecting neurons from oxidative stress and neuronal transmission modulation in brain. The detection of HS is significant for revealing its role in the diagnosis of various disease. In this study, a novel multicolor colorimetric assay based on the etching of gold nanorods (Au NRs) is proposed to evaluate HS level with the naked eye.

Effect of hypoglycemic agents on survival outcomes of lung cancer patients with diabetes mellitus: A meta-analysis.

Background: To assess the association between hypoglycemic agents and prognosis of lung cancer patients with diabetes.

Methods: A comprehensive literature search was performed in PubMed, Web of Science, Embase, and Cochrane Library until May 2017. The search yielded 2593 unique citations, of which 18 articles met inclusion criteria.

Treatment of Refractory Idiopathic Supraorbital Neuralgia Using Percutaneous Pulsed Radiofrequency.

Background And Aims: No ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks. Pulsed radiofrequency is a neuromodulation technique that does not produce sequelae of nerve damage after treatment. However, the efficacy of percutaneous pulsed radiofrequency for the treatment of refractory idiopathic supraorbital neuralgia is still not clear.

Effects of metformin on survival outcomes of pancreatic cancer patients with diabetes: A meta-analysis.

Pancreatic cancer risk is reduced by metformin treatment in patients with diabetes. However, the effect of metformin on pancreatic cancer overall survival is unclear. The aim of the present study was to determine the association between metformin and clinical outcomes of pancreatic cancer patients with diabetes.

Homogeneous and label-free electrochemiluminescence aptasensor based on the difference of electrostatic interaction and exonuclease-assisted target recycling amplification.

The difference of electrostatic interaction between free Ru(phen) and Ru(phen) embedded in double strand DNA (dsDNA) to the negatively charged indium tin oxide (ITO) electrode has been applied to develop a homogeneous and label-free electrochemiluminescence (ECL) aptasensor for the first time. Ochratoxin A (OTA) has been chosen as the model target. The OTA aptamer is first hybridized with its complementary single strand DNA (ssDNA) to form dsDNA and then interacted with Ru(phen) via the grooves binding mode to form dsDNA-Ru(phen) complex, which remains negatively charged feature as well as low diffusion capacity to the negatively charged ITO electrode surface owing to the electrostatic repulsion.

Effect of Oridonin on Cytochrome P450 Expression and Activities in HepaRG Cell.

Oridonin, the major terpene found in Rabdosia rubescens, is widely used as a dietary supplement or therapeutic drug. However, the effects of oridonin on major CYP450s are still unclear. As oridonin can enhance the effect of other clinical drugs, in this study, we investigated the influence of oridonin on CYP450s mRNA expression and its impact on activities in human HepaRG cell to evaluate the safety by studying its potential drug interaction.

Pulsed Radiofrequency Improves Neuropathic Pain in Chronic Constriction Injury Rats through the Upregulation of the Transcription and Translation Levels of Glial Cell Line-Derived Neurotrophic Factor.

Background: Several studies in recent years have confirmed that the direct application of pulsed radiofrequency (PRF) on peripheral nerve compression points can alleviate hyperalgesia in animal models of neuropathic pain (NP). However, the mechanism underlying the treatment of peripheral nerves by PRF is unclear.

Objectives: We aim to observe changes in pain behavior after the application of PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic constriction injury (CCI) and to investigate the effects of PRF on the transcription and translation levels of glial cell line-derived neurotrophic factor (GDNF) in nerve tissues at the treatment site.

Pulsed Radiofrequency Applied to the Sciatic Nerve Improves Neuropathic Pain by Down-regulating The Expression of Calcitonin Gene-related Peptide in the Dorsal Root Ganglion.

Clinical studies have shown that applying pulsed radiofrequency (PRF) to the neural stem could relieve neuropathic pain (NP), albeit through an unclear analgesic mechanism. And animal experiments have indicated that calcitonin gene-related peptide (CGRP) expressed in the dorsal root ganglion (DRG) is involved in generating and maintaining NP. In this case, it is uncertain whether PRF plays an analgesic role by affecting CGRP expression in DRG.

A Nanocrystalline POM@MOFs Catalyst for the Degradation of Phenol: Effective Cooperative Catalysis by Metal Nodes and POM Guests.

