Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.

Purpose: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis.

Materials And Methods: Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013.

Subcutaneous Nanodisc Vaccination with Neoantigens for Combination Cancer Immunotherapy.

While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors.

Controlling Heat Transport and Flow Structures in Thermal Turbulence Using Ratchet Surfaces.

In this combined experimental and numerical study on thermally driven turbulence in a rectangular cell, the global heat transport and the coherent flow structures are controlled with an asymmetric ratchetlike roughness on the top and bottom plates. We show that, by means of symmetry breaking due to the presence of the ratchet structures on the conducting plates, the orientation of the large scale circulation roll (LSCR) can be locked to a preferred direction even when the cell is perfectly leveled out. By introducing a small tilt to the system, we show that the LSCR orientation can be tuned and controlled.

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.

A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers.

Purpose: Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD) are metabolic diseases with multisystem manifestations. Individuals with PBD-ZSD exhibit impaired peroxisomal biochemical functions and have abnormal levels of peroxisomal metabolites, but the broader metabolic impact of peroxisomal dysfunction and the utility of metabolomic methods is unknown.

Methods: We studied 19 individuals with clinically and molecularly characterized PBD-ZSD.

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.

Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Background: The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH).

Methods: Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity.

Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model.

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood-brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.

Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis.

Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-β1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators.

Mass and Moment of Inertia Govern the Transition in the Dynamics and Wakes of Freely Rising and Falling Cylinders.

In this Letter, we study the motion and wake patterns of freely rising and falling cylinders in quiescent fluid. We show that the amplitude of oscillation and the overall system dynamics are intricately linked to two parameters: the particle's mass density relative to the fluid m^{*}≡ρ_{p}/ρ_{f} and its relative moment of inertia I^{*}≡I_{p}/I_{f}. This supersedes the current understanding that a critical mass density (m^{*}≈0.

Grafting Modification of the Reactive Core-Shell Particles to Enhance the Toughening Ability of Polylactide.

In order to overcome the brittleness of polylactide (PLA), reactive core-shell particles (RCS) with polybutadiene as core and methyl methacrylate-co-styrene-co-glycidyl methacrylate as shell were prepared to toughen PLA. Tert-dodecyl mercaptan (TDDM) was used as chain transfer agent to modify the grafting properties (such as grafting degree, shell thickness, internal and external grafting) of the core-shell particles. The introduction of TDDM decreased the grafting degree, shell thickness and the T of the core phase.

Surface Energy and Surface Stability of Ag Nanocrystals at Elevated Temperatures and Their Dominance in Sublimation-Induced Shape Evolution.

The surface energy and surface stability of Ag nanocrystals (NCs) are under debate because the measurable values of the surface energy are very inconsistent, and the indices of the observed thermally stable surfaces are apparently in conflict. To clarify this issue, a transmission electron microscope is used to investigate these problems in situ with elaborately designed carbon-shell-capsulated Ag NCs. It is demonstrated that the {111} surfaces are still thermally stable at elevated temperatures, and the victory of the formation of {110} surfaces over {111} surfaces on the Ag NCs during sublimation is due to the special crystal geometry.

Ranking Businesses and Municipal Locations by Spatiotemporal Cardiac Arrest Risk to Guide Public Defibrillator Placement.

Background: Efforts to guide automated external defibrillator placement for out-of-hospital cardiac arrest (OHCA) treatment have focused on identifying broadly defined location categories without considering hours of operation. Broad location categories may be composed of many businesses with varying accessibility. Identifying specific locations for automated external defibrillator deployment incorporating operating hours and time of OHCA occurrence may improve automated external defibrillator accessibility.

Characterization of left ventricle energy loss in healthy adults using vector flow mapping: Preliminary results.

Background: Energy loss (EL) is a new quantitative hemodynamic index based on vector flow mapping (VFM). This study aimed to characterize EL of the left ventricle (LV) in healthy adults.

