The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Metabolic deuterium oxide (D2O) labeling in quantitative omics studies: A tutorial review.

Mass spectrometry (MS) is an invaluable tool for sensitive detection and characterization of individual biomolecules in omics studies. MS combined with stable isotope labeling enables the accurate and precise determination of quantitative changes occurring in biological samples. Metabolic isotope labeling, wherein isotopes are introduced into biomolecules through biosynthetic metabolism, is one of the main labeling strategies. Among the precursors employed in metabolic isotope labeling, deuterium oxide (D2O) is cost-effective and easy to implement in any biological systems. This tutorial review aims to explain the basic principle of D2O labeling and its applications in omics research. D2O labeling incorporates D into stable C-H bonds in various biomolecules, including nucleotides, proteins, lipids, and carbohydrates. Typically, D2O labeling is performed at low enrichment of 1%-10% D2O, which causes subtle changes in the isotopic distribution of a biomolecule, instead of the complete separation between labeled and unlabeled samples in a mass spectrum. D2O labeling has been employed in various omics studies to determine the metabolic flux, turnover rate, and relative quantification. Moreover, the advantages and challenges of D2O labeling and its future prospects in quantitative omics are discussed. The economy, versatility, and convenience of D2O labeling will be beneficial for the long-term omics studies for higher organisms.

Integrated multi-omics analysis reveals the underlying molecular mechanism for developmental neurotoxicity of perfluorooctanesulfonic acid in zebrafish.

Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1-20 µM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 µM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.

High-Throughput Measurement of Lipid Turnover Rates Using Partial Metabolic Heavy Water Labeling.

Novel analytical platforms for high-throughput determination of lipid turnover in vivo have been developed based on partial metabolic 2H2O labeling. The performance on lipid kinetics measurement of our methods was validated in three different liquid chromatography-mass spectrometry (LC-MS) setups: MS-only, untargeted MS/MS, and targeted MS/MS. The MS-only scheme consisted of multiple LC-MS runs for quantification of lipid mass isotopomers and an extra LC-MS/MS run for lipid identification. The untargeted MS/MS format utilized multiple data-dependent LC-MS/MS runs for both quantification of lipid mass isotopomers and lipid identification. An in-house software was also developed to streamline the data processing from peak area quantification of mass isotopomers to exponential curve fitting for extracting the turnover rate constant. With HeLa cells cultured in 5% 2H2O media for 48 h, we could deduce the species-level turnover rates of 108 and 94 lipids in the MS-only and untargeted MS/MS schemes, respectively, which covers 13 different subclasses and spans 3 orders of magnitude. Furthermore, the targeted MS/MS setup, which performs scheduled LC-MS/MS experiments for some targeted lipids, enabled differential measurement between the turnover rates of the head and tail groups of lipid. The reproducibility of our lipid kinetics measurement was also demonstrated with lipids that commonly detected in both positive and negative ion modes or in two different adduct forms.

Theoretical Prediction of Surface Stability and Morphology of LiNiO2 Cathode for Li Ion Batteries.

Ni-rich layered oxides are considered to be a promising cathode material with high capacity, and their surface structure should be extensively explored to understand the complex associated phenomena. We investigated the surface stability and morphology of LiNiO2 as a representative of these materials by using density functional theory calculations. The results reveal that the Li-exposed surfaces have lower energies than the oxygen surfaces, irrespective of the facets, and the Ni-exposed ones are the least stable. The equilibrium morphology can vary from truncated trigonal bipyramid to truncated egg shape, according to the chemical potential, whose range is confined by the phase diagram. Moreover, the electrochemical window of stable facets is found to strongly depend on the surface elements rather than the facet directions. Contrary to the stable Li surfaces, oxygen exposure on the surface considerably lowers the Fermi level to the level of electrolyte, thereby accelerating oxidative decomposition of the electrolyte on the cathode surface.

Improved electrochemical properties of LiNi0.91Co0.06Mn0.03O2 cathode material via Li-reactive coating with metal phosphates.

Ni-rich layered oxides are promising cathode materials due to their high capacities. However, their synthesis process retains a large amount of Li residue on the surface, which is a main source of gas generation during operation of the battery. In this study, combined with simulation and experiment, we propose the optimal metal phosphate coating materials for removing residual Li from the surface of the Ni-rich layered oxide cathode material LiNi0.91Co0.06Mn0.03O2. First-principles-based screening process for 16 metal phosphates is performed to identify an ideal coating material that is highly reactive to Li2O. By constructing the phase diagram, we obtain the equilibrium phases from the reaction of coating materials and Li2O, based on a database using a DFT hybrid functional. Experimental verification for this approach is accomplished with Mn3(PO4)2, Co3(PO4)2, Fe3(PO4)2, and TiPO4. The Li-removing capabilities of these materials are comparable to the calculated results. In addition, electrochemical performances up to 50 charge/discharge cycles show that Mn-, Co-, Fe-phosphate materials are superior to an uncoated sample in terms of preventing capacity fading behavior, while TiPO4 shows poor initial capacity and rapid reduction of capacity during cycling. Finally, Li-containing equilibrium phases examined from XRD analysis are in agreement with the simulation results.

