YAP-galectin-3 signaling mediates endothelial dysfunction in angiotensin II-induced hypertension in mice.

BACKGROUND: Vascular endothelial dysfunction is regarded as an early event of hypertension. Galectin-3 (Gal-3) is known to participate in various pathological processes. Whilst previous studies showed that inhibition of Gal-3 effectively ameliorates angiotensin II (Ang II)-induced atherosclerosis or hypertension, it remains unclear whether Ang II regulates Gal-3 expression and actions in vascular endothelium. METHODS: Using techniques of molecular biology and myograph, we investigated Ang II-mediated changes in Gal-3 expression and activity in thoracic aortas and mesenteric arteries from wild-type and Gal-3 gene deleted (Gal-3-/-) mice and cultured endothelial cells. RESULTS: The serum level of Gal-3 was significantly higher in hypertensive patients or in mice with chronic Ang II-infusion. Ang II infusion to wild-type mice enhanced Gal-3 expression in the aortic and mesenteric arteries, elevated systolic blood pressure and impaired endothelium-dependent relaxation of the thoracic aortas and mesenteric arteries, changes that were abolished in Gal-3-/- mice. In human umbilical vein endothelial cells, Ang II significantly upregulated Gal-3 expression by promoting nuclear localization of Yes-associated protein (YAP) and its interaction with transcription factor Tead1 with enhanced YAP/Tead1 binding to Gal-3 gene promoter region. Furthermore, Gal-3 deletion augmented the bioavailability of nitric oxide, suppressed oxidative stress, and alleviated inflammation in the thoracic aorta of Ang II-infused mice or endothelial cells exposed to Ang II. CONCLUSIONS: Our results demonstrate for the first time that Ang II upregulates Gal-3 expression via increment in YAP nuclear localization in vascular endothelium, and that Gal-3 mediates endothelial dysfunction contributing to the development of hypertension.

Research on the Shock Wave Overpressure Peak Measurement Method Based on Equilateral Ternary Array.

The measurement process of ground shock wave overpressure is influenced by complex field conditions, leading to notable errors in peak measurements. This study introduces a novel pressure measurement model that utilizes the Rankine-Hugoniot relation and an equilateral ternary array. The research delves into examining the influence of three key parameters (array size, shock wave incidence angle, and velocity) on the precision of pressure measurement through detailed simulations. The accuracy is compared with that of a dual-sensor array under the same conditions. Static explosion tests were conducted using bare charges of 0.3 kg and 3 kg TNT to verify the numerical simulation results. The findings indicate that the equilateral ternary array shock wave pressure measurement method demonstrates a strong anti-interference capability. It effectively reduces the peak overpressure error measured directly by the shock wave pressure sensor from 17.73% to 1.25% in the test environment. Furthermore, this method allows for velocity-based measurement of shock wave overpressure peaks in all propagation direction, with a maximum measurement error of 3.59% for shock wave overpressure peaks ≤ 9.08 MPa.

E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/ß-Catenin pathway in ovarian cancer.

Ovarian cancer is one of the leading causes of death in female reproductive system cancers. However, the pathogenesis of ovarian cancer remains elusive. Our aim is to investigate the potential targets for ovarian cancer. Two microarray datasets were obtained from the Gene Expression Omnibus public database. Using R package limma, the differentially expressed genes (DEGs) were identified from the datasets. There were 95 overlapping DEGs in two microarray datasets. GO, KEGG pathway analysis, and protein-protein interaction (PPI) network analysis were carried out based on the DEGs. Wnt signaling pathway and cell cycle were enriched in the KEGG pathway analysis. Moreover, the top 10 hub genes with the most nodes were determined by PPI network analysis. E2F8, one of hub genes was positively linked to a bad outcome in ovarian cancer patients. Furthermore, E2F8 knockdown suppressed cell proliferation and induced cell cycle arrest in ovarian cancer. In addition, we found that silencing E2F8 inhibited the Wnt/ß-catenin signaling pathway. In ovarian cancer cells with E2F8 knockdown, overexpressing ß-catenin restored both the suppressed capacity of cell proliferation and cell cycle progression. Therefore, our results revealed that E2F8 had an involvement in the development of ovarian cancer which might act as a therapeutic target.

