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Environment International Jun 2024Fusion energy investigation has stepped to a new stage adopting deuterium and tritium as fuels from the previous stage concentrating hydrogen plasma physics. Special... (Review)
Review
Fusion energy investigation has stepped to a new stage adopting deuterium and tritium as fuels from the previous stage concentrating hydrogen plasma physics. Special radiation safety issues would be introduced during this stage. In addition to industrial and military uses, tungsten is also regarded as the most promising plasma facing material for fusion reactors. During the operation of fusion reactors, tungsten-based plasma facing materials can be activated via neutron nuclear reaction. Meanwhile, activated tungsten dust can be produced when high-energy plasma interacts with the tungsten-based plasma facing materials, namely plasma wall interaction. Activated tungsten dust would be an emerging environmental pollutant with radiation toxicity containing various radionuclides in addition to the chemical toxicity of tungsten itself. Nonetheless, the historical underestimation of its environmental availability has led to limited research on tungsten compared to other environmental contaminants. This paper presents the first systematic review on the safety issue of emerging activated tungsten dust, encompassing source terms, environmental behaviors, and health effects. The key contents are as follows: 1) to detail the source terms of activated tungsten dust from aspects of tungsten basic properties, generation mechanism, physical morphology and chemical component, radioactivity, as well as potential release pathways, 2) to illustrate the environmental behaviors from aspects of atmospheric dispersion and deposition, transformation and migration in soil, as well as plant absorption and distribution, 3) to identify the toxicity and health effects from aspects of toxicity to plants, distribution in human body, as well as health effects by radiation and chemical toxicity, 4) based on the research progress, research and development issues needed are also pointed out to better knowledge of safety issue of activated tungsten dust, which would be beneficial to the area of fusion energy and ecological impact caused by the routine tungsten related industrial and military applications.
Topics: Tungsten; Dust; Humans
PubMed: 38810497
DOI: 10.1016/j.envint.2024.108774 -
Chemical Science Sep 2023Cucurbit[7]uril (CB[7]) encapsulates adamantyl and trimethylsilyl substituents of positively charged guests in dimethyl sulfoxide (DMSO). Unlike in water or deuterium...
Cucurbit[7]uril (CB[7]) encapsulates adamantyl and trimethylsilyl substituents of positively charged guests in dimethyl sulfoxide (DMSO). Unlike in water or deuterium oxide, addition of a selection of alkali and alkali-earth cations with van der Waals radii between 1.0 and 1.4 Å (Na, K, Ca, Sr, Ba and Eu) to the CB[7]/guest complexes triggers their cation-mediated trimerization, a process that is very slow on the nuclear magnetic resonance (NMR) time scale. Smaller (Li, Mg) or larger cations (Rb, Cs or NH) are inert. The trimers display extensive CH-O interactions between the equatorial and pseudo-equatorial hydrogens of CB[7] and the carbonyl rim of the neighboring CB[7] unit in the trimer, and a deeply nested cation between the three interacting carbonylated CB[7] rims; a counteranion is likely perched in the shallow cavity formed by the three outer walls of CB[7] in the trimer. Remarkably, a guest must occupy the cavity of CB[7] for trimerization to take place. Using a combination of semi-empirical and density functional theory techniques in conjunction with continuum solvation models, we showed that trimerization is favored in DMSO, and not in water, because the penalty for the partial desolvation of three of the six CB[7] portals upon aggregation into a trimer is less unfavorable in DMSO compared to water.
PubMed: 37712024
DOI: 10.1039/d3sc02032k -
BioRxiv : the Preprint Server For... Oct 2023The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain...
UNLABELLED
The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain incompletely understood. The ABCC transporters core consists of two nucleotide binding domains (NBD1,2) and transmembrane domains (TMD1,2). Using molecular dynamic simulations, biochemical and hydrogen deuterium exchange approaches, we show that the mutational uncoupling or stabilization of NBD1-TMD1/2 interfaces can compromise or facilitate the CFTR(ABCC7)-, MRP1(ABCC1)-, and ABCC6-transporters posttranslational coupled domain-folding in the endoplasmic reticulum. Allosteric or orthosteric binding of VX-809 and/or VX-445 folding correctors to TMD1/2 can rescue kinetically trapped CFTR post-translational folding intermediates of cystic fibrosis (CF) mutants of NBD1 or TMD1 by global rewiring inter-domain allosteric-networks. We propose that dynamic allosteric domain-domain communications not only regulate ABCC-transporters function but are indispensable to tune the folding landscape of their post-translational intermediates. These allosteric networks can be compromised by CF-mutations, and reinstated by correctors, offering a framework for mechanistic understanding of ABCC-transporters (mis)folding.
