Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury

Dirac semimetal PdTe2 temperature-dependent quasiparticle dynamics and electron-phonon coupling

Dirac semimetal PdTe2 single-crystal temperature-dependent ultrafast carrier and phonon dynamics were studied using ultrafast optical pump-probe spectroscopy. Two distinct carrier and coherent phonons relaxation processes were identified in the 5 K - 300 K range. Quantitative analysis revealed a fast relaxation process ({\tau}_f) occurring on a subpicosecond time scale which originated from electron-phonon thermalization. This was followed by a slower relaxation process ({\tau}_s) with a time scale of ~ 7-9.5 ps which originated from phonon-assisted electron-hole recombination. Two significant vibrational modes resolved at all measured temperatures and corresponded to Te atoms in-plane (E_g), and out-of-plane (A_1g), motion. As temperature increased both phonon modes softened markedly. A_1g mode frequency monotonically decreased as temperature increased. Its damping rate remained virtually unchanged. As expected, E_g decreased uniformly as temperatures rose. At temperatures above 80 K, there was insignificant change. Test results suggested that pure dephasing played an important role in the relaxation processes. PdTe2 phonon is thought responsible for its superconductive properties. Examining phonons behavior should improve the understanding of its complex superconductivity.Comment: 6 pages, 4 figure

Bioengineered human tissue regeneration and repair using endogenous stem cells

We describe a general approach to produce bone and cartilaginous structures utilizing the self-regenerative capacity of the intercostal rib space to treat a deformed metacarpophalangeal joint and microtia. Anatomically precise 3D molds were positioned on the perichondro-periosteal or perichondral flap of the intercostal rib without any other exogenous elements. We find anatomically precise metacarpal head and auricle constructs within the implanted molds after 6 months. The regenerated metacarpal head was used successfully to surgically repair the deformed metacarpophalangeal joint. Auricle reconstructive surgery in five unilateral microtia patients yielded good aesthetic and functional results. Long-term follow-up revealed the auricle constructs were safe and stable. Single-cell RNA sequencing analysis reveal early infiltration of a cell population consistent with mesenchymal stem cells, followed by IL-8-stimulated differentiation into chondrocytes. Our results demonstrate the repair and regeneration of tissues using only endogenous factors and a viable treatment strategy for bone and tissue structural defects.</p

Experimental Quantum Simulation of Dynamic Localization on Curved Photonic Lattices

Dynamic localization, which originates from the phenomena of particle evolution suppression under an externally applied AC electric field, has been simulated by suppressed light evolution in periodically-curved photonic arrays. However, experimental studies on their quantitative dynamic transport properties and application for quantum information processing are rare. Here we fabricate one-dimensional and hexagonal two-dimensional arrays, both with sinusoidal curvature. We successfully observe the suppressed single-photon evolution patterns, and for the first time measure the variances to study their transport properties. For one-dimensional arrays, the measured variances match both the analytical electric field calculation and the quantum walk Hamiltonian engineering approach. For hexagonal arrays, as anisotropic effective couplings in four directions are mutually dependent, the analytical approach suffers, while quantum walk conveniently incorporates all anisotropic coupling coefficients in the Hamiltonian and solves its exponential as a whole, yielding consistent variances with our experimental results. Furthermore, we implement a nearly complete localization to show that it can preserve both the initial injection and the wave-packet after some evolution, acting as a memory of a flexible time scale in integrated photonics. We demonstrate a useful quantum simulation of dynamic localization for studying their anisotropic transport properties, and a promising application of dynamic localization as a building block for quantum information processing in integrated photonics.Comment: 4 figure

Eutypellaolides A–J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively

The Litsea genome and the evolution of the laurel family

The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents