Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.

Background: Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.

Physicochemical characterization, antioxidant and anticancer activities of proteins from four legume species.

The physicochemical, functional, antioxidant and anticancer properties of protein isolates from the seeds of Soybean (SP), Black soybean (BSP), Adzuki bean (ABP), and Mung bean (MBP) were comparatively characterized. The difference was found in the protein composition and physicochemical properties of the four types of legume proteins, which affected the functional properties and bioactivities. BSP and SP had six predominant proteins with a molecular weight (M) range of 20-95 kDa, whereas ABP and MBP showed the most intense bands of 48 kDa.

Structural Characterization and Antifatigue Effect In Vivo of Maca (Lepidium meyenii Walp) Polysaccharide.

Maca (Lepidium meyenii Walp) polysaccharides (MP) with purity of 99.2% were obtained to investigate their structural characteristics and antifatigue effect in vivo. The physicochemical properties of MP were analyzed through high-performance gel filtration chromatography, IR, monosaccharide composition, methylation, GC-MS, and NMR analyses.

Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction: Implications for Cardiovascular Drug Discovery.

Background: Genome-wide association studies identified the association of the genetic locus (which encodes the chemokine CXCL12, also known as stromal cell-derived factor 1) with coronary artery disease and myocardial infarction (MI). Unlike CXCR4, the classic receptor for CXCL12, the function of CXCR7 (the most recently identified receptor) in vascular responses to injury and in MI remains unclear.

Methods: Tissue expression of CXCR7 was examined in arteries from mice and humans.

A multi-stimuli responsive nanoparticulate SN38 prodrug for cancer chemotherapy.

Modification of drug delivery systems (DDSs) with stimuli-responsive elements could significantly increase the tumor-specific delivery of anticancer drugs. Herein we synthesized a novel multiple stimuli-responsive SN38 prodrug, named PEG-S-S-SN38, by conjugating PEG (M: 2000) and SN38 with disulfide bonds and carbonic ester linkages as linkers for efficient delivery of SN38. The amphiphilic PEG-S-S-SN38, with a high SN38 loading content, could self-assemble into nanoparticles (NPs) with a stable diameter of ∼73 nm.

Isolation, chemical characterization, and immunomodulatory activity of naturally acetylated hemicelluloses from bamboo shavings.

Bamboo shavings, the outer or intermediate layer of bamboo stems, are the bulk of by-products produced in bamboo processing. In this study we investigated the isolation, chemical characterization, and immunostimulatory activity in vitro of the hemicelluloses from bamboo shavings. Shavings were first pretreated by steam explosion.

Retinol-Binding Protein-Dependent Cholesterol Uptake Regulates Macrophage Foam Cell Formation and Promotes Atherosclerosis.

Background: Retinol-binding protein 4 (RBP4) is an adipokine that plays decisive roles in glucose metabolism and insulin sensitivity. Elevated circulating RBP4 levels were reported to be associated with increased risk for cardiovascular disease, but the precise role of RBP4 in atherosclerotic diseases and its mechanisms of action remain elusive.

Methods: Serum RBP4 levels of 1683 participants from South China were evaluated and the occurrence of major adverse cardiovascular events was followed up for 5 years.

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

Background: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

Synthesis of Poly(phenyltriazolylcarboxylate)s with Aggregation-Induced Emission Characteristics by Metal-Free 1,3-Dipolar Polycycloaddition of Phenylpropiolate and Azides.

Two soluble poly(phenyltriazolylcarboxylate)s (PPTCs) with high molecular weights (M up to 26 800) are synthesized by the metal-free 1,3-dipolar polycycloadditions of 4,4'-isopropylidenediphenyl diphenylpropiolate (1) and tetraphenylethene-containing diazides (2) in dimethylformamide at 150 °C for 12 h in high yields (up to 93%). The resultant polymers are soluble in common organic solvents and are thermally stable with 5% weight loss temperatures higher than 375 °C. The PPTCs are nonemissive in solutions, but become highly luminescent upon aggregation, showing a phenomenon of aggregation-induced emission.

Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

Background: Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes.

Methods: We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology.

Microwave-assisted synthesis, structure and anti-tumor activity of selenized Artemisia sphaerocephala polysaccharide.

In this work, selenylation of Artemisia sphaerocephala polysaccharide (SeASP) was studied by using HSeO/HNO/BaCl reaction system in microwave field. SeASP exhibited the Se content range of 111-264μg/g with high yields (72.1-94.

Sphallerocarpus gracilis polysaccharide protects pancreatic β-cells via regulation of the bax/bcl-2, caspase-3, pdx-1 and insulin signalling pathways.

In this study, the structural characterization of Sphallerocarpus gracilis polysaccharide (SGP) and its hypoglycaemic activities are reported for the first time. SGP, which has a weight average molar mass (M) of 7.413×10, was isolated from Sphallerocarpus gracilis and purified by ion-exchange chromatography.

