Fatigue fracture of nearly elastic hydrogels.

Polyacrylamide hydrogels are highly stretchable and nearly elastic. Their stress-stretch curves exhibit small hysteresis, and change negligibly after many loading cycles. Polyacrylamide is used extensively in applications, and is the primary network for many types of tough hydrogels.

New directions in health sciences libraries in China.

This article briefly describes the services provided by Chinese health science libraries and the factors which influence service provision. Driven by new technologies and national initiatives, the key services delivered by Chinese health libraries in the last 10 years have been research support services (such as research impact assessment, support for data management), evidence-based medicine, systematic reviews, the promotion of health information literacy, and the development of institutional repositories. J.

Neoadjuvant PD-1 Blockade in Resectable Lung Cancer.

Background: Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade.

Methods: In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose.

Health Care Costs After Cardiac Arrest in the United States.

Background: This study was designed to estimate the costs of index hospitalizations after cardiac arrest in the United States.

Methods And Results: We used the US Nationwide Inpatient Sample (2003-2012) to identify patients with cardiac arrest. Log transformation of inflation-adjusted cost was determined for care to patient outcomes.

Distinct transcriptomic and exomic abnormalities within myelodysplastic syndrome marrow cells.

To provide biologic insights into mechanisms underlying myelodysplastic syndromes (MDS) we evaluated the CD34 marrow cells transcriptome using high-throughput RNA sequencing (RNA-Seq). We demonstrated significant differential gene expression profiles (GEPs) between MDS and normal and identified 41 disease classifier genes. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable versus patients who transformed into acute myeloid leukemia within 12 months.

Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter: A Multicenter, Randomized, Controlled Clinical Trial (PARAT).

Background And Purpose: Although flow diverters have been reported with favorable clinical and angiographic outcomes in various literatures, randomized trials determining their true effectiveness and safety are still in lack. The Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter (PARAT) trial was designed to evaluate the safety and efficacy of the Tubridge flow diverter in the treatment of large or giant aneurysms in comparison with Enterprise stent-assisted coiling.

Materials And Methods: This prospective, multicenter, randomized trial was conducted at 12 hospitals throughout China.

Time-Resolved In Situ Liquid-Phase Atomic Force Microscopy and Infrared Nanospectroscopy during the Formation of Metal-Organic Framework Thin Films.

Metal-organic framework (MOF) thin films show unmatched promise as smart membranes and photocatalytic coatings. However, their nucleation and growth resulting from intricate molecular assembly processes are not well understood yet are crucial to control the thin film properties. Here, we directly observe the nucleation and growth behavior of HKUST-1 thin films by real-time in situ AFM at different temperatures in a Cu-BTC solution.

Quadruple H-Bonding Cross-Linked Supramolecular Polymeric Materials as Substrates for Stretchable, Antitearing, and Self-Healable Thin Film Electrodes.

Herein, we report a de novo chemical design of supramolecular polymer materials (SPMs-1-3) by condensation polymerization, consisting of (i) soft polymeric chains (polytetramethylene glycol and tetraethylene glycol) and (ii) strong and reversible quadruple H-bonding cross-linkers (from 0 to 30 mol %). The former contributes to the formation of the soft domain of the SPMs, and the latter furnishes the SPMs with desirable mechanical properties, thereby producing soft, stretchable, yet tough elastomers. The resulting SPM-2 was observed to be highly stretchable (up to 17 000% strain), tough (fracture energy ∼30 000 J/m), and self-healing, which are highly desirable properties and are superior to previously reported elastomers and tough hydrogels.

Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and Atherogenesis.

Background: The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) showed that antagonism of interleukin (IL)-1β reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk. IL-1β and IL-18 are produced via the NLRP3 inflammasome in myeloid cells in response to cholesterol accumulation, but mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear. The cholesterol transporters ATP binding cassette A1 and G1 (ABCA1/G1) mediate cholesterol efflux to high-density lipoprotein, and Abca1/g1 deficiency in myeloid cells leads to cholesterol accumulation.

Targeting hepatic glutaminase activity to ameliorate hyperglycemia.

Glucagon levels increase under homeostatic, fasting conditions, promoting the release of glucose from the liver by accelerating the breakdown of glycogen (also known as glycogenolysis). Glucagon also enhances gluconeogenic flux, including from an increase in the hepatic consumption of amino acids. In type 2 diabetes, dysregulated glucagon signaling contributes to the elevated hepatic glucose output and fasting hyperglycemia that occur in this condition.

Coalescence driven self-organization of growing nanodroplets around a microcap.

The coalescence between growing droplets is important for the surface coverage and spatial arrangements of droplets on surfaces. In this work, total internal reflection fluorescence (TIRF) microscopy is utilized to in situ investigate the formation of nanodroplets around the rim of a polymer microcap, with sub-micron spatial and millisecond temporal resolution. We observe that the coalescence among droplets occurs frequently during their growth by solvent exchange.

