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Cell Metabolism Jun 2024The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular...
The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (DO) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent stem cells (iPSCs). Transfer of unsaturated lipids from tauopathy iPSC neurons to microglia induced LD accumulation, oxidative stress, inflammation, and impaired phagocytosis. Neuronal AMP-activated protein kinase (AMPK) inhibits lipogenesis and promotes lipophagy in neurons, thereby reducing lipid flux to microglia. AMPK depletion in prodromal tauopathy mice increased LD accumulation, exacerbated pro-inflammatory microgliosis, and promoted neuropathology. Our findings provide direct evidence of native, aberrant LD accumulation in tauopathy brains and underscore the critical role of AMPK in regulating brain lipid homeostasis.
Topics: Animals; Lipid Droplets; Microglia; Humans; Mice; AMP-Activated Protein Kinases; Brain; Tauopathies; Neurons; Induced Pluripotent Stem Cells; Mice, Inbred C57BL; Male; Drosophila
PubMed: 38657612
DOI: 10.1016/j.cmet.2024.03.014 -
Plant & Cell Physiology Jun 2024Isotope labeling coupled with mass spectrometry imaging (MSI) presents a potent strategy for elucidating the dynamics of metabolism at cellular resolution, yet its...
Isotope labeling coupled with mass spectrometry imaging (MSI) presents a potent strategy for elucidating the dynamics of metabolism at cellular resolution, yet its application to plant systems is scarce. It has the potential to reveal the spatio-temporal dynamics of lipid biosynthesis during plant development. In this study, we explore its application to galactolipid biosynthesis of an aquatic plant, Lemna minor, with D2O labeling. Specifically, matrix-assisted laser desorption/ionization-MSI data of two major galactolipids in L. minor, monogalactosyldiacylglycerol and digalactosyldiacylglycerol, were studied after growing in 50% D2O media over a 15-day time period. When they were partially labeled after 5 d, three distinct binomial isotopologue distributions were observed corresponding to the labeling of partial structural moieties: galactose only, galactose and a fatty acyl chain and the entire molecule. The temporal change in the relative abundance of these distributions follows the expected linear pathway of galactolipid biosynthesis. Notably, their mass spectrometry images revealed the localization of each isotopologue group to the old parent frond, the intermediate tissues and the newly grown daughter fronds. Besides, two additional labeling experiments, (i) 13CO2 labeling and (ii) backward labeling of completely 50% D2O-labeled L. minor in H2O media, confirm the observations in forward labeling. Furthermore, these experiments unveiled hidden isotopologue distributions indicative of membrane lipid restructuring. This study suggests the potential of isotope labeling using MSI to provide spatio-temporal details in lipid biosynthesis in plant development.
Topics: Galactolipids; Isotope Labeling; Araceae; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Deuterium Oxide
PubMed: 38590126
DOI: 10.1093/pcp/pcae032 -
Journal of Colloid and Interface Science Jul 2024Piezo-photocatalytic water (deuterium oxide) decomposition is a promising strategy for realizing renewable energy, but the manipulation of the polar center remains a big...
Piezo-photocatalytic water (deuterium oxide) decomposition is a promising strategy for realizing renewable energy, but the manipulation of the polar center remains a big challenge. This study uses a simple low-temperature hydrothermal process to successfully manufacture ZnInS (m = 1-3) (ZnInS, ZnInS and ZnInS). Incorporating both experimental and theoretical analyses, the structural contraction and local polarization of the Zn-S bond in ZnInS enhance the piezoelectric response and surface charge accumulation, which facilitate charge transfer and reduce the activation energy of water. Remarkably, ZnInS exhibits excellent piezoelectric photocatalytic total water splitting performance (H/O: 4284.72/1967.00 μmol gh), which is 1.77 times that of photocatalytic performance. Moreover, a significant enhancement in DO splitting performance can be obtained for the optimized ZnInS. Our work offers valuable insights into the disclosure of local polarization in catalysts for enhancing piezo-photocatalytic overall water splitting.
PubMed: 38579390
DOI: 10.1016/j.jcis.2024.03.199 -
Journal of Animal Science Jan 2024The aim of the present study was to determine the optimal concentration of dietary protein required in transition diets for multiparous sows that enhance the farrowing...