Crystalline POM@MOFs hybrids are very promising for catalysis, due to catalytically active polyoxometalates (POMs) dispersed at the molecular level, and enhanced stability of both POMs and metal-organic frameworks (MOFs). Herein, PW was encapsulated into MOF HKUST-1 through a facile liquid-assisted grinding method, and the obtained [Cu (BTC) (H O) ] [HPW O ] (BTC=1,2,3-benzenetricarboxylic acid) nanocrystals (NENU-3N) were applied as catalysts in the degradation of phenol. It is the first time that liquid-assisted grinding was applied in the preparation of nanocrystalline POM@MOFs hybrids.

Highly sensitive colorimetric aptasensor for ochratoxin A detection based on enzyme-encapsulated liposome.

A simple, low-cost, and sensitive liposome-based colorimetric aptasensor has been developed to detect ochratoxin A (OTA). Specifically, a dumbbell-shaped probe was designed, including magnetic beads (MBs), double-stranded DNA (dsDNA), and enzyme-encapsulated liposome. The dsDNA formed by the hybridization between OTA aptamer and its complementary probe.

Screening of Sceptridium ternatum for antitussive and antiasthmatic activity and associated mechanisms.

Objectives Sceptridium ternatum is an expectorant in traditional Chinese medicine and is prescribed for the treatment of asthma. The study aim was to screen Sceptridium ternatum for ingredients with antitussive and antiasthmatic effects and to study their associated mechanisms. Methods Cough in mice was induced using ammonia.

A Simple and Convenient Aptasensor for Protein Using an Electronic Balance as a Readout.

The electronic balance, one of the most common pieces of equipment in the laboratory, is normally used to directly measure the weight of a target with high accuracy. However, little attention has been paid to the extension of its applications. In this study, an electronic balance was used as a readout to develop a novel aptasensor for protein quantification for the first time.

Invasive versus non-invasive ventilation for acute respiratory failure in neuromuscular disease and chest wall disorders.

Background: Acute respiratory failure is a common life-threatening complication of acute onset neuromuscular diseases, and may exacerbate chronic hypoventilation in patients with neuromuscular disease or chest wall disorders. Standard management includes oxygen supplementation, physiotherapy, cough assistance, and, whenever needed, antibiotics and intermittent positive pressure ventilation. Non-invasive mechanical ventilation (NIV) via nasal, buccal or full-face devices has become routine practice in many centres.

Association of extracellular superoxide dismutase (EC-SOD) polymorphisms with risk of type 2 diabetes mellitus in a Chinese Han population.

We aimed to investigate whether the EC-SOD rs2536512, rs8192291 and rs1799895 polymorphisms and haplotypes are associated with T2DM in a Chinese Han population. A total of 540 Chinese Han patients with T2DM and 562 healthy subjects were enrolled in our study since October 2013, and all of them had no blood relationship. An iPlex GLOD SNP genotyping analysis of the EC-SOD rs2536512, rs8192291 and rs1799895 was carried out in a 384 well plate format using the Sequenom MassARRAY System (Sequenom, Inc.

Stimulus-response click chemistry based aptamer-functionalized mesoporous silica nanoparticles for fluorescence detection of thrombin.

In most aptamer based stimulus response mesoporous silica nanoparticles (MSN) systems, the aptamer is modified on the MSN via electrostatic interaction, however leakage might exist after a certain time in the system and hence the stability is not good. In this study, the pores of MSN were capped by aptamer through click chemistry reaction for the first time and the system was then employed to develop a fluorescence biosensor. Specifically, the aptamer of the target (thrombin in this study) was hybridized with its complementary DNA (which was initially modified with alkyne at the terminal) to form a double strand DNA (dsDNA) firstly, and then this dsDNA was modified on N modified MSN via Cu(I) catalyzed alkyne-azide cycloaddition reaction.

Preparation of an Efficient Ratiometric Fluorescent Nanoprobe (m-CDs@[Ru(bpy)]) for Visual and Specific Detection of Hypochlorite on Site and in Living Cells.

Hypochlorite (ClO) is one of the most important reactive oxygen species (ROS), which plays an important role in sustaining human innate immunity during microbial invasion. Moreover, ClO is a powerful oxidizer for water treatment. The safety of drinking water is closely related to its content.

HIF-2α activated lncRNA NEAT1 promotes hepatocellular carcinoma cell invasion and metastasis by affecting the epithelial-mesenchymal transition.

The aim of this study was to investigate the role of NEAT1 in hepatocellular carcinoma (HCC), and probe whether NEAT1 participate in the epithelial-mesenchymal transition (EMT) and metastasis regulated by HIF-2α. Expression of lncRNA NEAT1 was initially assessed in HCC tissues and in a series of HCC cell lines. The correlations between NEAT1 levels and HIF-2α were analyzed through plasmid vector construction.