[Cloning and in vitro expression of XCR1 of Rhesus macaque].

Objective To characterize the gene of Rhesus macaque XC chemokine receptor 1 (XCR1) and express it in HEK293T cells. Methods Rhesus macaque XCR1 gene was amplified by reverse transcription PCR (RT-PCR) and rapid amplification of cDNA end (RACE). The sequence alignment was compared with XCR1 of other species in GenBank.

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor.

Background: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks.

Methods: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening.

T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma.

Rationale: Hypertension remains to be a global public health burden and demands novel intervention strategies such as targeting T cells and T-cell-derived cytokines. Mineralocorticoid receptor (MR) antagonists have been clinically used to treat hypertension. However, the function of T-cell MR in blood pressure (BP) regulation has not been elucidated.

Deficient Circumferential Growth Is the Primary Determinant of Aortic Obstruction Attributable to Partial Elastin Deficiency.

Objective: Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of , the gene encoding elastin. Lesions are thought to result primarily from excessive smooth muscle cell (SMC) proliferation and consequent medial expansion, although an initially smaller caliber and increased stiffness of the aorta may contribute to luminal narrowing. The relative contributions of such abnormalities to the obstructive phenotype had not been defined.

A neutral dinuclear Ir(iii) complex for anti-counterfeiting and data encryption.

A neutral dinuclear Ir(iii) Schiff base complex PIBIP has been synthesized and shown to exhibit both piezochromic luminescence (PCL) and aggregation induced emission (AIE) behaviour. An efficient second-level anti-counterfeit trademark and a data encryption device were fabricated using PIBIP as the active material.

Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

Background: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency.

Methods: We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial.

Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by progressive motor neuron loss and caused by mutations in (). The disease severity inversely correlates with the copy number of a duplicated gene that is nearly identical to We have delineated a mechanism of transcriptional regulation in the locus. A previously uncharacterized long noncoding RNA (lncRNA), (), represses expression by recruiting the Polycomb Repressive Complex 2 (PRC2) to its locus.

Long-Term Biased β-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy.

Background: Biased agonism of the angiotensin II receptor is known to promote cardiac contractility. Our laboratory indicated that these effects may be attributable to changes at the level of the myofilaments. However, these signaling mechanisms remain unknown.

Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II-Induced Aortic Aneurysm and Atherosclerosis.

Objective: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations.

Approach And Results: SOST protein was downregulated in human and mouse AA samples compared with controls.

Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin.

Accumulation of amyloid-β (Aβ) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of Aβ remains elusive although evidence suggests soluble oligomers may be primarily responsible for neurotoxicity. Crenezumab is a humanized anti-Aβ monoclonal IgG4 that binds multiple forms of Aβ, with higher affinity for aggregated forms, and that blocks Aβ aggregation, and promotes disaggregation.

Novel chemoimmunotherapeutic strategy for hepatocellular carcinoma based on a genome-wide association study.

Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression.

Stress-Activated Kinase Mitogen-Activated Kinase Kinase-7 Governs Epigenetics of Cardiac Repolarization for Arrhythmia Prevention.

Background: Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical proarrhythmic side effects, culminating in a greater risk of sudden death.

Methods: We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harboring mitogen-activated kinase kinase-7 knockout or overexpression.

[Sublethal effects of spinetoram and azadirachtin on development and reproduction of Frankliniella occidentalis (Pergande).].

To evaluate the sublethal effects of spinetoram and azadirachtin on western flower thrips, Frankliniella occidentalis, leaf dipping method was used to determine their sublethal concentrations (LC) on the 2 instar nymph, and their influences on development and reproduction of F. occidentalis were studied. The results showed exposure of sublethal concentrations of spinetoram and azadirachtin to F.

Colorimetric sensor for cysteine in human urine based on novel gold nanoparticles.

Herein, a novel, high sensitive, and specific colorimetric sensor for cysteine (Cys) based on pectinase protected gold nanoparticles (P@AuNPs) has been demonstrated for the first time. The P@AuNPs were synthesized by "MW-assisted heat method" and were characterized by UV-vis, TEM, FT-IR and zeta potential techniques. Cys could cause the aggregation of P@AuNPs due to formation of the strong covalent Au-S bond and electrostatic binding.

[Antigenic Characterization of Immunodominant Epitopes of Alpha-8 giardin in Giardia lamblia].

Objective: To identify the dominant epitopes of α-8 giardin in Giardia lamblia, and analyze their immunoreactivity.

Methods: Three dominant epitopes G1（7-17 aa）, G2（30-40 aa） and G3（296-306 aa） were predicted for α-8 giardin by bioinformatic analysis using DNAstar, Biosun and CLUSTAL W softwares. Each epitope was conjugated to keyhole limpethemocyanin (KLH) and then used to immunize female Chinchilla rabbits via multi-point（8-10 points） subcutaneous injections on the back（0.

Gallstones and Risk of Coronary Heart Disease: Prospective Analysis of 270 000 Men and Women From 3 US Cohorts and Meta-Analysis.

Objective: Gallstone disease has been related to cardiovascular risk factors; however, whether presence of gallstones predicts coronary heart disease (CHD) is not well established.

Approach And Results: We followed up 269 142 participants who were free of cancer and cardiovascular disease at baseline from 3 US cohorts: the Nurses' Health Study (112 520 women; 1980-2010), Nurses' Health Study II (112 919 women; 1989-2011), and the Health Professionals Follow-up Study (43 703 men; 1986-2010) and documented 21 265 incident CHD cases. After adjustment for potential confounders, the hazard ratio for the participants with a history of gallstone disease compared with those without was 1.

S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited.

Beneficial Role of Erythrocyte Adenosine A2B Receptor-Mediated AMP-Activated Protein Kinase Activation in High-Altitude Hypoxia.

Background: High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust to hypoxia may lead to pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation to high altitude may reveal novel therapeutics to counteract the detrimental consequences of hypoxia.

Genome-Scale Metabolic Model for the Green Alga Chlorella vulgaris UTEX 395 Accurately Predicts Phenotypes under Autotrophic, Heterotrophic, and Mixotrophic Growth Conditions.

The green microalga Chlorella vulgaris has been widely recognized as a promising candidate for biofuel production due to its ability to store high lipid content and its natural metabolic versatility. Compartmentalized genome-scale metabolic models constructed from genome sequences enable quantitative insight into the transport and metabolism of compounds within a target organism. These metabolic models have long been utilized to generate optimized design strategies for an improved production process.

[Prokaryotic Expression, Purification and Immunological Characterization of Micronemal Protein 16 of Toxoplama gondii].

Objective: To prokaryotically express three gene fragments of micronemal protein 16 （TgMIC16） of Toxoplasma gondii, and analyze the immunoreactivity of the three recombinant protein products.

Methods: Primers were designed for three fragments of TgMIC16 gene which encode proteins within the functional domain. Reverse-transcription PCR was used to generate cDNA from RNA, and the three fragments were amplified on the cDNA by PCR using the designed primers.

Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand.

Background: Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure.

Methods: We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection.

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits.

Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention.

Background: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention.

Methods And Results: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries.

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

Background: Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols.

Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media.

Context: Iodinated contrast media (ICM) is routinely used in imaging studies and contains several 100-fold the recommended daily allowance of iodine.

Objective: To determine whether children exposed to ICM have a higher risk of iodine-induced thyroid dysfunction.

Design: This was a single-institution case-control study, examining patients with incident thyroid dysfunction aged less than 18 years from 2001 to 2015.