High-Gain Omnidirectional Dual-Polarized Antenna for Sink Nodes in Wireless Sensor Networks.

In wireless sensor networks (WSN), a sink node receives signals from a large number of sensor nodes. Hence, the sink nodes are required to integrate compact antennas with high performances, such as high gain, dual polarizations, and omnidirectional radiation. In this paper, a high-gain omnidirectional dual-polarized (HGODP) antenna with a slot-cavity structure is proposed for WSN. The proposed antenna integrates dual omnidirectional antennas with orthogonal polarizations, i.e., a thin open-ended cavity for horizontal polarization and four folded slots for vertical polarization. Due to the orthogonal operating modes of the dual polarizations, the antenna configuration is constructed within a compact volume, but with an independent design. A prototype of the proposed antenna is fabricated and measured within a ruler-like profile. The experimental results show that the realized gains are higher than 6.5 dBi and are achieved for both dual polarizations in 2.37~2.54 GHz. With the merits of high gain, high isolation, and omnidirectional radiation, the proposed compact antenna exhibits promising usage for sink nodes in WSN.

Distinct non-coding RNAs confer root-dependent sense transgene-induced post-transcriptional gene silencing and nitrogen-dependent post-transcriptional regulation to AtAMT1;1 transcripts in Arabidopsis roots.

High-affinity ammonium uptake in roots mediate by AMT1-type ammonium transporters, which are tightly controlled at multiple regulatory levels for adapting various nitrogen availability. For Arabidopsis AtAMT1;1 gene, in addition to the transcriptional and post-translational controls, an organ-dependent and N-dependent post-transcriptional regulation was suggested as an additional regulatory step for fine tuning ammonium uptake, but the underlying mechanisms remain to be elucidated. Here, we showed that degradation of AtAMT1;1 transcript in roots of Pro35s:AtAMT1;1-transformed atamt1;1-1 Arabidopsis plants resulted from RDR6-dependent sense transgene-induced post-transcriptional gene silencing (S-PTGS). The siRNAs for S-PTGS may derive from the aberrant RNA, of which the production was co-determined by sequence feature and excessive expression of AtAMT1;1. Switching to the expression of AtAMT1;1 driven by ProAtUBQ10 or of AtAMT1;1 mutated at two siRNA-targeted hotspots reduced AtAMT1;1-specific siRNAs and overcame S-PTGS in roots. In roots of these lines, however, the steady-state transcript levels of AtAMT1;1 still significantly decreased under conditions of N-sufficiency compared with N-deficiency, confirming a N-dependent post-transcriptional regulatory manner. A crucial role of the 207-bp 3'-end sequence of AtAMT1;1 was further demonstrated by N-dependent accumulation of chimeric-AtAMT1;1 transcript in T-DNA insertion lines and of GFP-tagged chimeric-AtAMT1;1 transcript in transgenic lines. A novel non-coding RNA (ncRNA), which was highly abundant in N-sufficient roots, may target the above-identified 3'-end region for the degrading AtAMT1;1 transcript. This degradation could be prevented by a mutation on the AtAMT1;1 transcript at a potential cleavage site (+1458). These results suggested two distinct mechanisms of regulating AtAMT1;1 mRNA turnover by ncRNA for strictly control of ammonium uptake in roots.

circSNX6 (hsa_circ_0031608) enhances drug resistance of non-small cell lung cancer (NSCLC) via miR-137.

circRNAs have been suggested to modulate NSCLC tumorigenesis and drug resistance. Whether circSNX6 affects NSCLC remains unclear. In this study, we aim to investigate the role of circSNX6 in drug resistance of NSCLC exposed to cisplatin. RT-qPCR method was used to investigate expression levels of circSNX6, miR-137 and CXCL12. MTT, cell colony formation and TUNEL assays were utilized to assess cell viability, proliferation, apoptosis, respectively. Xenograft assay was conducted to examinein vivotumor growth. circSNX6 overexpression caused enhanced cell viability and proliferation of H1299 and Calu-1, while it inhibited apoptosis under cisplatin treatment. miR-137 inhibitor greatly rescued cell viability, proliferation and apoptosis of circSNX6 knockdown H1299 cells. miR-137 mimic increased ROS generation, as well as reduced GSH and SOD levels, whereas miR-137 inhibitor exerted opposing effect. circSNX6 knockdown also enhanced ROS generation, as well as decreased GSH and SOD levels. CXCL12 partially restored miR-137 mimic-modulated cell viability, proliferation and apoptosis. Herein, our group proposes circSNX6 as key regulator for drug resistance of NSCLC. The findings provide solid groundings for understanding of NSCLC pathogenesis and development of therapeutics.

