Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation.

Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.

Comment on "Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity" Antioxidants 2020, 9, 594.

We have with enthusiasm read the article "Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity"[...].

Evidence that fodipir (DPDP) binds neurotoxic Pt2+ with a high affinity: An electron paramagnetic resonance study.

Oxaliplatin typically causes acute neuropathic problems, which may, in a dose-dependent manner, develop into a chronic form of chemotherapy-induced peripheral neuropathy (CIPN), which is associated with retention of Pt2+ in the dorsal root ganglion. A clinical study by Coriat and co-workers suggests that co-treatment with mangafodipir [Manganese(II) DiPyridoxyl DiPhosphate; MnDPDP] cures ongoing CIPN. These authors anticipated that it is the manganese superoxide dismutase mimetic activity of MnDPDP that explains its curative activity. However, this is questionable from a pharmacokinetic perspective. Another, but until recently undisclosed possibility is that Pt2+ outcompetes Mn2+/Ca2+/Zn2+ for binding to DPDP or its dephosphorylated metabolite PLED (diPyridoxyL EthylDiamine) and transforms toxic Pt2+ into a non-toxic complex, which can be readily excreted from the body. We have used electron paramagnetic resonance guided competition experiments between MnDPDP (10logKML ≈ 15) and K2PtCl4, and between MnDPDP and ZnCl2 (10logKML ≈ 19), respectively, in order to obtain an estimate the 10logKML of PtDPDP. Optical absorption spectroscopy revealed a unique absorption line at 255 nm for PtDPDP. The experimental data suggest that PtDPDP has a higher formation constant than that of ZnDPDP, i.e., higher than 19. The present results suggest that DPDP/PLED has a high enough affinity for Pt2+ acting as an efficacious drug in chronic Pt2+-associated CIPN.

Band Structure of Wurtzite GaBiAs Nanowires.

We report on the first successful growth of wurtzite (WZ) GaBiAs nanowires (NWs) and reveal the effects of Bi incorporation on the electronic band structure by using polarization-resolved optical spectroscopies performed on individual NWs. Experimental evidence of a decrease in the band-gap energy and an upward shift of the topmost three valence subbands upon the incorporation of Bi atoms is provided, whereas the symmetry and ordering of the valence band states remain unchanged, that is, Γ9, Γ7, and Γ7 within the current range of Bi compositions. The extraordinary valence band structure of WZ GaBiAs NWs is explained by anisotropic hybridization and anticrossing between p-like Bi states and the extended valence band states of host WZ GaAs. Moreover, the incorporation of Bi into GaAs is found to significantly reduce the temperature sensitivity of the band-gap energy in WZ GaBiAs NWs. Our work therefore demonstrates that utilizing dilute bismide alloys provides new avenues for band-gap engineering and thus photonic engineering with NWs.

Low-Loss and Tunable Localized Mid-Infrared Plasmons in Nanocrystals of Highly Degenerate InN.

Plasmonic response of free charges confined in nanostructures of plasmonic materials is a powerful means for manipulating the light-material interaction at the nanoscale and hence has influence on various relevant technologies. In particular, plasmonic materials responsive in the mid-infrared range are technologically important as the mid-infrared is home to the vibrational resonance of molecules and also thermal radiation of hot objects. However, the development of the field is practically challenged with the lack of low-loss materials supporting high quality plasmons in this range of the spectrum. Here, we demonstrate that degenerately doped InN nanocrystals (NCs) support tunable and low-loss plasmon resonance spanning the entire midwave infrared range. Modulating free-carrier concentration is achieved by engineering nitrogen-vacancy defects (InN1- x, 0.017 < x < 0.085) in highly degenerate NCs using a nonequilibrium gas-phase growth process. Despite the significant reduction in the carrier mobility relative to intrinsic InN, the mobility in degenerate InN NCs (>60 cm2/(V s)) remains considerably higher than the carrier mobility reported for other materials NCs such as doped metal oxides, chalcogenides, and noble metals. These findings demonstrate feasibility of controlled tuning of infrared plasmon resonances in a low-loss material of III-V compounds and open a gateway to further studies of these materials nanostructures for infrared plasmonic applications.

Pretreatment of anaerobic digester samples by hydrochloric acid for solution-state 1H and 13C NMR spectroscopic characterization of organic matter.

Pretreatment of anaerobic digester samples by hydrochloric acid (HCl) resulted in removal of Fe-based mineral and coordination compounds, attenuating their interferences with solution-state nuclear magnetic resonance (NMR) spectroscopic characterization of the solid phase organic matter. Substrate (influent) and digestate (effluent) samples from two full-scale anaerobic digesters, designated CD (co-digester) and SSD (sewage sludge digester), were investigated. Pretreatment of CD samples with 0.2-2.0 mol l-1 HCl and pretreatment of SSD samples with 1.0-3.0 mol l-1 HCl removed 96-100% and 76-80% of total Fe, respectively. Pretreatment declined overall paramagnetic characteristics of digestate samples, manifested by 50% (CD) and 70% (SSD) decrease in electron paramagnetic resonance signal intensities. As a result, meaningful solution-state 1H,13C heteronuclear single quantum coherence and 1H NMR spectra of DMSO-d6 soluble organic matter could be acquired. Sample pretreatment with the lowest concentration of HCl resulted in alteration of C:N ratios in solid phase, likely due to removal of labile organic and inorganic C- and N-containing compounds, while elevating the HCl concentration did not further change the C:N ratios. Furthermore, sample pretreatment increased the solubility of carbohydrates and proteins in DMSO-d6, enabling the detection of NMR resonances from certain structural units of carbohydrates (e.g. anomeric O2CH) and proteins (e.g. CHα in amino acids). Both attenuation of the paramagnetic matrix as well as an enhanced solubility of carbohydrate and protein fractions of the samples in DMSO-d6 solvent contributed to an improved molecular characterization of anaerobic digester samples by solution-state NMR analysis.

Room-temperature InP/InAsP Quantum Discs-in-Nanowire Infrared Photodetectors.

The possibility to engineer nanowire heterostructures with large bandgap variations is particularly interesting for technologically important broadband photodetector applications. Here we report on a combined study of design, fabrication, and optoelectronic properties of infrared photodetectors comprising four million n+-i-n+ InP nanowires periodically ordered in arrays. The nanowires were grown by metal-organic vapor phase epitaxy on InP substrates, with either a single or 20 InAsP quantum discs embedded in the i-segment. By Zn compensation of the residual n-dopants in the i-segment, the room-temperature dark current is strongly suppressed to a level of pA/NW at 1 V bias. The low dark current is manifested in the spectrally resolved photocurrent measurements, which reveal strong photocurrent contributions from the InAsP quantum discs at room temperature with a threshold wavelength of about 2.0 µm and a bias-tunable responsivity reaching 7 A/W@1.38 µm at 2 V bias. Two different processing schemes were implemented to study the effects of radial self-gating in the nanowires induced by the nanowire/SiOx/ITO wrap-gate geometry. Summarized, our results show that properly designed axial InP/InAsP nanowire heterostructures are promising candidates for broadband photodetectors.