Therapeutic Potential of Progranulin in Hyperhomocysteinemia-Induced Cardiorenal Dysfunction.

Hyperhomocysteinemia (hHcys) is an important independent risk factor for the development of cardiovascular disease and end-stage renal disease. Although multiple approaches lowering the levels of homocysteine have been used in experimental studies and clinical trials, there is no effective therapy available to fully prevent homocysteine-induced injury. Therefore, identifying key molecules in the pathogenic pathways may provide clues to develop new therapeutic strategies for the treatment of hHcys-associated injury beyond lowering the plasma homocysteine levels.

Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients.

Objective: We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial).

Approach And Results: After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.

In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients.

Context: Recently, two patients with primary ovarian insufficiency (POI) delivered healthy babies after in vitro activation (IVA) treatment followed by auto-transplantation of frozen-thawed ovarian tissues.

Objective: This study sought to report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in patients with POI, together with monitoring of follicle development and serum hormonal changes.

Design: This was a prospective observational cohort study.

Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients.

Background And Purpose: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial.

Methods: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone.

Antiphosphatidylserine Antibodies and Clinical Outcomes in Patients With Acute Ischemic Stroke.

Background And Purpose: Antiphosphatidylserine antibodies (aPS) have been associated with the risk of ischemic stroke. However, it remains unclear whether aPS will influence clinical outcomes in patients with acute ischemic stroke.

Methods: A total of 3013 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in the study The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke.

AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function.

Objective: Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical-actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress.

Approach And Results: Analysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation.

A MicroRNA302-367-Erk1/2-Klf2-S1pr1 Pathway Prevents Tumor Growth via Restricting Angiogenesis and Improving Vascular Stability.

Rationale: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367 cluster in angiogenesis and tumors has not yet been fully evaluated.

Objective: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases.

Association between Participation in an Intensive Longitudinal Assessment Program and Performance on a Cognitive Examination in the Maintenance of Certification in Anesthesiology Program®.

Background: As part of the Maintenance of Certification in Anesthesiology Program® (MOCA®), the American Board of Anesthesiology (Raleigh, North Carolina) developed the MOCA Minute program, a web-based intensive longitudinal assessment involving weekly questions with immediate feedback and links to learning resources. This observational study tested the hypothesis that individuals who participate in the MOCA Minute program perform better on the MOCA Cognitive Examination (CE) compared with those who do not participate.

Methods: Two separate cohorts of individuals eligible for July 2014 and January 2015 CEs were invited to participate in this pilot.

Mechatronic Development and Vision Feedback Control of a Nanorobotics Manipulation System inside SEM for Nanodevice Assembly.

Carbon nanotubes (CNT) have been developed in recent decades for nanodevices such as nanoradios, nanogenerators, carbon nanotube field effect transistors (CNTFETs) and so on, indicating that the application of CNTs for nanoscale electronics may play a key role in the development of nanotechnology. Nanorobotics manipulation systems are a promising method for nanodevice construction and assembly. For the purpose of constructing three-dimensional CNTFETs, a nanorobotics manipulation system with 16 DOFs was developed for nanomanipulation of nanometer-scale objects inside the specimen chamber of a scanning electron microscope (SEM).

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.

Independent and Joint Effect of Brachial-Ankle Pulse Wave Velocity and Blood Pressure Control on Incident Stroke in Hypertensive Adults.

Pulse wave velocity (PWV) has been shown to influence the effects of antihypertensive drugs in the prevention of cardiovascular diseases. Data are limited on whether PWV is an independent predictor of stroke above and beyond hypertension control. This longitudinal analysis examined the independent and joint effect of brachial-ankle PWV (baPWV) with hypertension control on the risk of first stroke.

Phosphorylation of a NAC Transcription Factor by a Calcium/Calmodulin-Dependent Protein Kinase Regulates Abscisic Acid-Induced Antioxidant Defense in Maize.

Calcium/calmodulin-dependent protein kinase (CCaMK) has been shown to play an important role in abscisic acid (ABA)-induced antioxidant defense and enhance the tolerance of plants to drought stress. However, its downstream molecular events are poorly understood. Here, we identify a NAC transcription factor, ZmNAC84, in maize (Zea mays), which physically interacts with ZmCCaMK in vitro and in vivo.

Two Redundant Receptor-Like Cytoplasmic Kinases Function Downstream of Pattern Recognition Receptors to Regulate Activation of SA Biosynthesis.

Salicylic acid (SA) serves as a critical signaling molecule in plant defense. Two transcription factors, SARD1 and CBP60g, control SA biosynthesis through regulating pathogen-induced expression of Isochorismate Synthase1, which encodes a key enzyme for SA biosynthesis. Here, we report that Pattern-Triggered Immunity Compromised Receptor-like Cytoplasmic Kinase1 (PCRK1) and PCRK2 function as key regulators of SA biosynthesis.

