Endothelial Drp1 Couples VEGF-induced Redox Signaling with Glycolysis Through Cysteine Oxidation to Drive Angiogenesis.

Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H 2 O 2 signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys 644 , promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys 299 / 304 via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. In vivo , mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered "redox-dead" (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.

Evaluation of THz wave transmission performance in TOPAS-based heptagonal photonic crystal fiber (He-PCF).

PCF denotes photonic crystal fiber which is utilized for terahertz (THz) waveguides and cladding in the shape of a hexagon with two elliptical air apertures (AHs), which are discussed. Such differentiation is made: When the frequency is 1 THz, effective material loss (EML) to a minimum of 0.028 cm-1 has been achieved. Making use of the heptagonal photonic crystal fiber (He-PCF) architecture, every simulation result utilizing COMSOL Multiphysics software implements the perfectly match layer (PML) and finite element method (FEM) boundary conditions. The He-PCF fiber demonstrates an effective mode loss (EML) of 0.028 cm-1 that is negligible, a substantial effective area (EA) measuring 7.31 × 10-8 m2 and an 80 % power concentration encompassing the central area at 1 THz frequency. Furthermore, regarding crucial optical guiding aspects like confinement loss, dispersion, and modality, a small study with respect to power fraction along with effective mode area (EMA) has again been conducted. Here, He-PCF THz waveguide is anticipated to provide a notable improvement in the current design for the communication field. Moreover, our suggested the PCF demonstrates perception by a solitary mode, as indicated through the utilization of the V-parameter, across a range in frequency spanning among 0.80 and 3 THz. Thus, it is anticipated that the layout of He-PCF fibers will facilitate efficient transmission of terahertz (THz) signals in a variety of communication applications.

Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro.

Oxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from Bacillus siamensis. SH21 exhibited very powerful antioxidant and reactive oxygen species (ROS) generation inhibition activity in a dose-dependent approach. The mRNA and protein levels of antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx-1) were enhanced in the SH21-treated sample. SH21 also increased the transcriptional and translational activities of NF-E2-related factor 2 (Nrf2) with the subsequent development of detoxifying enzyme heme oxygenase-1 (HO-1). In addition, SH21 showed potential anti-inflammatory activity via inhibition of nitric oxide (NO) and proinflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At concentrations of 60, 80, and 100 µg/mL, SH21 potentially suppressed nitric oxide synthase (iNOS) and cytokine gene expressions. Furthermore, SH21 significantly released lactate dehydrogenase (LDH) enzyme in cancer cell supernatant in a concentration-dependent manner and showed strong activity against three tested cancer cell lines, including HL-60, A549, and Hela. Our results suggest that SH21 has effective antioxidant, anti-inflammatory, and anticancer effects and could be an excellent therapeutic agent against inflammation-related diseases.

Involvement of calcium ions in amyloid-ß-induced lamin fragmentation.

Amyloid-ß (Aß) peptide, the main pathogenic peptide in Alzheimer's disease, has been shown to induce an increase in cytoplasmic calcium concentration (CCC). In the current study, we explored the cytotoxic signal transduction pathway in 42-amino-acid Aß (Aß42)-treated HeLa cells in relation to the increase in CCC. The increase in CCC was prominent in cells treated twice with oligomeric Aß42. We previously showed that double treatment also promoted Aß-induced lamin fragmentation (AILF), which appears to be mediated by cathepsin L. Apoptotic caspase activation was a downstream event of AILF. The Ca2+ chelator BAPTA-AM suppressed cell death, cathepsin L activation, AILF, and caspase activation in Aß-treated cells. These results indicate that Aß42 induces an increase in CCC, which is an event upstream of the cytotoxic processes. The products of AILF are different from those produced by other cell death-inducing agents, such as staurosporine, which induces caspase-6-mediated lamin fragmentation (CMLF). CMLF was unaffected by BAPTA-AM and was not detected in cells treated with Aß42, indicating that Aß42 peptide induced a specific cytotoxic pathway involving AILF via increased CCC. We confirmed that the same processes (except caspase activation) operated in Aß42-treated neuroblastoma SH-SY5Y cells.

Evidence for a Strong Relationship between the Cytotoxicity and Intracellular Location of ß-Amyloid.

ß-Amyloid (Aß) is a hallmark peptide of Alzheimer's disease (AD). Herein, we explored the mechanism underlying the cytotoxicity of this peptide. Double treatment with oligomeric 42-amino-acid Aß (Aß42) species, which are more cytotoxic than other conformers such as monomers and fibrils, resulted in increased cytotoxicity. Under this treatment condition, an increase in intracellular localization of the peptide was observed, which indicated that the peptide administered extracellularly entered the cells. The cell-permeable peptide TAT-tagged Aß42 (tAß42), which was newly prepared for the study and found to be highly cell-permeable and soluble, induced Aß-specific lamin protein cleavage, caspase-3/7-like DEVDase activation, and high cytotoxicity (5-10-fold higher than that induced by the wild-type oligomeric preparations). Oligomeric species enrichment and double treatment were not necessary for enhancing the cytotoxicity and intracellular location of the fusion peptide. Taiwaniaflavone, an inhibitor of the cytotoxicity of wild-type Aß42 and tAß42, strongly blocked the internalization of the peptides into the cells. These data imply a strong relationship between the cytotoxicity and intracellular location of the Aß peptide. Based on these results, we suggest that agents that can reduce the cell permeability of Aß42 are potential AD therapeutics.