The aim of the present study was to determine the optimal concentration of dietary protein required in transition diets for multiparous sows that enhance the farrowing process, colostrum production, and subsequent lactation performance. Forty-eight multiparous sows were allotted to one of six dietary treatments according to body weight (290 ± 3 kg) and parity (3.8 ± 0.2) from day 108 of gestation until 24 h after the onset of farrowing. The diets were isoenergetic and contained increasing concentrations of dietary protein (expressed as standardized ileal digestible [SID] Lys) and were supplied at a daily feed supply of 3.8 kg. On day 108 of gestation and days 2, 7, 14, 21, and 28 of lactation, body weight, and back fat thickness were recorded, and blood was sampled on day 108 of gestation, at the onset of farrowing, and days 3, 10, 17, and 24 of lactation from the sows for analysis of plasma metabolites. On day 115 of gestation, urine, and feces were collected for nitrogen (N) balance. The number of liveborn and stillborn piglets and time of birth were recorded and blood from every fourth piglet was sampled at birth for blood gas analysis. Piglets were weighed individually from birth until weaning, to estimate the colostrum and milk yield of the sows. Colostrum and milk samples were collected, and their compositions were determined. On days 3 and 28 of lactation, sows were injected with deuterium oxide to estimate body composition. The N utilization was maximized when the concentration of SID Lys in the transition diet was 6.06 g/kg (P < 0.01). When urinary concentrations of urea were expressed relative to creatinine, the relative concentration of urea remained low until a dietary concentration of 6.08 g SID Lys/kg, above which the relative concentration of urea increased (P < 0.01). Stillbirth rate increased linearly with increasing SID Lys concentration in the transition diet (P < 0.001), thus the concentration of SID Lys should be kept as low as possible without impairing sow performance excessively. A carry-over effect on milk yield was observed, showing that a dietary SID Lys concentration of 5.79 g/kg during transition optimized milk production at an average yield of 13.5 kg/d (P = 0.04). Increasing loss of body fat in lactation was observed with increasing SID Lys concentration in the transition diet (P = 0.03). In conclusion, the transition diet of multiparous sows should contain 5.79 g SID Lys/kg when fed 3.8 kg/d (13.0 MJ ME/kg), for a total SID Lys intake of 22 g/d.
Topics: Pregnancy; Animals; Swine; Female; Diet; Lactation; Body Weight; Dietary Proteins; Urea; Animal Feed
PubMed: 38517473
DOI: 10.1093/jas/skae082 -
Journal of Biomolecular NMR Mar 2024We present an economic and straightforward method to introduce C-F spin systems into the deuterated aromatic side chains of phenylalanine as reporters for various...
We present an economic and straightforward method to introduce C-F spin systems into the deuterated aromatic side chains of phenylalanine as reporters for various protein NMR applications. The method is based on the synthesis of [4-C, 2,3,5,6-H] 4-fluorophenylalanine from the commercially available isotope sources [2-C] acetone and deuterium oxide. This compound is readily metabolized by standard Escherichia coli overexpression in a glyphosate-containing minimal medium, which results in high incorporation rates in the corresponding target proteins.
PubMed: 38509441
DOI: 10.1007/s10858-024-00440-z -
Carbohydrate Polymers Jun 2024Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity....
Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity. In this study, the major polysaccharide fraction, CPP-3a, in Chlorella pyrenoidosa, was isolated, and its detailed structure was investigated by analyzing the low-molecular-weight product prepared via free radical depolymerization. The results indicated that CPP-3a with a molecular weight of 195.2 kDa was formed by →2)-α-L-Araf-(1→, →2)-α-D-Rhap-(1→, →5)-α-L-Araf-(1→, →3)-β-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, →2,3)-α-D-Manp-(1→, →3,4)-α-D-Manp-(1→, →3,4)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and →2,3,6)-α-D-Galp-(1→ residues, branched at C2, C3, C4, or C6 of α/β-D-Galp and α-D-Manp, and terminated by α/β-L-Araf, α-L-Arap, α-D-Galp, and β-D-Glcp. Biological assays showed that CPP-3a significantly altered the dendritic morphology of immature dendritic cells (DCs). Enhanced CD80, CD86, and MHC I expression on the cell surface and decreased phagocytic ability indicated that CPP-3a could induce the maturation of DCs. Furthermore, CPP-3a-stimulated DCs not only stimulated the proliferation of allogeneic naïve CD4 T cells and the secretion of IFN-γ, but also directly stimulated the activation and proliferation of CD8 T cells through cross-antigen presentation. These findings indicate that CPP-3a can promote human DC maturation and T-cell stimulation and may be a novel DC maturation inducer with potential developmental value in DC immunotherapy.
Topics: Humans; Chlorella; CD8-Positive T-Lymphocytes; Polysaccharides; Molecular Weight; Dendritic Cells
PubMed: 38494209
DOI: 10.1016/j.carbpol.2024.122000 -
Proceedings of the National Academy of... Mar 2024Water microdroplets (7 to 11 µm average diameter, depending on flow rate) are sprayed in a closed chamber at ambient temperature, whose relative humidity (RH) is...