Pharmacological corrections of the mutant hERG channels by posaconazole.

Properties of mutant human ether-à-go-go-related gene (hERG) channels can be modified by some antibiotics. However, the pharmacological effects of posaconazole on cardiomyocyte hERG channels remain unclear. Whole-cell patch clamping, western blotting and laser confocal scanning microscopy were used to evaluate the effects of posaconazole on wild-type (WT)-, A561V- and L539 fs/47-hERG channels expressed in human embryonic kidney (HEK) 293 cells. In electrophysiological experiments, HEK 293 cells were transiently co-transfected with equal amounts of WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG plasmids to mimic a heterozygous genotype. Posaconazole (30 µM) increased tail currents in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG by 82.65%, 147.72% and 134.73%, respectively, compared to controls. Posaconazole increased hERG protein expression in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG compared to controls condition as well as their trafficking to the cell membrane. To our knowledge, this is the first study to show that antifungal agent posaconazole rescues the mutant A561 V-hERG and L539 fs/47-hERG channels by altering the gating kinetics, enhancing the expression and trafficking of hERG channels. The results demonstrate that posaconazole could be a promising candidate for the prevention and treatment of long QT syndrome and other arrhythmia-related diseases.

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis.

Ovarian cancer is the most lethal gynaecological cancer, and resistance of platinum-based chemotherapy is the main reason for treatment failure. The aim of the present study was to identify candidate genes involved in ovarian cancer platinum response by analysing genes from homologous recombination and Fanconi anaemia pathways. Associations between these two functional genes were explored in the study, and we performed a random walk algorithm based on reconstructed gene-gene network, including protein-protein interaction and co-expression relations. Following the random walk, all genes were ranked and GSEA analysis showed that the biological functions focused primarily on autophagy, histone modification and gluconeogenesis. Based on three types of seed nodes, the top two genes were utilized as examples. We selected a total of six candidate genes (FANCA, FANCG, POLD1, KDM1A, BLM and BRCA1) for subsequent verification. The validation results of the six candidate genes have significance in three independent ovarian cancer data sets with platinum-resistant and platinum-sensitive information. To explore the correlation between biomarkers and clinical prognostic factors, we performed differential analysis and multivariate clinical subgroup analysis for six candidate genes at both mRNA and protein levels. And each of the six candidate genes and their neighbouring genes with a mutation rate greater than 10% were also analysed by network construction and functional enrichment analysis. In the meanwhile, the survival analysis for platinum-treated patients was performed in the current study. Finally, the RT-qPCR assay was used to determine the performance of candidate genes in ovarian cancer platinum response. Taken together, this research demonstrated that comprehensive bioinformatics methods could help to understand the molecular mechanism of platinum response and provide new strategies for overcoming platinum resistance in ovarian cancer treatment.

Interfacial viscoelasticity and jamming of colloidal particles at fluid-fluid interfaces: a review.

Colloidal particles can be adsorbed at fluid-fluid interfaces, a phenomenon frequently observed in particle-stabilized foams, Pickering emulsions, and bijels. Particles adsorbed at interfaces exhibit unique physical and chemical behaviors, which affect the mechanical properties of the interface. Therefore, interfacial colloidal particles are of interest in terms of both fundamental and applied research. In this paper, we review studies on the adsorption of colloidal particles at fluid-fluid interfaces, from both thermodynamic and mechanical points of view, and discuss the differences as compared with surfactants and polymers. The unique particle interactions induced by the interfaces as well as the particle dynamics including lateral diffusion and contact line relaxation will be presented. We focus on the rearrangement of the particles and the resultant interfacial viscoelasticity. Particular emphasis will be given to the effects of particle shape, size, and surface hydrophobicity on the interfacial particle assembly and the mechanical properties of the obtained particle layer. We will also summarize recent advances in interfacial jamming behavior caused by adsorption of particles at interfaces. The buckling and cracking behavior of particle layers will be discussed from a mechanical perspective. Finally, we suggest several potential directions for future research in this area.

Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma.

BACKGROUND: Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na+/K+-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC. METHODS: Gene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype-Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia. RESULTS: The expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3-5%. CONCLUSIONS: These results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2.

The carnitine shuttle system (CSS) plays a crucial role in the transportation of fatty acyls during fatty acid ß-oxidation for energy supplementation, especially in cases of high energy demand, such as in cancer. In this study, to systematically characterize alterations of the CSS in hepatocellular carcinoma (HCC), acylcarnitine metabolic profiling was carried out on 80 pairs of HCC tissues and adjacent noncancerous tissues (ANTs) by using ultra-performance liquid chromatography coupled to mass spectrometry. Twenty-four acylcarnitines classified into five categories were identified and characterized between HCCs and ANTs. Notably, increased saturated long-chain acylcarnitines (LCACs) and decreased short- and medium-chain acylcarnitines (S/MCACs) were simultaneously observed in HCC samples. Subsequent correlation network and heatmap analysis indicated low correlations between LCACs and S/MCACs. The mRNA and protein expressions of carnitine palmitoyltransferase 2 (CPT2) was significantly downregulated in HCC samples, whereas CPT1A expression was not significantly changed. Correspondingly, the relative levels of S/MCACs were reduced and those of LCACs were increased in BEL-7402/CPT2-knockdown cells compared to negative controls. Both results suggested that decreased shuttling efficiency in HCC might be associated with downregulation of CPT2. In addition, decreases in the mRNA expression of acetyl-CoA acyltransferase 2 were also observed in HCC tissues and BEL-7402/CPT2-knockdown cells, suggesting potential low ß-oxidation efficiency, which was consistent with the increased expression of stearoyl-CoA desaturase 1 in both samples. The systematic strategy applied in our study illustrated decreased shuttling efficiency of the carnitine shuttle system in HCC and can provide biologists with an in-depth understanding of ß-oxidation in HCC.

Ammonium and nitrate regulate NH4+ uptake activity of Arabidopsis ammonium transporter AtAMT1;3 via phosphorylation at multiple C-terminal sites.

In plants, nutrient transporters require tight regulation to ensure optimal uptake in complex environments. The activities of many nutrient transporters are post-translationally regulated by reversible phosphorylation, allowing rapid adaptation to variable environmental conditions. Here, we show that the Arabidopsis root epidermis-expressed ammonium transporter AtAMT1;3 was dynamically (de-)phosphorylated at multiple sites in the cytosolic C-terminal region (CTR) responding to ammonium and nitrate signals. Under ammonium resupply rapid phosphorylation of a Thr residue (T464) in the conserved part of the CTR (CTRC) effectively inhibited AtAMT1;3-dependent NH4+ uptake. Moreover, phosphorylation of Thr (T494), one of three phosphorylation sites in the non-conserved part of the CTR (CRTNC), moderately decreased the NH4+ transport activity of AtAMT1;3, as deduced from functional analysis of phospho-mimic mutants in yeast, oocytes, and transgenic Arabidopsis. Double phospho-mutants indicated a role of T494 in fine-tuning the NH4+ transport activity when T464 was non-phosphorylated. Transient dephosphorylation of T494 with nitrate resupply closely paralleled a transient increase in ammonium uptake. These results suggest that T464 phosphorylation at the CTRC acts as a prime switch to prevent excess ammonium influx, while T494 phosphorylation at the CTRNC fine tunes ammonium uptake in response to nitrate. This provides a sophisticated regulatory mechanism for plant ammonium transporters to achieve optimal ammonium uptake in response to various nitrogen forms.

Branching of interfacial cracks of carbon nanotube layers at the air-water interface⋆.

We study the surfactant-induced fracture of carbon nanotube layers at the air-water interface. The interfacial cracks exhibit branched morphologies. The propagation velocity V of the cracks follows a power law as [Formula: see text] , which is independent of the surface coverage of the layers as well as the surfactant concentration. However, the crack morphology changes from lightning-like to flower-like with the increasing of SDS concentration. A higher surfactant concentration does not accelerate the crack propagation velocity, whereas it significantly enhances the crack areas due to the stronger interfacial compression effect. Our results may shed light on the understanding of branching dynamics of interfacial cracks for 2-dimensional viscoelastic systems.