Recognition of human emotions using EEG signals: A review.

Assessment of the cognitive functions and state of clinical subjects is an important aspect of e-health care delivery, and in the development of novel human-machine interfaces. A subject can display a range of emotions that significantly influence cognition, and emotion classification through the analysis of physiological signals is a key means of detecting emotion. Electroencephalography (EEG) signals have become a common focus of such development compared to other physiological signals because EEG employs simple and subject-acceptable methods for obtaining data that can be used for emotion analysis. We have therefore reviewed published studies that have used EEG signal data to identify possible interconnections between emotion and brain activity. We then describe theoretical conceptualization of basic emotions, and interpret the prevailing techniques that have been adopted for feature extraction, selection, and classification. Finally, we have compared the outcomes of these recent studies and discussed the likely future directions and main challenges for researchers developing EEG-based emotion analysis methods.

Differential involvement of caspase-6 in amyloid-ß-induced fragmentation of lamin A and B.

Amyloid-ß (Aß), a peptide implicated in Alzheimer's disease, was shown to cause specific fragmentation of lamin proteins, which was mediated by an unidentified protease named nuclear scaffold protease (NSP) independently of caspase-6. Because caspase-6 is responsible for the fragmentation process in many other damage-induced apoptosis, here we further investigated possible involvement of caspase-6 in Aß-induced lamin fragmentation under various conditions. We found that lamin A fragment generated by NSP (named fragment b) disappeared in cells incubated with Aß42 for prolonged periods and this product was preserved by a caspase-6 inhibitor. Furthermore, caspase-6 could remove fragment b in nuclei isolated from Aß42-treated cells (ANU). Lamin B in ANU was fragmented by caspase-6 only after treatment with an alkaline phosphatase. The caspase-mediated fragmentation of lamin B was also achieved with nuclei isolated from cells incubated with Aß42 plus a Cdk5 inhibitor. The results indicate that Aß42 induces NSP-mediated fragmentation of lamin A and the following removal process of fragment b by caspase-6 and an Aß-induced phosphorylation prevents the fragmentation of lamin B by caspase-6. The pathway leading to lamin protein fragmentation in this investigation appears to be specific for Aß and thus the data will provide novel insights into the toxicity of the peptide.

Design and Implementation of High-Performance ECC Processor with Unified Point Addition on Twisted Edwards Curve.

With the swift evolution of wireless technologies, the demand for the Internet of Things (IoT) security is rising immensely. Elliptic curve cryptography (ECC) provides an attractive solution to fulfill this demand. In recent years, Edwards curves have gained widespread acceptance in digital signatures and ECC due to their faster group operations and higher resistance against side-channel attacks (SCAs) than that of the Weierstrass form of elliptic curves. In this paper, we propose a high-speed, low-area, simple power analysis (SPA)-resistant field-programmable gate array (FPGA) implementation of ECC processor with unified point addition on a twisted Edwards curve, namely Edwards25519. Efficient hardware architectures for modular multiplication, modular inversion, unified point addition, and elliptic curve point multiplication (ECPM) are proposed. To reduce the computational complexity of ECPM, the ECPM scheme is designed in projective coordinates instead of affine coordinates. The proposed ECC processor performs 256-bit point multiplication over a prime field in 198,715 clock cycles and takes 1.9 ms with a throughput of 134.5 kbps, occupying only 6543 slices on Xilinx Virtex-7 FPGA platform. It supports high-speed public-key generation using fewer hardware resources without compromising the security level, which is a challenging requirement for IoT security.

Parallel point-multiplication architecture using combined group operations for high-speed cryptographic applications.

In this paper, we propose a novel parallel architecture for fast hardware implementation of elliptic curve point multiplication (ECPM), which is the key operation of an elliptic curve cryptography processor. The point multiplication over binary fields is synthesized on both FPGA and ASIC technology by designing fast elliptic curve group operations in Jacobian projective coordinates. A novel combined point doubling and point addition (PDPA) architecture is proposed for group operations to achieve high speed and low hardware requirements for ECPM. It has been implemented over the binary field which is recommended by the National Institute of Standards and Technology (NIST). The proposed ECPM supports two Koblitz and random curves for the key sizes 233 and 163 bits. For group operations, a finite-field arithmetic operation, e.g. multiplication, is designed on a polynomial basis. The delay of a 233-bit point multiplication is only 3.05 and 3.56 µs, in a Xilinx Virtex-7 FPGA, for Koblitz and random curves, respectively, and 0.81 µs in an ASIC 65-nm technology, which are the fastest hardware implementation results reported in the literature to date. In addition, a 163-bit point multiplication is also implemented in FPGA and ASIC for fair comparison which takes around 0.33 and 0.46 µs, respectively. The area-time product of the proposed point multiplication is very low compared to similar designs. The performance ([Formula: see text]) and Area × Time × Energy (ATE) product of the proposed design are far better than the most significant studies found in the literature.