Water microdroplets (7 to 11 µm average diameter, depending on flow rate) are sprayed in a closed chamber at ambient temperature, whose relative humidity (RH) is controlled. The resulting concentration of ROS (reactive oxygen species) formed in the microdroplets, measured by the amount of hydrogen peroxide (HO), is determined by nuclear magnetic resonance (NMR) and by spectrofluorimetric assays after the droplets are collected. The results are found to agree closely with one another. In addition, hydrated hydroxyl radical cations (•OH-HO) are recorded from the droplets using mass spectrometry and superoxide radical anions (•O) and hydroxyl radicals (•OH) by electron paramagnetic resonance spectroscopy. As the RH varies from 15 to 95%, the concentration of HO shows a marked rise by a factor of about 3.5 in going from 15 to 50%, then levels off. By replacing the HO of the sprayed water with deuterium oxide (DO) but keeping the gas surrounding droplets with HO, mass spectrometric analysis of the hydrated hydroxyl radical cations demonstrates that the water in the air plays a dominant role in producing HO and other ROS, which accounts for the variation with RH. As RH increases, the droplet evaporation rate decreases. These two facts help us understand why viruses in droplets both survive better at low RH values, as found in indoor air in the wintertime, and are disinfected more effectively at higher RH values, as found in indoor air in the summertime, thus explaining the recognized seasonality of airborne viral infections.
PubMed: 38489384
DOI: 10.1073/pnas.2315940121 -
Nano Letters Mar 2024The deuteration of organic molecules is considerably important in organic and medicinal chemistry. An electrochemical membrane reactor using proton-conducting graphene...
The deuteration of organic molecules is considerably important in organic and medicinal chemistry. An electrochemical membrane reactor using proton-conducting graphene oxide (GO) nanosheets was developed to synthesize valuable deuterium-labeled products via an efficient hydrogen-to-deuterium (H/D) exchange under mild conditions at ambient temperature and atmospheric pressure. Deuterons (D) formed by the anodic oxidation of heavy water (DO) at the Pt/C anode permeate through the GO membrane to the Pt/C cathode, where organic molecules with functional groups (C≡C and C═O) are deuterated with adsorbed atomic D species. Deuteration occurs in outstanding yields with high levels of D incorporation. We also achieved the electrodeuteration of a drug molecule, ibuprofen, demonstrating the promising feasibility of the GO membrane reactor in the pharmaceutical industry.
PubMed: 38489112
DOI: 10.1021/acs.nanolett.3c04243 -
International Journal of Molecular... Mar 2024Liquid chromatography with mass spectrometry (LC-MS)-based metabolomics detects thousands of molecular features (retention time-/ pairs) in biological samples per...
Liquid chromatography with mass spectrometry (LC-MS)-based metabolomics detects thousands of molecular features (retention time-/ pairs) in biological samples per analysis, yet the metabolite annotation rate remains low, with 90% of signals classified as unknowns. To enhance the metabolite annotation rates, researchers employ tandem mass spectral libraries and challenging in silico fragmentation software. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) may offer an additional layer of structural information in untargeted metabolomics, especially for identifying specific unidentified metabolites that are revealed to be statistically significant. Here, we investigate the potential of hydrophilic interaction liquid chromatography (HILIC)-HDX-MS in untargeted metabolomics. Specifically, we evaluate the effectiveness of two approaches using hypothetical targets: the post-column addition of deuterium oxide (DO) and the on-column HILIC-HDX-MS method. To illustrate the practical application of HILIC-HDX-MS, we apply this methodology using the in silico fragmentation software MS-FINDER to an unknown compound detected in various biological samples, including plasma, serum, tissues, and feces during HILIC-MS profiling, subsequently identified as -acetylspermidine.
Topics: Deuterium; Chromatography, Liquid; Metabolomics; Hydrogen Deuterium Exchange-Mass Spectrometry; Hydrophobic and Hydrophilic Interactions
PubMed: 38474147
DOI: 10.3390/ijms25052899 -
Journal of Biomaterials Science.... Jun 2024Recently, we applied solution H-nuclear magnetic resonance spectroscopy (H NMR) to analyze the water (deuterium oxide, DO) structure in several biopolymers at ambient...
Recently, we applied solution H-nuclear magnetic resonance spectroscopy (H NMR) to analyze the water (deuterium oxide, DO) structure in several biopolymers at ambient temperature. We established that polymers with good blood compatibility (i.e. poly(2-methoxyethyl acrylate) (PMEA)) have water observed at high magnetic fields (upfield) compared with bulk water. Polymers containing poly(propylene glycol) (PPG) or poly(propylene oxide) (PPO) exhibit good compatibility; however, the reason for this remains unclear. In addition, reports on the blood compatibility of PPO/PPG are limited. Therefore, PPG diester (PPGest) was prepared as a model polymer, and its blood compatibility and water structure were investigated. PPGest exhibited excellent blood compatibility. The water in PPGest was observed upfield by H NMR, and it was defined as non-freezing water differential scanning calorimetry. Based on these observations, the relationship between the blood compatibility and water structure of PPGest is discussed by comparing with those of PMEA, and the reason for the good performance of PPG/PPO-based polymers is discussed.
Topics: Magnetic Resonance Spectroscopy; Propylene Glycols; Water; Calorimetry, Differential Scanning; Humans; Biocompatible Materials; Materials Testing; Polymers; Animals
PubMed: 38457333
DOI: 10.1080/09205063.2024.2324505