Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To ...explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 μM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 μM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 μM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 μM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 μM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.
Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro (Created with BioRender.com). Display omitted
•Ferroptosis was associated with TDCPP-induced neurotoxicity.•TDCPP-induced ferroptosis might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.•TDCPP induced mitochondrial depolarization via the VDAC channels activation.
Abstract
Ruthenium exhibits comparable or even better alkaline hydrogen evolution reaction activity than platinum, however, the mechanistic aspects are yet to be settled, which are elucidated by ...combining in situ Raman spectroscopy and theoretical calculations herein. We simultaneously capture dynamic spectral evidence of Ru surfaces, interfacial water, *H and *OH intermediates. Ru surfaces exist in different valence states in the reaction potential range, dissociating interfacial water differently and generating two distinct *H, resulting in different activities. The local cation tuning effect of hydrated Na
+
ion water and the large work function of high-valence Ru(n+) surfaces promote interfacial water dissociation. Moreover, compared to low-valence Ru(0) surfaces, high-valence Ru(n+) surfaces have more moderate adsorption energies for interfacial water, *H, and *OH. They, therefore, facilitate the activity. Our findings demonstrate the regulation of valence state on interfacial water, intermediates, and finally the catalytic activity, which provide guidelines for the rational design of high-efficiency catalysts.
Oilseed rape (Brassica napus L.) is the second highest yielding oil crop worldwide. In addition to being used as an edible oil and a feed for livestock, rapeseed has high ornamental value. In this ...study, we identified and characterized the main floral major constituents, including phenolic acids and flavonoids components, in rapeseed accessions with different-colored petals. A total of 144 constituents were identified using ultrahigh-performance liquid chromatography–HESI-mass spectrometry (UPLC–HESI-MS/MS), 57 of which were confirmed and quantified using known standards and mainly contained phenolic acids, flavonoids, and glucosinolates compounds. Most of the epicatechin, quercetin, and isorhamnetin derivates were found in red and pink petals of B. napus, while kaempferol derivates were in yellow and pale white petals. Moreover, petal-specific compounds, including a putative hydroxycinnamic acid derivative, sinapoyl malate, 1-O-sinapoyl-β-d-glucose, feruloyl glucose, naringenin-7-O-glucoside, cyanidin-3-glucoside, cyanidin-3,5-di-O-glucoside, petunidin-3-O-β-glucopyranoside, isorhamnetin-3-O-glucoside, kaempferol-3-O-glucoside-7-O-glucoside, quercetin-3,4′-O-di-β-glucopyranoside, quercetin-3-O-glucoside, and delphinidin-3-O-glucoside, might contribute to a variety of petal colors in B. napus. In addition, bound phenolics were tentatively identified and contained three abundant compounds (p-coumaric acid, ferulic acid, and 8-O-4′-diferulic acid). These results provide insight into the molecular mechanisms underlying petal color and suggest strategies for breeding rapeseed with a specific petal color in the future.
The sirtuin family in health and disease Wu, Qi-Jun; Zhang, Tie-Ning; Chen, Huan-Huan ...
Signal transduction and targeted therapy,
12/2022, Volume:
7, Issue:
1
Journal Article
Peer reviewed
Open access
Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological ...processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.
Rubber composites with excellent radiation shielding and flexibility are extremely important to personal protective equipments (PPEs) for protecting workers from radiation hazards, especially for ...mixed radiations. It is, however, challenging to achieve uniform dispersion of fillers and good compatibility of the interfaces in highly‐filled rubber composites that are closely related to their physical properties. In this article, lead borate@polydopamine (PBO@PDA) core–shell particles are chemically bonded with silicone rubber (SR) for co‐shielding of neutron and γ‐rays. Uniform dispersion of the core–shell particles and good compatibility of the interfaces give rise to enhanced flexibility of the rubber composites. Particularly, the SR composite with 40 wt% PBO particles displays increases of 106% in elongation at break and 490% in tensile strength to neat SR. Furthermore, the mass attenuation coefficient of γ‐rays (105 KeV) reaches 2.35 and the thermal neutron absorption rate (0.025 eV) of is 76.9%. This work takes into account the balance between radiation shielding and flexibility of rubber composites, which provides a facile strategy to fabricate excellent integrated properties of flexible materials for shielding mixed neutron and γ‐rays.
Lead borate micro–nano particles chemically bonded with silicone rubber are used to coordinately shield thermal neutrons and gamma rays.
Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics ...and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.
Carotenoid cleavage dioxygenase (CCD), a key enzyme in carotenoid metabolism, cleaves carotenoids to form apo-carotenoids, which play a major role in plant growth and stress responses. CCD genes had ...not previously been systematically characterized in Brassica napus (rapeseed), an important oil crop worldwide. In this study, we identified 30 BnCCD genes and classified them into nine subgroups based on a phylogenetic analysis. We identified the chromosomal locations, gene structures, and cis-promoter elements of each of these genes and performed a selection pressure analysis to identify residues under selection. Furthermore, we determined the subcellular localization, physicochemical properties, and conserved protein motifs of the encoded proteins. All the CCD proteins contained a retinal pigment epithelial membrane protein (RPE65) domain. qRT-PCR analysis of expression of 20 representative BnCCD genes in 16 tissues of the B. napus cultivar Zhong Shuang 11 (‘ZS11’) revealed that members of the BnCCD gene family possess a broad range of expression patterns. This work lays the foundation for functional studies of the BnCCD gene family.
Flexible materials with excellent radiation shielding and flexibility are essential to the personal protective equipments (PPEs) for protecting workers from nuclear radiations. However, it is an ...enormous challenge to obtain the desired materials since high loading filler in polymer nanocomposites usually promotes radiation shielding while restrains its flexibility. Here, a facile “thiol‐ene click” means is applied to chemically bond high loading boron nitride (BN) nanoparticles with silicone rubber (SR) in SR/BN nanocomposites for thermal neutron shielding. Uniform dispersion of BN nanoparticles and good compatibility of interfaces in the nanocomposites with high loading filler lead to increased flexibility instead of decrease. In particular, the nanocomposite with 40 wt% BN displays 911% of elongation at break that is about 50% enhancement to that of neat SR. Furthermore, higher loading BN in the nanocomposites means better thermal neutron shielding. Namely, enhanced thermal neutron shielding and flexibility is achieved at SR/BN nanocomposite with 40 wt% BN. The present work provides a facile strategy towards superior integrated performance of flexible materials for radiation shielding, such as wearable devices.
Chemically bonding BN nanoparticles with silicone rubber contributes to good interfacial compatibility in highly‐filled polymer nanocomposites, leading to enhanced radiation shielding and flexibility.
is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for ...the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of
. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in
.
A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed
NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC
) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against
strains ranged from 64 to 128 μg/mL. Time-kill assays showed that myricetin was a bactericidal agent against
. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by
culture on rabbit erythrocytes in a dose-dependent manner.
Myricetin was newly discovered to be a competitive inhibitor of
NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.
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