ONE-SENTENCE SUMMARY
Allosteric interdomain communication and its modulation are critical determinants of ABCC-transporters post-translational conformational biogenesis, misfolding, and pharmacological rescue.
PubMed: 37905074
DOI: 10.1101/2023.10.19.563107 -
Anais Da Academia Brasileira de Ciencias 2023A 22.48 m long ice core (BR-IC-4) was collected in the West Antarctic Ice Sheet (at 83°58'59.4" S, 80°07'01.4" W, 1,295 m above the sea level) during the Austral...
A 22.48 m long ice core (BR-IC-4) was collected in the West Antarctic Ice Sheet (at 83°58'59.4" S, 80°07'01.4" W, 1,295 m above the sea level) during the Austral summer of 2004-2005, as a contribution to the International Trans-Antarctic Expedition program. The isotopic composition (δD and δ18O) of 599 samples, corresponding to the upper 12.98 m of the ice core, was determined by gas source mass spectrometry and cavity ring-down spectroscopy. Relative dating was based on the isotopic ratios and major ions (MS-, Na+, nssSO4 2-) and trace elements (Na, S, Sr) concentrations. The record covers approximately 13 years - from 1990 to 2003. The mean accumulation rate of 0.48 ± 0.09 m water equivalent per year (m eq H2O a1) is relatively high for the geographical area and possibly results from snowdrifting from near areas, as attested by ice glaze surfaces in other sites in the region. The stable isotope δD content varies between -367.90‰ and 256.30‰ (mean -314.42 ± 19.01‰); and δ18O ranges from -44.96‰ to 35.08‰ (mean -39.95 ± 2.05‰). Deuterium excess values (mean 3.70 ± 1.54‰) indicate episodic intense oceanic evaporation and high relative humidity in the moisture sources.
Topics: Antarctic Regions; Oxygen Isotopes; Mass Spectrometry; Seasons; Water
PubMed: 38126378
DOI: 10.1590/0001-3765202320230132 -
Life Science Alliance Feb 2024GRP94, an ER paralog of the heat-shock protein 90 family, binds and hydrolyses ATP to chaperone the folding and maturation of its selected clients. Compared with other...
GRP94, an ER paralog of the heat-shock protein 90 family, binds and hydrolyses ATP to chaperone the folding and maturation of its selected clients. Compared with other hsp90 proteins, the in-solution conformational dynamics of GRP94 along the ATP hydrolysis cycle are less understood, hindering our understanding of its chaperoning mechanism. Leveraging small-angle X-ray scattering, negative-staining EM, and hydrogen-deuterium exchange coupled mass-spec, here we show that in its apo form, ∼60% of mouse GRP94 (mGRP94) populates an "extended" conformation, whereas the rest exist in either "close V" or "twist V" like "compact" conformations. Different from other hsp90 proteins, the presence of AMPPNP only impacts the relative abundance of the two compact conformations, rather than shifting the equilibrium between the "extended" and "compact" conformations of mGRP94. HDX-MS study of apo, AMPPNP-bound, and ADP-bound mGRP94 suggests a conformational transition from "twist V" to "close V" upon ATP binding and a back transition from "close V" to "twist V" upon ATP hydrolysis. These results illustrate the dissimilarities of GRP94 in conformation transition during ATP hydrolysis from other hsp90 paralogs.
Topics: Animals; Mice; Adenylyl Imidodiphosphate; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Membrane Proteins; Molecular Chaperones; Protein Conformation
PubMed: 37949474
DOI: 10.26508/lsa.202302051 -
Advanced Science (Weinheim,... Aug 2023Gas-solid reactions are important for many redox processes that underpin the energy and sustainability transition. The specific case of hydrogen-based iron oxide...
Gas-solid reactions are important for many redox processes that underpin the energy and sustainability transition. The specific case of hydrogen-based iron oxide reduction is the foundation to render the global steel industry fossil-free, an essential target as iron production is the largest single industrial emitter of carbon dioxide. This perception of gas-solid reactions has not only been limited by the availability of state-of-the-art techniques which can delve into the structure and chemistry of reacted solids, but one continues to miss an important reaction partner that defines the thermodynamics and kinetics of gas phase reactions: the gas molecules. In this investigation, cryogenic-atom probe tomography is used to study the quasi in situ evolution of iron oxide in the solid and gas phases of the direct reduction of iron oxide by deuterium gas at 700°C. So far several unknown atomic-scale characteristics are observed, including, D accumulation at the reaction interface; formation of a core (wüstite)-shell (iron) structure; inbound diffusion of D through the iron layer and partitioning of D among phases and defects; outbound diffusion of oxygen through the wüstite and/or through the iron to the next free available inner/outer surface; and the internal formation of heavy nano-water droplets at nano-pores.