RAFT-Polymerization-Induced Self-Assembly and Reorganizations: Ultrahigh-Molecular-Weight Polymer and Morphology-Tunable Micro-/Nanoparticles in One Pot.

A one-pot method is introduced for the successful synthesis of narrow-distributed (Đ = 1.22) vinyl polymer with both ultrahigh molecular weight (UHMW) (M = 1.31 × 10 g mol ) and micro-/nanomorphology under mild conditions.

Physicochemical and structural characteristics of the octenyl succinic ester of ginkgo starch.

The physicochemical and structural characteristics of octenyl succinate (OS)-starch prepared from ginkgo starch were investigated. The degree of substitution (DS) and reaction efficiency of 1.5 and 3.

Age-Associated Sirtuin 1 Reduction in Vascular Smooth Muscle Links Vascular Senescence and Inflammation to Abdominal Aortic Aneurysm.

Rationale: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown.

Quantifying the Cerebral Hemodynamics of Dural Arteriovenous Fistula in Transverse Sigmoid Sinus Complicated by Sinus Stenosis: A Retrospective Cohort Study.

Background And Purpose: Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas.

Core-shell stability of nanoparticles plays an important role for overcoming the intestinal mucus and epithelium barrier.

The hydrophilic and electro-neutral surfaces of nanoparticles (NPs) were generally reported to facilitate their intestinal mucus penetration. Meanwhile, this surface property may prevent the epithelial uptake of NPs by reducing their affinity with the target cell membrane. Our group previously reported a core-shell structure of NPs, in which a "mucus-inert" hydrophilic coating of N-(2-hydroxypropyl)methacrylamidecopolymer (pHPMA) facilitated the mucus permeation of the trimethyl chitosan NP core.

Heme Oxygenase-1/Carbon Monoxide-regulated Mitochondrial Dynamic Equilibrium Contributes to the Attenuation of Endotoxin-induced Acute Lung Injury in Rats and in Lipopolysaccharide-activated Macrophages.

Background: Sepsis-associated acute lung injury remains the major cause of mortality in critically ill patients and is characterized by marked oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics are indispensable for functional integrity. Additionally, heme oxygenase (HO)-1/carbon monoxide conferred cytoprotection against end-organ damage during endotoxic shock.

Integrin Imaging with Tc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non-Small Cell Lung Cancer.

Purpose To evaluate an integrin imaging approach based on single photon emission computed tomography (SPECT)/computed tomography (CT) by using technetium 99m (Tc)-dimeric cyclic arginine-glycine-aspartic acid (RGD) peptides with three polyethylene glycol spacers (3PRGD2) as the tracer to target the integrin αβ expression in lung cancer and lymph node metastasis. Materials and Methods With ethics committee approval and written informed consent, 65 patients (41 male, 24 female; mean age, 60 years ± 11 [standard deviation]) with suspicious lung lesions were recruited with informed consent. The patients underwent both Tc-3PRGD2 SPECT/CT and fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT within 1 week.

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

Background: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes.

Adaptive Randomization of Neratinib in Early Breast Cancer.

Background: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e.

Anti-hepatoma activity of the stiff branched β-d-glucan and effects of molecular weight.

The water soluble β-(1 → 3)-d-glucan with short branches (AF1) isolated from Auricularia auricula-judae was successfully fractionated by ultrasonication into three fractions with different weight-average molecular weights (Ms). The results of static and dynamic laser light scattering, viscometry and atomic force microscopy confirmed that the AF1 samples adopted a stiff chain conformation in water, and the coexistence of individuals and aggregates occurred gradually with increasing concentration. The AF1 sample with the highest M easily self-entangled, and exhibited a strong shear rate-dependence of viscosity in water.

Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications.

The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds.

Cascade degradation of organic matters in brewery wastewater using a continuous stirred microbial electrochemical reactor and analysis of microbial communities.

A continuous stirred microbial electrochemical reactor (CSMER), comprising of a complete mixing zone (CMZ) and microbial electrochemical zone (MEZ), was used for brewery wastewater treatment. The system realized 75.4 ± 5.

Oligoethylenimine grafted PEGylated poly(aspartic acid) as a macromolecular contrast agent: properties and in vivo studies.

PEGylated poly(aspartate-g-OEI) was developed as a magnetic resonance imaging probe. The PEG-PBLA block copolymer was prepared by the ring-opening polymerization of β-benzyl-l-aspartate N-carboxy-anhydride (BLA-NCA) initiated by the terminal primary amino group of mPEG-NH, followed by grafting with oligoethylenimine (OEI, M = 800) and Gd-DTPA. Compared to Gd-DTPA (4.