Quantitative Arterial Tortuosity Suggests Arteriopathy in Children With Cryptogenic Stroke.

Background And Purpose: Quantitative arterial tortuosity (QAT) is a ratio of vessel length between 2 points to the shortest linear distance between same points. QAT has been reported as an imaging biomarker of arteriopathy in pediatric arterial ischemic stroke (AIS) because of dissection and transient cerebral arteriopathy. We sought to determine whether QAT abnormalities are present in other subtypes of pediatric AIS.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

Rationale: Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics.

Targeting ovarian cancer and endothelium with an allosteric PTP4A3 phosphatase inhibitor.

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways.

The Arabidopsis GORK K-channel is phosphorylated by calcium-dependent protein kinase 21 (CPK21), which in turn is activated by 14-3-3 proteins.

Potassium (K) is a vital ion for many processes in the plant and fine-tuned ion channels control the K-fluxes across the plasma membrane. GORK is an outward-rectifying K-channel with important functions in stomatal closure and in root K-homeostasis. In this study, post-translational modification of the Arabidopsis GORK ion channel and its regulation by 14-3-3 proteins was investigated.

Diffusive interaction of multiple surface nanobubbles: shrinkage, growth, and coarsening.

Surface nanobubbles are nanoscopic spherical-cap shaped gaseous domains on immersed substrates which are stable, even for days. After the stability of a single surface nanobubble has been theoretically explained, i.e.

Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy.

Cancer cells adapt to their inherently increased oxidative stress through activation of the glutathione (GSH) and thioredoxin (TXN) systems. Inhibition of both of these systems effectively kills cancer cells, but such broad inhibition of antioxidant activity also kills normal cells, which is highly unwanted in a clinical setting. We therefore evaluated targeting of the TXN pathway alone and, more specifically, selective inhibition of the cytosolic selenocysteine-containing enzyme TXN reductase 1 (TXNRD1).

Induction of microRNA-199 by Nitric Oxide in Endothelial Cells Is Required for Nitrovasodilator Resistance via Targeting of Prostaglandin I2 Synthase.

Background: Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by nitrate tolerance, because of the dysfunction of prostaglandin I2 synthase (PTGIS). MicroRNAs repress target gene expression and are recognized as important epigenetic regulators of endothelial function. The aim of this study was to determine whether nitrates induce nitrovasodilator resistance via microRNA-dependent repression of PTGIS gene expression.

Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens.

Human adenoviruses (HAdVs) are uniquely important "model organisms" as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens.

Targeted reduction of the EGFR protein, but not inhibition of its kinase activity, induces mitophagy and death of cancer cells through activation of mTORC2 and Akt.

The oncogenic epidermal growth factor receptor (EGFR) is commonly overexpressed in solid cancers. The tyrosine kinase activity of EGFR has been a major therapeutic target for cancer; however, the efficacy of EGFR tyrosine kinase inhibitors to treat cancers has been challenged by innate and acquired resistance at the clinic. Accumulating evidence suggests that EGFR possesses kinase-independent pro-survival functions, and that cancer cells are more vulnerable to reduction of EGFR protein than to inhibition of its kinase activity.

Differential Expression and Remodeling of Transient Outward Potassium Currents in Human Left Ventricles.

Background: Myocardial, transient, outward currents, , have been shown to play pivotal roles in action potential (AP) repolarization and remodeling in animal models. The properties and contribution of to left ventricular (LV) repolarization in the human heart, however, are poorly defined.

Methods And Results: Whole-cell, voltage-clamp recordings, acquired at physiological (35°C to 37°C) temperatures, from myocytes isolated from the LV of nonfailing human hearts identified 2 distinct transient currents, () and (), with significantly (<0.

Maintenance of Ideal Cardiovascular Health and Coronary Artery Calcium Progression in Low-Risk Men and Women in the Framingham Heart Study.

Background: Ideal cardiovascular health (CVH) is associated with a lower risk of cardiovascular disease and freedom from coronary artery calcium (CAC). Prospective data on the association between maintenance of optimal CVH and the progression of subclinical coronary atherosclerosis are limited. We assessed the influence of unfavorable versus favorable CVH on the incidence of CAC progression.

Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial.

To perform real-time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection. Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy for WGS and RNASeq.

Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat.

Background And Purpose: The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway.

Methods: SAH was induced by endovascular perforation in male Sprague-Dawley rats.

Vascular Semaphorin 7A Upregulation by Disturbed Flow Promotes Atherosclerosis Through Endothelial β1 Integrin.

Objective: Accumulating evidence suggests a role of semaphorins in vascular homeostasis. Here, we investigate the role of Sema7A (semaphorin 7A) in atherosclerosis and its underlying mechanism.

Approach And Results: Using genetically engineered mice, we showed that deletion of Sema7A attenuates atherosclerotic plaque formation primarily in the aorta of mice on a high-fat diet.