Renal protective effects of vicenin-2 and scolymoside in a mouse model of sepsis

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata—vicenin-2 (VCN) and scolymoside (SCL)—could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury

A Multi-dimensional Deep Structured State Space Approach to Speech Enhancement Using Small-footprint Models

We propose a multi-dimensional structured state space (S4) approach to speech enhancement. To better capture the spectral dependencies across the frequency axis, we focus on modifying the multi-dimensional S4 layer with whitening transformation to build new small-footprint models that also achieve good performance. We explore several S4-based deep architectures in time (T) and time-frequency (TF) domains. The 2-D S4 layer can be considered a particular convolutional layer with an infinite receptive field although it utilizes fewer parameters than a conventional convolutional layer. Evaluated on the VoiceBank-DEMAND data set, when compared with the conventional U-net model based on convolutional layers, the proposed TF-domain S4-based model is 78.6% smaller in size, yet it still achieves competitive results with a PESQ score of 3.15 with data augmentation. By increasing the model size, we can even reach a PESQ score of 3.18.Comment: Accepted to Interspeech 2023. Code will be released at https://github.com/Kuray107/S4ND-U-Net_speech_enhancemen

Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P

The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1α, IL-1β, TNF-α, TNF-β, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment

Atomic layer coating of hafnium oxide on carbon nanotubes for high-performance field emitters

Carbon nanotubes coated with hafnium oxide exhibit excellent electron emission characteristics, including a low turn-on voltage, a high field enhancement factor, and exceptional current stability. Their enhanced emission performance was attributed to a decrease in the work function and an increase in the electron density of states at the carbon nanotube Fermi level closest to the conduction band minimum of hafnium oxide. In addition, the enhanced current stability was attributed to the ability of hafnium oxide to protect the carbon nanotubes against ions and free radicals created in the electron field emission process. (C) 2011 American Institute of Physics. [doi:10.1063/1.3650471]ArticleAPPLIED PHYSICS LETTERS. 99(15):153115 (2011)journal articl

Amyloid-β peptide induces oligodendrocyte death by activating the neutral sphingomyelinase–ceramide pathway

Amyloid-β peptide (Aβ) accumulation in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration. We have recently demonstrated that Aβ induced oligodendrocyte (OLG) apoptosis, suggesting a role in white matter pathology in AD. Here, we explore the molecular mechanisms involved in Aβ-induced OLG death, examining the potential role of ceramide, a known apoptogenic mediator. Both Aβ and ceramide induced OLG death. In addition, Aβ activated neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase, resulting in increased ceramide generation. Blocking ceramide degradation with N-oleoyl-ethanolamine exacerbated Aβ cytotoxicity; and addition of bacterial sphingomyelinase (mimicking cellular nSMase activity) induced OLG death. Furthermore, nSMase inhibition by 3-O-methyl-sphingomyelin or by gene knockdown using antisense oligonucleotides attenuated Aβ-induced OLG death. Glutathione (GSH) precursors inhibited Aβ activation of nSMase and prevented OLG death, whereas GSH depletors increased nSMase activity and Aβ-induced death. These results suggest that Aβ induces OLG death by activating the nSMase–ceramide cascade via an oxidative mechanism

DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation

Dengue fever (DF) is an arthropod-borne disease that is prevalent in tropical and subtropical regions of the world. DC-SIGN [dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin] is a major receptor for dengue infection. DC-SIGN, also called CD209, expresses on dendritic cells (DCs) that bind to ICAM-3, which is expressed on T cells to facilitate the initial interaction between DCs and T cells. Variations in the CD209 promoter (−336 A/G; rs4804803) genotype are involved in the pathogenesis of human infectious diseases. Here we found that patients with dengue hemorrhagic fever (DHF) had a higher frequency of the AG or GG genotype of rs4804803 than DF or controls. Functional studies determined that monocyte-derived DCs (MDDCs) from individuals with AG genotype had significantly higher cell surface DC-SIGN expression, associated with higher TNFα, IL-12p40, and IP-10 production, but lower viral replication than those with AA genotype. An increase in DEN-2 replication in MDDCs was observed following the addition of anti-IP-10 neutralizing antibody. These findings highlight the fact that the rs4804803 SNP in the CD209 promoter is associated with DHF and correlated to DC-SIGN expression and immune augmentation

Coupling of spin and orbital excitations in the iron-based superconductor FeSe(0.5)Te(0.5)

We present a combined analysis of neutron scattering and photoemission measurements on superconducting FeSe(0.5)Te(0.5). The low-energy magnetic excitations disperse only in the direction transverse to the characteristic wave vector (1/2,0,0), whereas the electronic Fermi surface near (1/2,0,0) appears to consist of four incommensurate pockets. While the spin resonance occurs at an incommensurate wave vector compatible with nesting, neither spin-wave nor Fermi-surface-nesting models can describe the magnetic dispersion. We propose that a coupling of spin and orbital correlations is key to explaining this behavior. If correct, it follows that these nematic fluctuations are involved in the resonance and could be relevant to the pairing mechanism.Comment: 4 pages, 4 figures; accepted versio