Computational Screening for Design of Optimal Coating Materials to Suppress Gas Evolution in Li-Ion Battery Cathodes.

Ni-rich layered oxides are attractive materials owing to their potentially high capacity for cathode applications. However, when used as cathodes in Li-ion batteries, they contain a large amount of Li residues, which degrade the electrochemical properties because they are the source of gas generation inside the battery. Here, we propose a computational approach to designing optimal coating materials that prevent gas evolution by removing residual Li from the surface of the battery cathode. To discover promising coating materials, the reactions of 16 metal phosphates (MPs) and 45 metal oxides (MOs) with the Li residues, LiOH, and Li2CO3 are examined within a thermodynamic framework. A materials database is constructed according to density functional theory using a hybrid functional, and the reaction products are obtained according to the phases in thermodynamic equilibrium in the phase diagram. In addition, the gravimetric efficiency is calculated to identify coating materials that can eliminate Li residues with a minimal weight of the coating material. Overall, more MP and MO materials react with LiOH than with Li2CO3. Specifically, MPs exhibit better reactivity to both Li residues, whereas MOs react more with LiOH. The reaction products, such as Li-containing phosphates or oxides, are also obtained to identify the phases on the surface of a cathode after coating. On the basis of the Pareto-front analysis, P2O5 could be an optimal material for the reaction with both Li residuals. Finally, the reactivity of the coating materials containing 3d/4d transition metal elements is better than that of materials containing other types of elements.

Re-construction layer effect of LiNi0.8Co0.15Mn0.05O2 with solvent evaporation process.

The solvent evaporation method on the structural changes and surface chemistry of the cathode and the effect of electrochemical performance of Li1.0Ni0.8Co0.15Mn0.05O2 (NCM) has been investigated. After dissolving of Li residuals using minimum content of solvent in order to minimize the damage of pristine material and the evaporation time, the solvent was evaporated without filtering and remaining powder was re-heated at 700 °C in oxygen environment. Two kinds of solvent, de-ionized water and diluted nitric acid, were used as a solvent. The almost 40% of Li residuals were removed using solvent evaporation method. The NCM sample after solvent evaporation process exhibited an increase in the initial capacity (214.3 mAh/g) compared to the pristine sample (207.4 mAh/g) at 0.1C because of enhancement of electric conductivity caused by decline of Li residuals. The capacity retention of NCM sample after solvent evaporation process (96.0% at the 50th cycle) was also improved compared to that of the pristine NCM sample (90.6% at the 50th cycle). The uniform Li residual layer after solvent treated and heat treatment acted like a coating layer, leading to enhance the cycle performance. The NCM sample using diluted nitric acid showed better performance than that using de-ionized water.

A first-principles study of the preventive effects of Al and Mg doping on the degradation in LiNi0.8Co0.1Mn0.1O2 cathode materials.

First-principles calculations have been used to investigate the effects of Al and Mg doping on the prevention of degradation phenomena in Li(Ni0.8Co0.1Mn0.1)O2 cathode materials. Specifically, we have examined the effects of dopants on the suppression of oxygen evolution and cation disordering, as well as their correlation. It is found that Al doping can suppress the formation of oxygen vacancies effectively, while Mg doping prevents the cation disordering behaviors, i.e., excess Ni and Li/Ni exchange, and Ni migration. This study also demonstrates that formation of oxygen vacancies can facilitate the construction of the cation disordering, and vice versa. Delithiation can increase the probabilities of formation of all defect types, especially oxygen vacancies. When oxygen vacancies are present, Ni can migrate to the Li site during delithiation. However, Al and Mg doping can inhibit Ni migration, even in structures with preformed oxygen defects. The analysis of atomic charge variations during delithiation demonstrates that the degree of oxidation behavior in oxygen atoms is alleviated in the case of Al doping, indicating the enhanced oxygen stability in this structure. In addition, changes in the lattice parameters during delithiation are suppressed in the Mg-doped structure, which suggests that Mg doping may improve the lattice stability.

Enhancement in the electrochemical performance of zirconium/phosphate bi-functional coatings on LiNi0.8Co0.15Mn0.05O2 by the removal of Li residuals.