PubMed: 37290039
DOI: 10.1002/advs.202300626 -
Nature Communications Aug 2023Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals. Although methods for the synthesis of indole alkaloids...
Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals. Although methods for the synthesis of indole alkaloids are constantly explored, the direct single-step synthesis of these chemical entities with broad structural diversity remains a formidable challenge. Herein, we report a modular assembly of tetrahydrocarboline type of indole alkaloids from simple building blocks in a single step while showing broad compatibility with medicinally relevant functionality. In this protocol, the 2-alkylated or 3-alkylated indoles, formaldehyde, and amine hydrochlorides could undergo a one-pot reaction to deliver γ-tetrahydrocarbolines or β-tetrahydrocarbolines directly. A wide scope of these readily available starting materials is applicable in this process, and numerous structural divergent tetrahydrocarbolines could be achieved rapidly. The control reaction and deuterium-labelling reaction are conducted to probe the mechanism. And mechanistically, this multicomponent reaction relies on a multiple alkylamination cascade wherein an unusual C(sp)-C(sp) connection was involved in this process. This method could render rapid access to pharmaceutically interesting compounds, greatly enlarge the indole alkaloid library and accelerate the lead compound optimization thus facilitating drug discovery.
PubMed: 37558669
DOI: 10.1038/s41467-023-40598-y -
ELife Mar 2024The physical basis of phase separation is thought to consist of the same types of bonds that specify conventional macromolecular interactions yet is unsatisfyingly often...
The physical basis of phase separation is thought to consist of the same types of bonds that specify conventional macromolecular interactions yet is unsatisfyingly often referred to as 'fuzzy'. Gaining clarity on the biogenesis of membraneless cellular compartments is one of the most demanding challenges in biology. Here, we focus on the chromosome passenger complex (CPC), that forms a chromatin body that regulates chromosome segregation in mitosis. Within the three regulatory subunits of the CPC implicated in phase separation - a heterotrimer of INCENP, Survivin, and Borealin - we identify the contact regions formed upon droplet formation using hydrogen/deuterium exchange mass spectrometry (HXMS). These contact regions correspond to some of the interfaces seen between individual heterotrimers within the crystal lattice they form. A major contribution comes from specific electrostatic interactions that can be broken and reversed through initial and compensatory mutagenesis, respectively. Our findings reveal structural insight for interactions driving liquid-liquid demixing of the CPC. Moreover, we establish HXMS as an approach to define the structural basis for phase separation.
Topics: Phase Separation; Cell Cycle Proteins; Chromosomes; Mitosis; Cytoskeleton; Chromosome Segregation; Aurora Kinase B
PubMed: 38456462
DOI: 10.7554/eLife.92709 -
Gut Microbes Dec 2023Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal...
Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of and , and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.
Topics: Infant; Female; Humans; Breast Feeding; Gastrointestinal Microbiome; Milk, Human; Microbiota; Oligosaccharides; Metabolome
PubMed: 37741856
DOI: 10.1080/19490976.2023.2257273 -
European Journal of Pharmaceutical... Aug 2023The discovery of cephalosporin and demonstration of its improved stability in aqueous solution, as well as enhanced in vitro activity against penicillin-resistant...
The discovery of cephalosporin and demonstration of its improved stability in aqueous solution, as well as enhanced in vitro activity against penicillin-resistant organisms, were major breakthroughs in the development of β-lactam antibiotics. Although cephalosporins are more stable with respect to hydrolytic degradation than penicillins, they still experience a variety of chemical transformations. The present study offers an insight into the rates and mechanisms of ceftriaxone degradation at the therapeutic concentration in water, a mixture of water and deuterium oxide, and deuterium oxide itself at the neutral pH. Specific ceftriaxone degradation products were observed in aged samples (including a previously unreported dimer-type species), and by comparing the degradation rates in HO and DO, the observation of a kinetic isotope effect provided some valuable insight as to the nature of the initial ceftriaxone degradation. The effect of protium to deuterium isotope change on the degradation kinetics of ceftriaxone was evaluated using the method of initial rates based on HPLC analysis as well as by quantitative H NMR spectroscopy. Moreover, computational analysis was utilized to get a molecular insight into chemical processes governing the ceftriaxone degradation and to rationalize the stabilizing effect of replacing HO with DO.
Topics: Deuterium Oxide; Deuterium; Ceftriaxone; Kinetics; Water; Cephalosporins
PubMed: 37160178
DOI: 10.1016/j.ejps.2023.106461