Methods: Fifty-one healthy adults were enrolled in this study.

FGF21 Is an Exocrine Pancreas Secretagogue.

The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho.

Strong Bioinspired Polymer Hydrogel with Tunable Stiffness and Toughness for Mimicking the Extracellular Matrix.

Inspired by the delicate architecture of hyaline articular cartilage, we report on a biomimetic polymer hydrogel that incorporates strong intermolecular hydrogen bonding between urethane-urethane linkages as well as urethane-ester linkages. The resultant hydrogel, containing ≈75% water, can endure a compressive stress up to 56 MPa with a strain of 98%, and exhibit tunable compressive modulus (0.19-1.

3D spherical-cap fitting procedure for (truncated) sessile nano- and micro-droplets & -bubbles.

In the study of nanobubbles, nanodroplets or nanolenses immobilised on a substrate, a cross-section of a spherical cap is widely applied to extract geometrical information from atomic force microscopy (AFM) topographic images. In this paper, we have developed a comprehensive 3D spherical-cap fitting procedure (3D-SCFP) to extract morphologic characteristics of complete or truncated spherical caps from AFM images. Our procedure integrates several advanced digital image analysis techniques to construct a 3D spherical-cap model, from which the geometrical parameters of the nanostructures are extracted automatically by a simple algorithm.

Highly Stretchable and Notch-Insensitive Hydrogel Based on Polyacrylamide and Milk Protein.

Protein-based hydrogels have received attention for biomedical applications and tissue engineering because they are biocompatible and abundant. However, the poor mechanical properties of these hydrogels remain a hurdle for practical use. We have developed a highly stretchable and notch-insensitive hydrogel by integrating casein micelles into polyacrylamide (PAAm) networks.

Mutations in TBL1X Are Associated With Central Hypothyroidism.

Context: Isolated congenital central hypothyroidism (CeH) can result from mutations in TRHR, TSHB, and IGSF1, but its etiology often remains unexplained. We identified a missense mutation in the transducin β-like protein 1, X-linked (TBL1X) gene in three relatives diagnosed with isolated CeH. TBL1X is part of the thyroid hormone receptor-corepressor complex.

Bubble Drag Reduction Requires Large Bubbles.

In the maritime industry, the injection of air bubbles into the turbulent boundary layer under the ship hull is seen as one of the most promising techniques to reduce the overall fuel consumption. However, the exact mechanism behind bubble drag reduction is unknown. Here we show that bubble drag reduction in turbulent flow dramatically depends on the bubble size.

Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study.

Background And Purpose: The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus.

Materials And Methods: Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study.

Advanced-Stage Nasopharyngeal Carcinoma: Restaging System after Neoadjuvant Chemotherapy on the Basis of MR Imaging Determines Survival.

Purpose To evaluate the prognostic value of the restaging system after neoadjuvant chemotherapy (NACT) in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and Methods This study was approved by the clinical research committee and a written informed consent was required before enrolling in the study. Prospectively enrolled were 412 consecutive patients with stage III-IVb NPC treated with NACT followed by concurrent chemotherapy and radiation therapy.

Metabolomic Profiling of Human Urine as a Screen for Multiple Inborn Errors of Metabolism.

Aims: We wished to determine the efficacy of using urine as an analyte to screen for a broad range of metabolic products associated with multiple different types of inborn errors of metabolism (IEMs), using an automated mass spectrometry-based assay. Urine was compared with plasma samples from a similar cohort analyzed using the same assay. Specimens were analyzed using two different commonly utilized urine normalization methods based on creatinine and osmolality, respectively.

Microbubbles and Microparticles are Not Faithful Tracers of Turbulent Acceleration.

We report on the Lagrangian statistics of acceleration of small (sub-Kolmogorov) bubbles and tracer particles with Stokes number St≪1 in turbulent flow. At a decreasing Reynolds number, the bubble accelerations show deviations from that of tracer particles; i.e.