The effect of bi-functional coatings consisting of Zr and phosphate (P) on the electrochemical performance of Li1.0Ni0.8Co0.15Mn0.05O2 (NCM) has been investigated. The presence of various types of Zr and P compounds such as oxides (ZrO2 and Li2ZrO3) and phosphates (Zr2P2O9, ZrP2O7 and LiZr2(PO4)3) in the coating was confirmed by experiments as well as density functional theory (DFT) calculations. When the NCM samples were coated with the Zr/P hybrid material, the cycle retention and the amount of removed Li residuals (LiOH, Li2CO3) were enhanced by the synergistic effect from Zr and P. The NCM sample coated with a Zr/P layer with a Zr/P ratio of 1 : 1 exhibited an increase in the initial capacity (209.3 mA h g-1) compared to the pristine sample (207.4 mA h g-1) at 0.1C, owing to the formation of the coating layer. The capacity retention of the Zr/P coated sample (92.4% at the 50th cycle) was also improved compared to that of the pristine NCM sample (90.6% at the 50th cycle). Moreover, the amount of Li residuals in the Zr/P coated NCM sample was greatly reduced from 3693 ppm (pristine NCM) to 2525 ppm (Zr/P = 5 : 5).

Effects of Lithium Oxide Addition on Sintering Behavior and Electrical Conductivity of Ce0.8Gd0.2O1.9 Ceramics Prepared by Commercial Powders.

The densification behavior and electrical conductivity of Ce0.8Gd0.2O1.9 ceramics with lithium oxide concentrations ranging from 0 to 7 mol% were investigated. The sintered density was found to increase with increasing Li2O content up to 2 mol% and then to decrease somewhat upon further Li20 addition. Dense Ce0.8Gd0.2O1.9 ceramics with 97% of the theoretical density could be obtained by sintering the milled mixture with 2 mol% Li2O addition at 1250 degrees C for 5 h. The conductivity of the 2 mol% Li2O-added specimen showed a maximum value of 4.99 x 10(-3) Ω(-1) x cm(-1) at 700 degrees C. Pure Ce0.8Gd0.2O1.9 ceramics needed to be sintered at 1550 degrees C in order to obtain an equivalent theoretical density and conductivity. The addition of Li2O was found to promote the sintering properties and electrical conductivities of Gd2O3-doped CeO2.

Flight Test Result for the Ground-Based Radio Navigation System Sensor with an Unmanned Air Vehicle.

The Ground-based Radio Navigation System (GRNS) is an alternative/backup navigation system based on time synchronized pseudolites. It has been studied for some years due to the potential vulnerability issue of satellite navigation systems (e.g., GPS or Galileo). In the framework of our study, a periodic pulsed sequence was used instead of the randomized pulse sequence recommended as the RTCM (radio technical commission for maritime services) SC (special committee)-104 pseudolite signal, as a randomized pulse sequence with a long dwell time is not suitable for applications requiring high dynamics. This paper introduces a mathematical model of the post-correlation output in a navigation sensor, showing that the aliasing caused by the additional frequency term of a periodic pulsed signal leads to a false lock (i.e., Doppler frequency bias) during the signal acquisition process or in the carrier tracking loop of the navigation sensor. We suggest algorithms to resolve the frequency false lock issue in this paper, relying on the use of a multi-correlator. A flight test with an unmanned helicopter was conducted to verify the implemented navigation sensor. The results of this analysis show that there were no false locks during the flight test and that outliers stem from bad dilution of precision (DOP) or fluctuations in the received signal quality.

Wavelength-division-multiplexing optical packet switch with heterogeneous wavelength conversion capabilities.

Among the wavelength-division-multiplexing (WDM) optical packet switches (OPSs) using wavelength converters (WCs), a shared-per-node switch architecture has been considered as a way to utilize WCs efficiently. We propose a new switch control algorithm for the architecture. The proposed algorithm, different from previous algorithms, focuses on using the heterogeneous WC blocks (HeWCBs), where a HeWCB consists of WCs with different wavelength conversion degrees (WCDs). The results show that the WDM OPS architecture using HeWCBs reduces the number of WCs with a higher WCD, while minimizing the packet loss from wavelength contention at outbound links.

Frequency-hopping optical orthogonal codes with arbitrary time-blank patterns.

We investigate a general scheme of frequency-hopping optical orthogonal codes with a specified distance between adjacent frequency symbols and propose a novel code that allows time blanks between adjacent frequency symbols in code sequences. A time blank represents the absence of frequency symbols in code sequences and makes no interference with frequency components. The insertion of time-blank patterns can provide ample scope to generate much more code sequences than the conventional codes lacking in time-blank patterns, and we show this by constructing an algorithm to generate the proposed code. The performance analysis demonstrates that its performance is superior to that of the conventional codes in terms of the bit error rate. We also derive the upper bound on the proposed code set.