Modular design and development methodology for robotic multi-axis F/M sensors.

Accurate Force/Moment (F/M) measurements are required in many applications, and multi-axis F/M sensors have been utilized a wide variety of robotic systems since 1970s. A multi-axis F/M sensor is capable of measuring multiple components of force terms along x-, y-, z-axis (Fx, Fy, Fz), and the moments terms about x-, y- and z-axis (Mx, My and Mz) simultaneously. In this manuscript, we describe experimental and theoretical approaches for using modular Elastic Elements (EE) to efficiently achieve multi-axis, high-performance F/M sensors.

A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors.

Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T-cell activity against solid tumors.

Mineralocorticoid Receptor Deficiency in Macrophages Inhibits Neointimal Hyperplasia and Suppresses Macrophage Inflammation Through SGK1-AP1/NF-κB Pathways.

Objective: Restenosis after percutaneous coronary intervention remains to be a serious medical problem. Although mineralocorticoid receptor (MR) has been implicated as a potential target for treating restenosis, the cellular and molecular mechanisms are largely unknown. This study aims to explore the functions of macrophage MR in neointimal hyperplasia and to delineate the molecular mechanisms.

A propensity score matching analysis of survival following segmentectomy or wedge resection in early-stage lung invasive adenocarcinoma or squamous cell carcinoma.

Purpose: To compare the survival outcomes following segmentectomy or wedge resection in early-stage lung cancer.

Methods: A total of 5880 patients with invasive lung adenocarcinoma or squamous cell carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study, of which 1156 received segmentectomy. Baseline characteristics were balanced using propensity score methods.

Endothelial p110γPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury.

Background: The integrity of endothelial monolayer is a sine qua non for vascular homeostasis and maintenance of tissue-fluid balance. However, little is known about the signaling pathways regulating regeneration of the endothelial barrier after inflammatory vascular injury.

Methods And Results: Using genetic and pharmacological approaches, we demonstrated that endothelial regeneration selectively requires activation of p110γPI3K signaling, which thereby mediates the expression of the endothelial reparative transcription factor Forkhead box M1 (FoxM1).

MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue.

Rationale: The pathogenesis of insulin resistance involves dysregulated gene expression and function in multiple cell types, including endothelial cells (ECs). Post-transcriptional mechanisms such as microRNA-mediated regulation of gene expression could affect insulin action by modulating EC function.

Objective: To determine whether microRNA-181b (miR-181b) affects the pathogenesis of insulin resistance by regulating EC function in white adipose tissue during obesity.

OsBRI1 Activates BR Signaling by Preventing Binding between the TPR and Kinase Domains of OsBSK3 via Phosphorylation.

Many plant receptor kinases transduce signals through receptor-like cytoplasmic kinases (RLCKs); however, the molecular mechanisms that create an effective on-off switch are unknown. The receptor kinase BR INSENSITIVE1 (BRI1) transduces brassinosteroid (BR) signal by phosphorylating members of the BR-signaling kinase (BSK) family of RLCKs, which contain a kinase domain and a C-terminal tetratricopeptide repeat (TPR) domain. Here, we show that the BR signaling function of BSKs is conserved in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) and that the TPR domain of BSKs functions as a "phospho-switchable" autoregulatory domain to control BSKs' activity.

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.

[Application of LIBS in Element Analysis of Nanometer Thin Film Prepared on Silicon Basement].

In order to develop a method to analyze the metal elements in the thin film samples rapidly, directly and without sample preparation, a laboratory LIBS system was established recently for nanometer film analysis. This system could determine the position of sample plane, observe the profiles of sample after pulse-material interaction and detect the plasma morphologyand spectral emission at the same time. Samplesused were ZrO2 films about 40 nm thickness prepared on Si by a sol-gel process, and they were located on a manual X-Y-Z translational stage with theaccuracy of 0.

Ajuba Preferentially Binds LXRα/RXRγ Heterodimer to Enhance LXR Target Gene Expression in Liver Cells.

The liver X receptors (LXRs) are important regulators of lipid, cholesterol, and glucose homeostasis by transcriptional regulation of many key genes in these processes, and the transcriptional activities of LXRs are finely controlled by cooperating with retinoid X receptors and many other coregulators. Here, we report that the LIM protein Ajuba binds to the hinge and the ligand binding domains of LXRα via its C-terminal tandem LIM motifs and enhances LXR target gene expression in liver cells. Depletion of Ajuba in HepG2 cells and in mouse primary hepatocytes decreases LXR target gene expression, whereas stable expression of Ajuba in HepG2 cells results in increased expression of these genes.

Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic Ischemia: Potential Impact on the Development of Coronary Collateral Circulation.

Objective: Revascularization is an essential process to compensate for cardiac underperfusion and, therefore, preserves cardiac function in the face of chronic ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase 2 (ALDH2) in cardiac protection after ischemia. This study was designed to determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to explore the underlying mechanism involved.