Evolocumab prevents atrial fibrillation in rheumatoid arthritis rats through restraint of PCSK9 induced atrial remodeling.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear. OBJECTIVES: To explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism. METHODS: We established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund's incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF. RESULTS: AF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF. CONCLUSION: This study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.

Cerebrospinal fluid electrolytes and acid-base in diabetic patients.

BACKGROUND: Diabetes mellitus (DM) has detrimental effects on the function of microvascular beds, resulting in blood-brain barrier (BBB) dysfunction. The objective of the study was to investigate whether DM affects the brain physiology through composition of cerebrospinal fluid (CSF) and compare gas tension and electrolyte levels in CSF between the diabetic and nondiabetic populations. METHODS: Patients aged between 20 and 70 years scheduled for elective orthopedic or urologic surgery requiring spinal anesthesia were enrolled. They were assigned to either of the two groups (control or type 2 DM). Gas tension and electrolytes in the CSF and whole blood samples were measured in both groups. RESULTS: All 49 enrolled patients (24 in the control and 25 in the DM group) completed the study. The concentrations of Na+ and Mg2+ in the blood were significantly lower in the DM group than those in the control. The levels of pCO2 and HCO 3 - in the CSF were lower in the DM group than in the control group. In addition, there was a marked increase in the glucose level in both the blood and CSF in the DM group. CONCLUSION: The results show that there were some homeostatic changes in blood and CSF in patients with DM.

Complete replacement of metal in metal oxide nanowires via atomic diffusion: In/ZnO case study.

Atomic diffusion is a fundamental process that dictates material science and engineering. Direct visualization of atomic diffusion process in ultrahigh vacuum in situ TEM could comprehend the fundamental information about metal-semiconductor interface dynamics, phase transitions, and different nanostructure growth phenomenon. Here, we demonstrate the in situ TEM observations of the complete replacement of ZnO nanowire by indium with different growth directions. In situ TEM analyses reveal that the diffusion processes strongly depend and are dominated by the interface dynamics between indium and ZnO. The diffusion exhibited a distinct ledge migration by surface diffusion at [001]-ZnO while continuous migration with slight/no ledges by inner diffusion at [100]-ZnO. The process is explained based on thermodynamic evaluation and growth kinetics. The results present the potential possibilities to completely replace metal-oxide semiconductors with metal nanowires without oxidation and form crystalline metal nanowires with precise epitaxial metal-semiconductor atomic interface. Formation of such single crystalline metal nanowire without oxidation by diffusion to the metal oxide is unique and is crucial in nanodevice performances, which is rather challenging from a manufacturing perspective of 1D nanodevices.

Harmonic-resonator-based triboelectric nanogenerator as a sustainable power source and a self-powered active vibration sensor.

A harmonic-resonator-based triboelectric nanogenerator (TENG) is presented as a sustainable power source and an active vibration sensor. It can effectively respond to vibration frequencies ranging from 2 to 200 Hz with a considerably wide working bandwidth of 13.4 Hz. This work not only presents a new principle in the field of vibration energy harvesting but also greatly expands the applicability of TENGs.

Single-step formation of ZnO/ZnWO(x) bilayer structure via interfacial engineering for high performance and low energy consumption resistive memory with controllable high resistance states.

A spontaneously formed ZnO/ZnWOx bilayer resistive memory via an interfacial engineering by one-step sputtering process with controllable high resistance states was demonstrated. The detailed formation mechanism and microstructure of the ZnWOx layer was explored by X-ray photoemission spectroscopy (XPS) and transmission electron microscope in detail. The reduced trapping depths from 0.46 to 0.29 eV were found after formation of ZnWOx layer, resulting in an asymmetric I-V behavior. In particular, the reduction of compliance current significantly reduces the switching current to reach the stable operation of device, enabling less energy consumption. Furthermore, we demonstrated an excellent performance of the complementary resistive switching (CRS) based on the ZnO/ZnWOx bilayer structure with DC endurance >200 cycles for a possible application in three-dimensional multilayer stacking.

Self-powered magnetic sensor based on a triboelectric nanogenerator.

Magnetic sensors are usually based on the Hall effect or a magnetoresistive sensing mechanism. Here we demonstrate that a nanogenerator can serve as a sensor for detecting the variation of the time-dependent magnetic field. The output voltage of the sensor was found to exponentially increase with increasing magnetic field. The detection sensitivities for the change and the changing rate of magnetic field are about 0.0363 ± 0.0004 ln(mV)/G and 0.0497 ± 0.0006 ln(mV)/(G/s), respectively. The response time and reset time of the sensor are about 0.13 and 0.34 s, respectively. The fabricated sensor has a detection resolution of about 3 G and can work under low frequencies (<0.4 Hz).

Free-standing and single-crystalline Fe(1-x)Mn(x)Si nanowires with room-temperature ferromagnetism and excellent magnetic response.

High-aspect-ratio Fe(1-x)Mn(x)Si nanowires with room-temperature ferromagnetism were synthesized by a chemical vapor deposition (CVD) method in one step. This is the first report of ternary silicide nanowires using magnetic Mn ions to partially replace metal sites in the host matrix. Here we report the excellent magnetic characteristics of Fe(1-x)Mn(x)Si nanowires, which exhibit strong ferromagnetism at room temperature and high magnetoresistance (MR) variation. As-synthesized Fe(1-x)Mn(x)Si nanowires show a hyperbranched morphology and a spin-disorder behavior. The strong spin interaction in Fe(1-x)Mn(x)Si nanowires, induced by the substitution of Fe sublattices for magnetic Mn ions, was revealed in the hysteresis loops. The magnetization versus magnetic field (M-H) curves of Fe(1-x)Mn(x)Si nanowires are much less sensitive to the temperature variation from 10 to 300 K than those of FeSi nanowires. Remarkably, the excellent MR performance, -41.6% at 25 K with a magnetic field of 9 T, was demonstrated in an individual Fe(0.88)Mn(0.12)Si nanowire.

One-dimensional germanium nanostructures--formation and their electron field emission properties.

Ge nanostructures were synthesized by reduction of GeO(2) in H(2) atmosphere at various temperatures. Entangled and straight Ge nanowires with oxide shells were grown at high temperatures. Ge nanowires with various numbers of nodules were obtained at low temperatures. Ge nanowires without nodules exhibited remarkable field emission properties with a turn-on field of 4.6 V µm(-1) and field enhancement factor of 1242.