The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway.

Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6 g/L) and experimental group 2 (12 g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.

Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR-362-5p/Nf-κB axis.

The long non-coding RNA segment cancer susceptibility candidate 2 (CASC2) has been shown to suppress tumor growth in a variety of cancers, including hepatocellular carcinoma (HCC). However, the mechanism by which CASC2 exerts control over HCC has yet to be established. In the present study, we first demonstrated that CASC2 is downregulated in human HCC tissues and HCC cell lines as compared to adjacent non-tumor tissues (NTTs) and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, we identified the microRNA miR-362-5p as an endogenous target of CASC2. Through the use of wild type and mutant CASC2 binding sites inserted into psiCHECK-2 luciferase reporter plasmids, as well as qRT-PCR, we determined that CASC2 overexpression reduces miR-362-5p expression levels, while inhibiting CASC2 activity increases miR-362-5p expression. Past research has shown that miR-362-5p stimulates the NF-κB pathway, which has been implicated in the survival and proliferation of a variety of cancer cells. We therefore investigated the effects of CASC2 expression on NF-κB pathway activity. Ultimately, we determined that CASC2 regulates HCC cell activity by targeting miR-362-5p and thus inhibiting the NF-κB pathway. The present study not only identifies CASC2 as an important HCC cell regulator, but also suggests its mechanism of action. It therefore provides the basis for designing strategies to target CASC2 activity and thereby inhibit HCC growth and progression.

Nonlinear mechanical behaviors of a nanoparticle monolayer at the air-water interface.

Nanoparticle can adsorb at the air-water interface and gives rise to the special interfacial mechanical properties. With the influence of external stimulus, the adsorption state of the particles may be changed and in turn the mechanical properties of the particle layer. In this work, we study the mechanical properties of a monolayer of silica nanoparticles deposited in the Langmuir trough. The area of the monolayer was varied sinusoidally by two oscillating barriers and the surface pressure was monitored by two orthogonal Wilhelmy plates. It has been found that the surface pressure of the particle layer exhibits a significant anisotropic effect. At the early stage of the oscillation, the surface pressure versus time is sinusoidal. However, with the increase of the oscillation time, the response of the particle layer significantly deviates the sinusoidal function, which implies that the response becomes nonlinear caused by a long-term oscillation. The fast Fourier Transformation (FFT) of the surface pressure data shows that the non-sinusoidal response is composed of several fundamental frequency responses. We eventually obtained the time variation of the compression modulus E and shear modulus G . A possible mechanism was proposed to account for the mechanical properties change and the nonlinear behavior of the particle monolayer.

Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles.

The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na+ channels, and modulate their function. Mutations that affect iFGF/FHF-Na+ channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca2+ channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation. Patch clamp recordings from ventricular myocytes isolated from Fgf13 knockout mice showed a ~25% reduction in peak Na+ channel current density and a hyperpolarizing shift in steady-state inactivation. Electrocardiograms on Fgf13 knockout mice showed a prolonged QRS duration. The Na+ channel blocker flecainide further prolonged QRS duration and triggered ventricular tachyarrhythmias only in Fgf13 knockout mice, suggesting that arrhythmia vulnerability resulted, at least in part, from a loss of functioning Na+ channels. Consistent with these effects on Na+ channels, action potentials in Fgf13 knockout mice, compared to Cre control mice, exhibited slower upstrokes and reduced amplitude, but unexpectedly had longer durations. We investigated candidate sources of the prolonged action potential durations in myocytes from Fgf13 knockout mice and found a reduction of the transient outward K+ current (Ito). Fgf13 knockout did not alter whole-cell protein levels of Kv4.2 and Kv4.3, the Ito pore-forming subunits, but did decrease Kv4.2 and Kv4.3 at the sarcolemma. No changes were seen in the sustained outward K+ current or voltage-gated Ca2+ current, other candidate contributors to the increased action potential duration. These results implicate that FGF13 is a critical cardiac Na+ channel modulator and Fgf13 knockout mice have increased arrhythmia susceptibility in the setting of Na+ channel blockade. The unanticipated effect on Ito revealed new FGF13 properties and the unexpected lack of an effect on voltage-gated Ca2+ channels highlight potential compensatory changes in vivo not readily revealed with acute Fgf13 knockdown in cultured cardiomyocytes.

Novel asymmetric cryptosystem based on distorted wavefront beam illumination and double-random phase encoding.

Herein, we propose a new security enhancing method that employs wavefront aberrations as optical keys to improve the resistance capabilities of conventional double-random phase encoding (DRPE) optical cryptosystems. This study has two main innovations. First, we exploit a special beam-expander afocal-reflecting to produce different types of aberrations, and the wavefront distortion can be altered by changing the shape of the afocal-reflecting system using a deformable mirror. Then, we reconstruct the wavefront aberrations via the surface fitting of Zernike polynomials and use the reconstructed aberrations as novel asymmetric vector keys. The ideal wavefront and the distorted wavefront obtained by wavefront sensing can be regarded as a pair of private and public keys. The wavelength and focal length of the Fourier lens can be used as additional keys to increase the number of degrees of freedom. This novel cryptosystem can enhance the resistance to various attacks aimed at DRPE systems. Finally, we conduct ZEMAX and MATLAB simulations to demonstrate the superiority of this method.

A Novel MEMS Gyro North Finder Design Based on the Rotation Modulation Technique.

Gyro north finders have been widely used in maneuvering weapon orientation, oil drilling and other areas. This paper proposes a novel Micro-Electro-Mechanical System (MEMS) gyroscope north finder based on the rotation modulation (RM) technique. Two rotation modulation modes (static and dynamic modulation) are applied. Compared to the traditional gyro north finders, only one single MEMS gyroscope and one MEMS accelerometer are needed, reducing the total cost since high-precision gyroscopes and accelerometers are the most expensive components in gyro north finders. To reduce the volume and enhance the reliability, wireless power and wireless data transmission technique are introduced into the rotation modulation system for the first time. To enhance the system robustness, the robust least square method (RLSM) and robust Kalman filter (RKF) are applied in the static and dynamic north finding methods, respectively. Experimental characterization resulted in a static accuracy of 0.66° and a dynamic repeatability accuracy of 1°, respectively, confirming the excellent potential of the novel north finding system. The proposed single gyro and single accelerometer north finding scheme is universal, and can be an important reference to both scientific research and industrial applications.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)] benzoylurea induces cell-cycle arrest and apoptosis in human cancer cells.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)]benzoylurea (SUD) is a novel synthesized benzoylurea derivative. We selected several human cancer cell lines to investigate whether SUD can inhibit the growth of cancer cells. We selected the liver cell line L-02 to investigate the effect of SUD on the normal cells. Flow cytometric analysis was used to detect the effect of SUD on cell cycle, Hoechst 33258 staining was used to evaluate the apoptosis induced by SUD, real-time fluorescence quantitative PCR was used to investigate the expression of the cell cycle-relevant and apoptosis-relevant genes, a reactive oxygen species (ROS) assay was used to observe the production of ROS, and western blotting was used to determine the level of cell cycle-relevant and apoptosis-relevant proteins. According to the results of the MTT assay, the growth of human cancer cell lines was significantly inhibited by SUD treatment in a time-dependent and concentration-dependent manner; however, the growth of human normal cells was not significantly inhibited by SUD treatment. The results of flow cytometric analyses showed that SUD induced cell-cycle arrest at the G2-phase in MCF-7 cells and at the G1-phase in BGC-823 cells. The results of Hoechst 33258 staining showed that SUD induced apoptosis in MCF-7 and BGC-823 cells. The results of the ROS assay showed that the production of ROS was increased by SUD in MCF-7 and BGC-823 cells. Our research suggests that the growth-inhibitory effect of SUD on MCF-7 cells was related to G2-phase arrest, which was associated with the upregulated expression of p53 and Chk1 proteins, and downregulation of the cyclin B1 gene, cdc25a, and cyclin-dependent kinase 1 (CDK1) proteins; the growth-inhibitory effect of SUD on BGC-823 cells was related to G1-phase arrest, which was associated with upregulation of the p53 gene and Chk1 protein and downregulation of cdc25a protein and the CDK4 gene. SUD also induced apoptosis in MCF-7 and BGC-823 cell lines through the mitochondrial pathway in a p53-dependent manner.